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Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime
MUST WE AGE?
A long life in a healthy, vigorous, youthful body has always been one of humanity's greatest dreams. Recent progress in genetic manipulations and calorie-restricted diets in laboratory animals hold forth the promise that someday science will enable us to exert total control over our own biological aging.
Nearly all scientists who study the biology of aging agree that we will someday be able to substantially slow down the aging process, extending our productive, youthful lives. Dr. Aubrey de Grey is perhaps the most bullish of all such researchers. As has been reported in media outlets ranging from 60 Minutes to The New York Times, Dr. de Grey believes that the key biomedical technology required to eliminate aging-derived debilitation and death entirely--technology that would not only slow but periodically reverse age-related physiological decay, leaving us biologically young into an indefinite future--is now within reach.
In Ending Aging, Dr. de Grey and his research assistant Michael Rae describe the details of this biotechnology. They explain that the aging of the human body, just like the aging of man-made machines, results from an accumulation of various types of damage. As with man-made machines, this damage can periodically be repaired, leading to indefinite extension of the machine's fully functional lifetime, just as is routinely done with classic cars. We already know what types of damage accumulate in the human body, and we are moving rapidly toward the comprehensive development of technologies to remove that damage. By demystifying aging and its postponement for the nonspecialist reader, de Grey and Rae systematically dismantle the fatalist presumption that aging will forever defeat the efforts of medical science.
A long life in a healthy, vigorous, youthful body has always been one of humanity's greatest dreams. Recent progress in genetic manipulations and calorie-restricted diets in laboratory animals hold forth the promise that someday science will enable us to exert total control over our own biological aging.
Nearly all scientists who study the biology of aging agree that we will someday be able to substantially slow down the aging process, extending our productive, youthful lives. Dr. Aubrey de Grey is perhaps the most bullish of all such researchers. As has been reported in media outlets ranging from 60 Minutes to The New York Times, Dr. de Grey believes that the key biomedical technology required to eliminate aging-derived debilitation and death entirely--technology that would not only slow but periodically reverse age-related physiological decay, leaving us biologically young into an indefinite future--is now within reach.
In Ending Aging, Dr. de Grey and his research assistant Michael Rae describe the details of this biotechnology. They explain that the aging of the human body, just like the aging of man-made machines, results from an accumulation of various types of damage. As with man-made machines, this damage can periodically be repaired, leading to indefinite extension of the machine's fully functional lifetime, just as is routinely done with classic cars. We already know what types of damage accumulate in the human body, and we are moving rapidly toward the comprehensive development of technologies to remove that damage. By demystifying aging and its postponement for the nonspecialist reader, de Grey and Rae systematically dismantle the fatalist presumption that aging will forever defeat the efforts of medical science.
389 pages, Hardcover
First published January 1, 2007
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Displaying 1 - 30 of 83 reviews
January 27, 2009
I had been wondering about the legitimacy of the idea of radical life extension, and was lead to this book. De Gray is a gerontologist - he does basic research into the causes of aging related diseases - and his stated purpose in writing this book is to encourage the public to view aging as a treatable disease rather than an inevitable part of the cycle of life and death.
The book consists of a short moral argument about the immediate importance of researching aging (because it maims and kills huge numbers of people everyday), a survey of seven of the most significant known causes of human aging, and what is known about how those causes can be addressed and combated. Were talking a much deeper level than "eat healthy and exercise" sort of advice; de Gray's main line of research is into mutations in mitochondrial DNA that cause increased cell stress via production of free-radicals. In other words: something that will need to be addressed in a lab rather than your kitchen.
That leads to the other key reason for the book's existence: to encourage funding into these kinds of research. His stance is that we know what research needs to be done to literally end aging; how quickly the research gets funded and accomplished will determine how many people can be saved from painful deaths. He does calls for governments to fund this research in the same way they fund research into cancer and aids, and argues that the payoff will be greater. But I really enjoy his contest-focused approach to fund raising: his foundation (the Methuselah Foundation) has set up a prize for a few key milestones to encourage people and institutions to undertake the research. This is the same concept as the X-prize (which is also privately funded); the idea is that the presence of a contest lends legitimacy to a course of research that might otherwise seem too risky. Organizations are thus able to get financing for cutting edge things, and much more money gets invested into the project than would have been had it been controlled by some government agency.
The book is wonderful in its passionate sense of urgency, and in its gentle (but satisfyingly technical and difficult) presentation of some very deep concepts in cellular and molecular biology. It would be a great book to give to someone who's interested in studying medicine, but hasn't yet decided exactly what field they'd like to become an expert in.
The book consists of a short moral argument about the immediate importance of researching aging (because it maims and kills huge numbers of people everyday), a survey of seven of the most significant known causes of human aging, and what is known about how those causes can be addressed and combated. Were talking a much deeper level than "eat healthy and exercise" sort of advice; de Gray's main line of research is into mutations in mitochondrial DNA that cause increased cell stress via production of free-radicals. In other words: something that will need to be addressed in a lab rather than your kitchen.
That leads to the other key reason for the book's existence: to encourage funding into these kinds of research. His stance is that we know what research needs to be done to literally end aging; how quickly the research gets funded and accomplished will determine how many people can be saved from painful deaths. He does calls for governments to fund this research in the same way they fund research into cancer and aids, and argues that the payoff will be greater. But I really enjoy his contest-focused approach to fund raising: his foundation (the Methuselah Foundation) has set up a prize for a few key milestones to encourage people and institutions to undertake the research. This is the same concept as the X-prize (which is also privately funded); the idea is that the presence of a contest lends legitimacy to a course of research that might otherwise seem too risky. Organizations are thus able to get financing for cutting edge things, and much more money gets invested into the project than would have been had it been controlled by some government agency.
The book is wonderful in its passionate sense of urgency, and in its gentle (but satisfyingly technical and difficult) presentation of some very deep concepts in cellular and molecular biology. It would be a great book to give to someone who's interested in studying medicine, but hasn't yet decided exactly what field they'd like to become an expert in.
May 12, 2011
The science is fascinating, but de Grey's ego can be a distraction.
April 14, 2017
Aubrey de Grey provides an optimistic service in summarizing all aging into seven general physiological areas, and providing a framework for science-based rejuvenation: strategies for engineering negligible senescence (SENS). Each area includes rather detailed biochemical and physiological explanations, and an evaluation of progress from related medical work.
The 7 areas are:
Mitochondrial DNA failures
Cell loss/atrophy, incl Immune senescence
Cancer
Death avoiding cells
Intercellular junk, and lysosome overload
Extracellular junk, including glyciated proteins
Cross linking of proteins, including tau/Alzheimers
He makes a smart, essential distinction between preventative and palliative treatments, versus rejuvenating or curative treatment. Aging damage will inevitably accumulate, so masking or slowing it, alone, is insufficient to extend life dramatically.
Unfortunately, de Grey is now more of a fundraiser and cheerleader, and I can't tell how true are his scientific assertions and prognostications. I am not sure why he seems so isolated, but clearly that won't work in medicine.
He likes naming things and seems to insist on leading things, perhaps because he's sure his ideas are the best. The book is too heavy on his own discoveries and theories, without full focus on how to actually achieve SENS given the entire universe of available ideas and contributors.
This book is 10-12 years old, and it seems he has made very little progress sense. Four stars for biomedical detail in clear explanations, and memorably teaching valuable vocabulary, though it is verbose and repetitive.
The example of where he suggests solving visceral fat by ordering those cells to apoptosis, using the fact that they tend to be older, makes me think he isn't as reliable as his command of pure vocabulary indicates. As does his tired, trite blaming of "politics".
The book gets 4 stars, as provocative and informative; the author/messenger gets 2 stars in my mind.
The 7 areas are:
Mitochondrial DNA failures
Cell loss/atrophy, incl Immune senescence
Cancer
Death avoiding cells
Intercellular junk, and lysosome overload
Extracellular junk, including glyciated proteins
Cross linking of proteins, including tau/Alzheimers
He makes a smart, essential distinction between preventative and palliative treatments, versus rejuvenating or curative treatment. Aging damage will inevitably accumulate, so masking or slowing it, alone, is insufficient to extend life dramatically.
Unfortunately, de Grey is now more of a fundraiser and cheerleader, and I can't tell how true are his scientific assertions and prognostications. I am not sure why he seems so isolated, but clearly that won't work in medicine.
He likes naming things and seems to insist on leading things, perhaps because he's sure his ideas are the best. The book is too heavy on his own discoveries and theories, without full focus on how to actually achieve SENS given the entire universe of available ideas and contributors.
This book is 10-12 years old, and it seems he has made very little progress sense. Four stars for biomedical detail in clear explanations, and memorably teaching valuable vocabulary, though it is verbose and repetitive.
The example of where he suggests solving visceral fat by ordering those cells to apoptosis, using the fact that they tend to be older, makes me think he isn't as reliable as his command of pure vocabulary indicates. As does his tired, trite blaming of "politics".
The book gets 4 stars, as provocative and informative; the author/messenger gets 2 stars in my mind.
January 10, 2025
Romanian review: Am întâlnit pentru prima dată conceptul unei lumi în care oamenii nu îmbătrânesc într-un videoclip făcut de Kurzgesagt. De atunci, ideea unei vieți care se întinde pe termen nedeterminat m-a fascinat. Am reîntâlnit conceptul în Sapiens - O scurtă istorie a omenirii și, într-un final, am găsit o carte care să abordeze subiectul în detaliu. "Ending Aging" este una dintre cele mai fascinante cărți pe care le-am citit vreodată.
Aubrey de Grey a reușit, în câteva sute de pagini, să sintetizeze toată informația necesară pentru a înțelege exact procesul de îmbătrânire și deteriorările care se acumulează de-a lungul vieții la nivel celular. El le împarte în șapte categorii și prezintă, într-un mod accesibil, felul în care acestea pot fi înlăturate, cu scopul final de-a le permite oamenilor să devină aproape nemuritori.
Ideea în sine că am putea să învingem moartea sună ca un concept științifico-fantastic, iar Aubrey de Grey nu se ferește din a prezenta toate complicațiile planului său de-a opri îmbătrânirea, admițând că unele strategii sunt extrem de ambițioase și că este nevoie de mult mai multă cercetare în domeniu, prezentând în detaliu neajunsurile războiului împotriva îmbătrânirii. Practic, au trecut 15 ani de când cartea a fost publicată și nu am făcut nici pe departe progresele la care spera autorul.
Este adevărat că, pe lângă dorința de a convinge cititorii că moartea nu este un aspect inevitabil al realității noastre, unul dintre scopurile cărții este finanțarea fundației lui de Grey, prin urmare, cartea trebuie luată cu puțină sare. Dar, per total, aș spune că de Grey este destul de sincer în abordarea sa.
După toate laudele aduse acestei cărți, te vei întreba probabil de ce nu i-am dat cinci stele. Nu i-am dat cinci stele din cauza aroganței autorului care se simte de fiecare dată când prezintă o idee, un concept sau o teorie la care "el s-a gândit înaintea tuturor". Aubrey de Grey este un om orgolios. Dacă orgoliul său este justificat sau nu, asta nu schimbă faptul că știrbește puțin din plăcerea lecturii.
Trecând peste problema egoului lui Aubrey de Grey, informațiile pe care le prezintă sunt fascinante. Abordarea sa este accesibilă, iar "Ending Aging" este o carte care te face să visezi cu ochii deschiși la lumea în care am putea trăi— o lume în care moartea este de domeniul trecutului.
English review: I first encountered the concept of a world where people don’t age in a video by Kurzgesagt. Since then, the idea of a life that extends indefinitely has fascinated me. I revisited the concept in Sapiens: A Brief History of Humankind and, finally, found a book that delves deeply into the subject. "Ending Aging" is one of the most fascinating books I’ve ever read.
Aubrey de Grey has managed, in just a few hundred pages, to synthesize all the information necessary to fully understand the aging process and the cellular damage that accumulates throughout life. He categorizes these damages into seven types and presents, in an accessible way, how they can be eliminated with the ultimate goal of enabling humans to become nearly immortal.
The very idea that we could conquer death sounds like a science fiction concept, and Aubrey de Grey does not shy away from presenting all the complications of his plan to halt aging. He openly admits that some strategies are extremely ambitious and that much more research is needed in the field. He thoroughly discusses the shortcomings of the battle against aging. In fact, it has been 15 years since the book was published, and we are far from achieving the progress de Grey hoped for.
It’s true that, alongside his aim to convince readers that death is not an inevitable aspect of our reality, one of the book's goals is to fundraise for de Grey’s foundation. Therefore, the book should be taken with a grain of salt. However, I would say that de Grey is fairly transparent in his approach overall.
After all this praise for the book, you might be wondering why I didn’t give it five stars. I held back from giving it the highest rating because of the author’s arrogance, which becomes apparent whenever he presents an idea, concept, or theory that "he thought of before anyone else." Aubrey de Grey is a proud man. Whether his pride is justified or not doesn’t change the fact that it slightly detracts from the pleasure of reading.
Setting aside the issue of de Grey’s ego, the information he presents is absolutely fascinating. His approach is accessible, and "Ending Aging" is a book that makes you dream with open eyes about the kind of world we could live in—a world where death is a thing of the past.
February 10, 2014
=D The book describes many various forms of aging and strategies to clean them out or obviate them. I've never really had a biology class, so I found it to be a good primer in that sense too. I've wanted to live forever since I was a kid and never doubted its possibility. So it's very nice to have a general view of how we may actually do this.
One can tell which chapters De Grey knows more about and which he doesn't. The ones he knows the best are far better written.
One can tell which chapters De Grey knows more about and which he doesn't. The ones he knows the best are far better written.
May 21, 2020
Oldie but a goodie. A must-read introductory text for those interested in longevity sciences.
The book is broken down into three parts.
1. A moral argument as to why aging should be the highest disease on our hit-list
2. An explaining of SENS and a detailed biological explanation on how we think we can combat these aspects of aging
3. A rallying closure that urges you to take part.
For me the moral argument of this book is the lynch pin for new readers on the topic of longevity.
Other reviews of this book criticize ADG's ego and I can sympathize with that. The way I see if is that if you already are bought in to the possibility of radical life extensions then the ego will not bother you. However if on the other hand...
The book is broken down into three parts.
1. A moral argument as to why aging should be the highest disease on our hit-list
2. An explaining of SENS and a detailed biological explanation on how we think we can combat these aspects of aging
3. A rallying closure that urges you to take part.
For me the moral argument of this book is the lynch pin for new readers on the topic of longevity.
Other reviews of this book criticize ADG's ego and I can sympathize with that. The way I see if is that if you already are bought in to the possibility of radical life extensions then the ego will not bother you. However if on the other hand...
Read
December 5, 2017"Give me all your pension money, and I'll make sure you live forever!" Yeah, like we hadn't heard that one before. It's written in a fun way, but as a moleculair biologist I was cringing every other page at inconsistenties and misquotations to plain basic science. Would work as a fictional book, not a scientific one. Have a good laugh, and forget about it.
January 2, 2010
read the book, become obsessed with living forever
Read
June 5, 2019I am happy that someone or some people dare to explore this domain. That left me hopeful and excited....
October 29, 2019
I've been wanting to read this book ever since I saw a youtube of the Aubrey de Grey giving a Google authors talk (There's also a fairly good, much shorter TED talk - well, by now, I think there are several). So, I finally did. The book is now 12 years old, and I can't seem to find a video that I'm sure was the original (I know it was at least an hour long, and at the end someone asked a question, "If your goal is to become young, why do you assume the appearance of a very old man?" To which he memorably replied "Because I actually am... a very, VERY old man! ;-))
Anyway, I haven't really kept up with his work in all those years, but I get the impression some progress has been made, I just don't know how much, and I'm not enough of a biologist or medical expert to judge. But, I do feel I learned an immense amount of biology by reading this book, and I really enjoy the optimism of techno-futurists.
Something that occured to me at the end of this book is that, although he is a scientist (has a Ph.D., know lots about research, has probably even done lots of research), at this point, he's at a really high-level of the game where everything is about funding, PR, politics, etc... his goal is to clear away all counter arguments, and focus on relatively easily done research that will be the ultimate clinching argument for why this is possible (and therefore must be pursued) for humans.
So, it's a bit about philosophy (why this is a good thing and not a bad thing), psychology (why people aren't already clamoring for this, and how to make that happen), and ultimately it's about making arguments. This is fundamentally a book of arguments (albeit in a very detailed, and somewhat obscure branch of medical science). I actually love arguments (logically structured debates, that is; NOT heated emotional exchanges). Perhaps that's why I've always found him so unforgettable.
Anyway, I haven't really kept up with his work in all those years, but I get the impression some progress has been made, I just don't know how much, and I'm not enough of a biologist or medical expert to judge. But, I do feel I learned an immense amount of biology by reading this book, and I really enjoy the optimism of techno-futurists.
Something that occured to me at the end of this book is that, although he is a scientist (has a Ph.D., know lots about research, has probably even done lots of research), at this point, he's at a really high-level of the game where everything is about funding, PR, politics, etc... his goal is to clear away all counter arguments, and focus on relatively easily done research that will be the ultimate clinching argument for why this is possible (and therefore must be pursued) for humans.
So, it's a bit about philosophy (why this is a good thing and not a bad thing), psychology (why people aren't already clamoring for this, and how to make that happen), and ultimately it's about making arguments. This is fundamentally a book of arguments (albeit in a very detailed, and somewhat obscure branch of medical science). I actually love arguments (logically structured debates, that is; NOT heated emotional exchanges). Perhaps that's why I've always found him so unforgettable.
September 13, 2021
Aubrey de Grey is the biggest crackpot to ever exist. If you do not believe this review, look him up on google - there is a documentary where his lies are exposed. He is not even a PhD and has only set foot in an institution of higher learning as a school administrator/clerk, not faculty. In this book he presents pseudo-scientific, highly speculative theories which have been proven to be completely impractical and downright impossible scientifically by experts in the field. Here, I'll save you a few hours: He gives you theories, tells you they are not yet possible because the technology isn't there yet and he ends it with - exercise, eat well, and donate to his "research foundation" so he can test out his crack-pot theories. I think the next title of his book should be: "Ending Crack-pottery: How I convinced thousands of people of my crack-pot theories regarding aging". I stopped reading this nonsense after chapter 3. I should've stopped sooner.
Readability: Hard -o--- Easy (quackery disguised as professional medical talk)
Practicality: Low o---- High
Insights: Few o---- Many
Length: Long o---- Short (too long considering its all nonsense)
Overall: Bad o---- Amazing
March 17, 2019
I appreciate Aubrey took the time to write this book. It was meant for a layman. And I know how hard it is to translate scientific knowledge to someone with not-so-science background people. He starts each chapter with interesting metaphors like grilled Turkey on Thanks Giving and our aging. That kept my interest high in the pile of technical jargon.
I also like how Aubrey writes down how he has approached a problem and his thinking process. Obviously, he's an intelligent man. But that type of thinking process is hard to find because they are usually busy doing the actual project.
The book is from 2007, but it will give you a comprehensive understanding of biology in general from aging to cancers. I felt like I caught up a lot in current issues surrounding real world biology.
I also like how Aubrey writes down how he has approached a problem and his thinking process. Obviously, he's an intelligent man. But that type of thinking process is hard to find because they are usually busy doing the actual project.
The book is from 2007, but it will give you a comprehensive understanding of biology in general from aging to cancers. I felt like I caught up a lot in current issues surrounding real world biology.
June 25, 2023
In this book, famous gerontologist Aubrey de Grey gave us an overview of the biological process of aging, as well as the 7 subprocesses that underlie it. Reversing or clearing up the mess caused by each of these processes, should theoretically grant humans hundreds and maybe thousands of years of (youthful) lifespan.
Solving the problem of aging for good, including the tackling of other processes that accumulate damage in the body more slowly, or have yet to be uncovered, would in principle make humans biologically immortal, meaning that unless an individual's attention lapses and they get hit by a bus, or they fall from the top of a cliff, or any such accident that happens too suddenly, quickly or systematically, they should be able to live indefinitely.
The main take-away from this book in my opinion, is that there's nothing magical about aging in humans or other animals, and that we should see it as a hitherto unstoppable (but eventually defeatable) process of decay and accumulation of molecular junk that interferes with normal youthful function. It's the result of complex metabolic and other types of processes, and the fact that the molecular and cellular repair machinery was designed by evolution only to take us long enough to procreate and raise the next generation. There has basically been no selection pressure to allow the human individual to survive past the stage of passing on their genes and perpetuating the species, rather than the self.
The book brings up the famous concept of "longevity escape velocity" (which already existed in other terms within science fiction and the longevity movement, but was coined in these terms by de Grey himself in a 2004 paper). This concept basically means that if an individual lives long enough top catch up with the first radical medical treatments of aging, they should, in principle, be able to live indefinitely, since they will keep surviving to the next round of technological breakthroughs in longevity medicine and have extra years or decades to catch with the breakthrough after, and so on and so forth.
This book has been sitting on my waitlist for more than a decade, ever since I became aware of the transhumanist and longevity movement, and tried to make some (extremely modest) contributions to it with some scattered writings (most of which unworthy of mention). I should have gotten around to it way sooner, but I'm glad I finally did.
I do not know if there will be a follow up to this book, with an update as to the scientific and technological developments that took place since 2008, when this book came out. But I sure hope we are close enough to solving at least some of the underlying problems of aging, which are causing much suffering to the elderly among us. The human metabolism is extremely complex, and not very well understood, but I believe human ingenuity will eventually crack this problem, and that an ageless future will be a reality, maybe for some of us living today, maybe at least for future generations. In the meantime, the common mortal, i.e. all of us right now, should use traditional means to live healthy and hopefully long lives, by eating modertately and healthily, exercising regularly, sleeping well, and generally taking care of our bodies and mental health.
Solving the problem of aging for good, including the tackling of other processes that accumulate damage in the body more slowly, or have yet to be uncovered, would in principle make humans biologically immortal, meaning that unless an individual's attention lapses and they get hit by a bus, or they fall from the top of a cliff, or any such accident that happens too suddenly, quickly or systematically, they should be able to live indefinitely.
The main take-away from this book in my opinion, is that there's nothing magical about aging in humans or other animals, and that we should see it as a hitherto unstoppable (but eventually defeatable) process of decay and accumulation of molecular junk that interferes with normal youthful function. It's the result of complex metabolic and other types of processes, and the fact that the molecular and cellular repair machinery was designed by evolution only to take us long enough to procreate and raise the next generation. There has basically been no selection pressure to allow the human individual to survive past the stage of passing on their genes and perpetuating the species, rather than the self.
The book brings up the famous concept of "longevity escape velocity" (which already existed in other terms within science fiction and the longevity movement, but was coined in these terms by de Grey himself in a 2004 paper). This concept basically means that if an individual lives long enough top catch up with the first radical medical treatments of aging, they should, in principle, be able to live indefinitely, since they will keep surviving to the next round of technological breakthroughs in longevity medicine and have extra years or decades to catch with the breakthrough after, and so on and so forth.
This book has been sitting on my waitlist for more than a decade, ever since I became aware of the transhumanist and longevity movement, and tried to make some (extremely modest) contributions to it with some scattered writings (most of which unworthy of mention). I should have gotten around to it way sooner, but I'm glad I finally did.
I do not know if there will be a follow up to this book, with an update as to the scientific and technological developments that took place since 2008, when this book came out. But I sure hope we are close enough to solving at least some of the underlying problems of aging, which are causing much suffering to the elderly among us. The human metabolism is extremely complex, and not very well understood, but I believe human ingenuity will eventually crack this problem, and that an ageless future will be a reality, maybe for some of us living today, maybe at least for future generations. In the meantime, the common mortal, i.e. all of us right now, should use traditional means to live healthy and hopefully long lives, by eating modertately and healthily, exercising regularly, sleeping well, and generally taking care of our bodies and mental health.
April 25, 2025
um mundo que ainda treme sob o inverno da morte e deterioração relacionadas ao envelhecimento, atiçando as faíscas que devemos transformar em uma grande fogueira que eliminará suas trevas obscurecedoras e derreterá sua garra gelada."
Temos as mutações nos nossos cromossomos, é claro, que causam o câncer; a glicação (a alteração da estrutura das proteínas causada pela glicose); e os vários tipos de lixo que se acumulam fora das células (os “agregados extracelulares”: beta amiloides, a menos conhecida transtirretina e possivelmente outras substâncias do mesmo tipo geral).
mutações mitocondriais, que parecem deteriorar a bioquímica celular ao aumentar o estresse oxidativo.
interligados que contribuem para os danos do envelhecimento. Para criar terapias, tudo que seria necessário entender são os danos em si do envelhecimento: as lesões moleculares e celulares que prejudicam a estrutura e o funcionamento dos tecidos do corpo.
vencer o envelhecimento levará à eliminação deste período, ao adiá- lo para idades indefinidamente maiores de forma que as pessoas nunca cheguem a ele.
a vida não é lógica.
o físico Max Planck fez uma observação há mais de oitenta anos em que dizia que "a ciência avança de funeral em funeral", e o biólogo J. B. S. Haldane disse que "há quatro estágios na aceitação: (I) isso é um absurdo inútil; (II) isso é um ponto de vista interessante, mas errado; (III) isso é verdade, mas é pouco importante; (IV) eu sempre disse isso."
as enfermidades do envelhecimento deveriam ser vistas como separadas em dois fenômenos distintos: de um lado, as doenças relacionadas ao envelhecimento, e do outro, "o envelhecimento em si".
envelhecimento é, nem mais nem menos, o conjunto de estágios iniciais das várias doenças relacionadas ao envelhecimento.
acima: a capacidade natural de autorreparo com a qual nascemos é nossa aliada na cruzada contra o envelhecimento, não nossa inimiga.
Quando uma larva de nematódeo segue o caminho dauer, ela pausa seu desenvolvimento por um período que pode durar muito mais do que a vida inteira de um nematódeo que segue o caminho normal não dauer.
O prolongamento de vida como resposta à privação de nutrientes é simplesmente a expressão da intuição geneticamente programada de um organismo em relação ao grau apropriado de atenção aos detalhes que ele deve exercer em seu funcionamento molecular e celular diário— e, por ser essa sua natureza, ele não é passível de melhorias substanciais através de tecnologias biomédicas no futuro próximo.
terapias de reparação repararão uma determinada quantidade de danos, mas não todos os danos, e as terapias de prevenção desacelerarão mas não interromperão o acúmulo de danos.
Os geriatras tentam ajudar as pessoas cujo envelhecimento chegou num ponto em que as funções físicas ou mentais estão consideravelmente prejudicadas.
Os radicais livres são simplesmente reativos demais para serem varridos com vitaminas,
os radicais livres mitocondriais não impulsionam um aumento sistêmico do estresse oxidativo com a idade por danificar diretamente o resto da célula. Em vez disso, o dano que eles causam ao DNA mitocondrial faz com que a mitocôndria entre em um estado mal- adaptativo que espalha o estresse oxidativo mais além da célula.
Na biologia, radicais livres são, em geral, moléculas à base de oxigênio que perderam um de seus elétrons em relação a sua quantidade normal.
o fato é que a esmagadora maioria dos radicais livres aos quais o corpo é exposto é gerada nas próprias células humanas— nas mitocôndrias, nossas "usinas de energia" celulares.
as mitocôndrias criam resíduos tóxicos durante a conversão de energia de uma forma para outra.
A restrição calórica— a única intervenção não genética que sabidamente diminui a velocidade do envelhecimento em mamíferos— melhora todos esses parâmetros: ela diminui a geração de radicais livres mitocondriais, fortalece as membranas mitocondriais contra o ataque dos radicais livres, e acima de tudo reduz o acúmulo de mutações no DNA mitocondrial relacionado ao envelhecimento (a remoção ou reescrita irreparável de "letras" do livro de instruções genético).
Tanto em pessoas de cinco quanto de cinquenta anos de idade, qualquer mitocôndria em suas células possui membranas e proteínas que têm em média somente algumas semanas de idade. Assim, os componentes mitocondriais mais novos e mais velhos estão presentes na mesma proporção tanto nas pessoas mais velhas quanto nas mais novas. Simplesmente não é possível que o envelhecimento seja impulsionado por um processo progressivo de degeneração de componentes que na realidade sofrem um processo contínuo de renovação.
O envelhecimento é uma doença pandêmica mortal,
A catalase quebra o peróxido de hidrogênio— uma molécula similar aos radicais livres— transformando- o na inofensiva água antes de que possa se tornar mais perigoso e causar sérios danos moleculares.
a desregulação crônica dos caminhos de sinalização das células seria um alto preço a pagar por um menor estresse oxidativo.
"idiomas" do DNA das mitocôndrias e do núcleo da célula desenvolveram "dialetos" ligeiramente diferentes, de forma que uma cópia exata de uma determinada sequência de DNA mitocondrial torna- se indecifrável quando é colocada no núcleo. Este problema chama- se disparidade de código.
gene mitocondrial chamado ND4; as mutações neste gene causam uma mitocondriopatia— a neuropatia óptica hereditária de Leber (LHON).
Inteínas são sequências que são inseridas temporariamente em algumas proteínas logo que são sintetizadas, possivelmente para ajudar a proteína a amadurecer adequadamente até sua forma final, e então são removidas após cumprirem seu propósito.
capacidade de introduzir na mitocôndria versões modificadas, não de genes individuais (como na abordagem clássica da terapia genética), mas de cópias completas do DNA mitocondrial inteiro. Eles conseguiram realizar esse procedimento— que denominaram protofecção
trabalho do lisossomo não é destruir completamente os resíduos celulares, mas decompô- los a nível molecular em componentes mais básicos que podem ser usados como matéria- prima para a biossíntese de novas membranas celulares, enzimas e outros componentes importantes do maquinário celular.
teoria do envelhecimento por "catástrofe de lixo", na qual a lipofuscina que vai se acumulando dentro do lisossomo dilui a acidez da organela e o suprimento de enzimas.
Os pesquisadores tendem a se refugiar em seus campos de estudo estreitamente especializados, e consequentemente eles também raramente trocam informações e observam a confluência de observações em diferentes campos da ciência (ou mesmo em subcampos dentro destes campos).
o trans- retinal pode reagir com algumas moléculas lipídicas que formam a membrana celular, levando, através de uma complexa série de passos, à formação de um produto final resistente chamado A2E. Este composto é completamente resistente à digestão no lisossomo, e assim é uma grande fonte de lixo não degradado nos lisossomos dessas células. Com o tempo, tanto A2E é produzido e absorvido pelos lisossomos sem ser degradado que este pode ocupar até um quinto do volume celular total das células que o acumulam. Estas células desafortunadas produzem o epitélio pigmentar retinal (RPE) dos olhos— uma parte responsável por manter o funcionamento correto das áreas sensíveis à luz na retina.
doenças. A natureza em si do problema é que o corpo simplesmente não tem as enzimas para degradar o lixo realmente pesado, e assim ele irá asfixiar as células, tirar o raciocínio, cegar e entupir artérias mais cedo ou mais tarde
não há acúmulo de lipofuscina em cemitérios— e se houvesse, certamente saberíamos disso, porque a lipofuscina é fluorescente.
a evolução encontraria uma maneira de criar micróbios com a capacidade de digerir qualquer coisa que déssemos a eles que fosse ao mesmo tempo baseada em carbono e rica em energia de forma a ser uma fonte de combustível que valesse a pena. A isso foi dado o inesquecível nome de "princípio da infalibilidade microbiana".
Nosso cérebro está lentamente sendo emaranhado em placas de beta amiloide— a questão é somente em que momento alcançaremos o patamar depois do qual nosso cérebro não conseguirá funcionar suficientemente bem para manter a vida e a identidade que passamos tantos anos construindo. Se não surgir alguma terapia inovadora radical, todos nós seremos afetados pela demência do Alzheimer se alguma outra coisa não nos matar antes.
as células microgliais— as células imunológicas do cérebro— lentamente comem e digerem os depósitos de beta amiloide que ficam nas células nervosas.
Os produtos finais da glicação avançada (ou "AGEs"**, na sigla em inglês, como são adequadamente chamados) são o resultado final dos processos químicos complexos pelos quais a estrutura de proteínas é deformada por causa de açúcares e outros combustíveis.
o básico sobre como os AGEs se formam para entender as diversas estratégias que foram utilizadas na procura de uma forma de nos proteger de sua influência fossilizante. No mecanismo mais bem conhecido (a parte principal da reação de Maillard), uma molécula de açúcar abre sua estrutura e liga- se (processo de "glicação") a uma molécula de proteína, formando uma base de Schiff. Esta estrutura é relativamente instável, de forma que a base de Schiff irá frequentemente se decompor espontaneamente. Algumas vezes, porém, ela se colapsará em uma estrutura mais estável chamada produto de Amadori. Produtos de Amadori têm vida útil muito mais longa do que as bases de Schiff (este fato há muito tem sido utilizado em um teste de laboratório que mede os níveis da hemoglobina glicada ou HbA1c,
um regime de controle intensivo do açúcar no sangue poderia reduzir o risco de diabéticos desenvolverem doenças nos nervos em quase dois terços, doença renal diabética aproximadamente pela metade, e retinopatia diabética em impressionantes três quartos.
a enzima mieloperoxidase, que é usada por macrófagos para matar bactérias ao gerar o tóxico ácido hipocloroso. Foi demonstrado que o ácido hipocloroso, em presença do componente base (para a construção de proteínas) serina, pode induzir a formação de ligações cruzadas do tipo dos AGEs, independentemente da química de combustíveis usual de açúcares e lipídios.
o rejuvenescimento será efetuado assim que pudermos quebrar uma proporção suficiente das estruturas de AGEs em nossos corpos de forma a manter a quantidade total de ligações cruzadas abaixo do patamar a partir do qual de fato seria prejudicado o funcionamento dos tecidos.
O declínio do sistema imunológico é um dos efeitos mais mortais do envelhecimento.
o próprio nome "herpes" é derivado da palavra grega herpein (" rastejar"), em referência a sua capacidade de se esconder no corpo enquanto aguarda condições favoráveis para sua reativação.
interferon gama, um mensageiro químico essencial responsável por aumentar a resposta das células T ao vírus.
a expansão clonal relacionada ao envelhecimento de populações específicas de CD8 reduz a variedade de células T presentes no corpo e compromete a capacidade de implementar uma defesa imunológica efetiva.
Um tratamento para câncer que sugere maneiras de eliminar células T anérgicas é a terapia fotodinâmica (PDT). A PDT começa com um fármaco que, quando iluminado com a luz de um laser, esquenta muito ou produz uma explosão enorme de radicais livres. Existem fármacos que têm esta característica e que são também absorvidos seletivamente por células cancerígenas, o que permite aos oncologistas acumular uma grande quantidade do fármaco fotossensível em células- alvo enquanto evitam em muito a absorção por células normais. Em si, os fármacos de PDT são inofensivos, não tendo efeitos enquanto o paciente não for irradiado com luz.
dendrímeros: minúsculas partículas com estruturas ramificadas requintadamente complexas que se estendem para fora como arbustos, resultando em um formato esférico. Os ramos dos dendrímeros são construídos de uma maneira que nos permite prender uma ampla variedade de moléculas a eles. Isso faz com que sejam como canivetes suíços nanotecnológicos: diversas ferramentas úteis podem estar juntas em um pequeno pacote compacto. Os dendrímeros podem carregar uma molécula para que os direcione a um determinado tipo de célula, um ou mais fármacos mortais ou outros venenos para matar as células- alvo assim que forem localizadas e (caso se deseje) uma molécula que permita aos pesquisadores ou médicos rastrear o progresso do pacote inteiro à medida que se move pelo corpo.
Uma opção que a terapia genética irá nos fornecer é a capacidade de construir um novo mecanismo de suicídio em nossas células T que faria com que se autodestruíssem caso se tornassem anérgicas.
O ganciclovir faz com que os vírus não possam mais usar o maquinário de replicação de DNA de suas células hospedeiras para se reproduzir. Ele faz isso interferindo na atividade da versão incomum do vírus da timidina quinase (TK), uma enzima que é necessária para a síntese de DNA.
o câncer só pode sobreviver se mantiver sua velocidade insana de crescimento, de forma que acabar com isso ao desligar- se sua capacidade de síntese de DNA rapidamente domesticaria os tumores.
toda a resistência à insulina relacionada ao envelhecimento observada, e muito da alteração de sinalização pró- inflamatória relacionada ao envelhecimento, pode atribuir- se ao acúmulo de gordura visceral em excesso, que precede e prevê o desenvolvimento de todos os elementos da síndrome metabólica conhecida como síndrome X: resistência à insulina, colesterol HDL (" bom") baixo e pressão sanguínea, triglicerídeos (lipídios do sangue) e açúcar no sangue altos.
Ao longo de nossas vidas, gradualmente perdemos células vitais para a manutenção contínua da nossa saúde. Muitas doenças fatais do envelhecimento— como o mal de Parkinson— são causadas pela perda de populações de células responsáveis por alguma função crucial no corpo.
As células- tronco embrionárias serão necessárias para desenvolver curas completas para o mal de Parkinson, lesões na medula espinhal, diabetes juvenil, esclerose lateral amiotrófica (" doença de Lou Gehrig"), danos causados por ataques cardíacos, alguns cânceres e outras enfermidades devastadoras— incluindo o próprio envelhecimento.
para o embrião se transformar em um organismo com a estrutura complexa de um ser humano, suas células precisam ter a capacidade de se transformar em cada uma dessas células maduras— uma habilidade chamada pluripotência.
Somente um pequeno número de áreas do cérebro produz células- tronco capazes de se desenvolver para formar novos neurônios: uma subseção do hipocampo chamada zona subgranular do giro dentado, e uma parte da zona subventricular, onde neurônios são criados para suprir o bulbo olfatório (a área do cérebro que processa o sentido do olfato).
Os blastocistos estão em um estágio tão primitivo do desenvolvimento embrionário que ainda não tomaram a "decisão" bioquímica de se tornar um ser humano distinto. Isso é parte da razão pela qual eles ainda têm total flexibilidade para se tornar qualquer tipo de célula do corpo humano— e também da razão pela qual a confusão da tecnologia de células- tronco com o debate sobre o aborto é tão eticamente insensata.
Há diversos métodos propostos para se criar células- tronco embrionárias de blastocistos sem eliminar- se o potencial dessas bolas de células de se tornarem vidas humanas em algum momento. Um é a partenogênese, um nome provindo do termo técnico para um "nascimento virgem". Nesta técnica, os genes em um óvulo (que naturalmente contém somente metade de um conjunto total, já que são conformados para ser completados por aqueles no espermatozoide na fertilização) são duplicados, gerando assim um conjunto completo de instruções de DNA; isto permite que o óvulo se comporte o suficiente como um blastocisto para produzir células- tronco embrionárias para a doadora do óvulo, sem que o óvulo seja de fato fertilizado. Uma outra abordagem é pegar células- tronco de embriões de clínicas de fertilização in vitro que têm defeitos que impedem que cheguem a formar um feto, ou de fato induzir esses defeitos no DNA de um paciente antes de fazer um blastocisto com ele usando a TNCS, de forma a eliminar até mesmo seu potencial de formar uma vida humana. Recentemente, a ACT introduziu mais uma opção: usar células- tronco derivadas de uma única célula tirada do blastocisto, deixando- se o resto delas do jeito que estavam, representando um embrião potencialmente viável (como às vezes já é feito para testes genéticos de embriões de fertilização in vitro antes da implantação). Também há uma quarta opção, que é estimular células- tronco adultas a que se comportem mais como células- tronco embrionárias, usando fatores de crescimento e outros mensageiros químicos, em vez de usar o inerente poder de renovação do óvulo para fazer a mesma coisa.
o impedimento fundamental para o sonho de que novas células reconstituam corpos desgastados pelos anos ou por doenças é político— de forma que sua solução também deve sê- lo.
danos são potencialmente reparáveis, mas se tornam irreparáveis se a célula se dividir antes do reparo ser feito. Essas mudanças permanentes são mutações,
Células individuais adquirem sua função especializada— células cardíacas, hepáticas, renais, da pele— ao desativarem a maior parte de seu DNA, deixando ativos somente aqueles genes que necessitam para realizar sua função específica. Em uma célula típica, somente cerca de um décimo do conjunto completo de genes de uma pessoa está ativo. Portanto, cerca de 90% dos genes em uma célula podem ser danificados de forma irreparável sem afetar- se em nada o funcionamento da célula.
deleções— a remoção completa de grandes faixas de DNA, aniquilando- se muitos genes de uma vez só apesar do evento ser, em termos estritamente técnicos, um único evento de mutação.
metilação— uma alteração química nos genes que os impede de serem expressos.
A única defesa eficaz contra o câncer é proteger a integridade de todos os genes que possuímos.
o que faz do câncer um inimigo tão temível é que é uma doença que está constantemente em evolução, uma colmeia de inventividade genética que continuamente encontra novas e melhores maneiras de superar inteligentemente nossas tentativas de controlá- la.
a lógica de engenharia é ainda mais robusta, porque o mesmo "dano" que poderia chegar a nos matar (neste caso, o esgotamento de nossos telômeros) simultaneamente é a mesma coisa que precisamos assegurar que ocorra, para não sermos mortos de outra forma (a divisão celular descontrolada essencial ao câncer). Colocar uma data de validade em todas as nossas células, mas ao mesmo tempo garantir que haja um reabastecimento regular de novas células, acaba com ambos os problemas de uma vez só.
Um efeito colateral possível da perda da telomerase de todas as nossas células poderia ser a potencial esterilidade dos homens.
A ciência é, em um sentido muito concreto, como a religião: o que um cientista individualmente diz pode ser colocado em dúvida, mas o consenso científico público é sagrado.
Em princípio, a qualidade mais importante em um cientista deveria ser sua capacidade de aceitar, com uma mente aberta, evidências que desafiem as teorias nas quais tenha acreditado por muitos anos.
exequibilidade: a aparente probabilidade de que o cientista completará o programa experimental proposto dentro do prazo e do orçamento pedidos e obterá resultados que merecerão ser publicados em um periódico científico de boa reputação.
se todo mundo tiver um problema de saúde mortal e tivermos a chance de fazer com que ele não seja mais mortal, certamente nos empenharemos em alcançar este objetivo.
Temos as mutações nos nossos cromossomos, é claro, que causam o câncer; a glicação (a alteração da estrutura das proteínas causada pela glicose); e os vários tipos de lixo que se acumulam fora das células (os “agregados extracelulares”: beta amiloides, a menos conhecida transtirretina e possivelmente outras substâncias do mesmo tipo geral).
mutações mitocondriais, que parecem deteriorar a bioquímica celular ao aumentar o estresse oxidativo.
interligados que contribuem para os danos do envelhecimento. Para criar terapias, tudo que seria necessário entender são os danos em si do envelhecimento: as lesões moleculares e celulares que prejudicam a estrutura e o funcionamento dos tecidos do corpo.
vencer o envelhecimento levará à eliminação deste período, ao adiá- lo para idades indefinidamente maiores de forma que as pessoas nunca cheguem a ele.
a vida não é lógica.
o físico Max Planck fez uma observação há mais de oitenta anos em que dizia que "a ciência avança de funeral em funeral", e o biólogo J. B. S. Haldane disse que "há quatro estágios na aceitação: (I) isso é um absurdo inútil; (II) isso é um ponto de vista interessante, mas errado; (III) isso é verdade, mas é pouco importante; (IV) eu sempre disse isso."
as enfermidades do envelhecimento deveriam ser vistas como separadas em dois fenômenos distintos: de um lado, as doenças relacionadas ao envelhecimento, e do outro, "o envelhecimento em si".
envelhecimento é, nem mais nem menos, o conjunto de estágios iniciais das várias doenças relacionadas ao envelhecimento.
acima: a capacidade natural de autorreparo com a qual nascemos é nossa aliada na cruzada contra o envelhecimento, não nossa inimiga.
Quando uma larva de nematódeo segue o caminho dauer, ela pausa seu desenvolvimento por um período que pode durar muito mais do que a vida inteira de um nematódeo que segue o caminho normal não dauer.
O prolongamento de vida como resposta à privação de nutrientes é simplesmente a expressão da intuição geneticamente programada de um organismo em relação ao grau apropriado de atenção aos detalhes que ele deve exercer em seu funcionamento molecular e celular diário— e, por ser essa sua natureza, ele não é passível de melhorias substanciais através de tecnologias biomédicas no futuro próximo.
terapias de reparação repararão uma determinada quantidade de danos, mas não todos os danos, e as terapias de prevenção desacelerarão mas não interromperão o acúmulo de danos.
Os geriatras tentam ajudar as pessoas cujo envelhecimento chegou num ponto em que as funções físicas ou mentais estão consideravelmente prejudicadas.
Os radicais livres são simplesmente reativos demais para serem varridos com vitaminas,
os radicais livres mitocondriais não impulsionam um aumento sistêmico do estresse oxidativo com a idade por danificar diretamente o resto da célula. Em vez disso, o dano que eles causam ao DNA mitocondrial faz com que a mitocôndria entre em um estado mal- adaptativo que espalha o estresse oxidativo mais além da célula.
Na biologia, radicais livres são, em geral, moléculas à base de oxigênio que perderam um de seus elétrons em relação a sua quantidade normal.
o fato é que a esmagadora maioria dos radicais livres aos quais o corpo é exposto é gerada nas próprias células humanas— nas mitocôndrias, nossas "usinas de energia" celulares.
as mitocôndrias criam resíduos tóxicos durante a conversão de energia de uma forma para outra.
A restrição calórica— a única intervenção não genética que sabidamente diminui a velocidade do envelhecimento em mamíferos— melhora todos esses parâmetros: ela diminui a geração de radicais livres mitocondriais, fortalece as membranas mitocondriais contra o ataque dos radicais livres, e acima de tudo reduz o acúmulo de mutações no DNA mitocondrial relacionado ao envelhecimento (a remoção ou reescrita irreparável de "letras" do livro de instruções genético).
Tanto em pessoas de cinco quanto de cinquenta anos de idade, qualquer mitocôndria em suas células possui membranas e proteínas que têm em média somente algumas semanas de idade. Assim, os componentes mitocondriais mais novos e mais velhos estão presentes na mesma proporção tanto nas pessoas mais velhas quanto nas mais novas. Simplesmente não é possível que o envelhecimento seja impulsionado por um processo progressivo de degeneração de componentes que na realidade sofrem um processo contínuo de renovação.
O envelhecimento é uma doença pandêmica mortal,
A catalase quebra o peróxido de hidrogênio— uma molécula similar aos radicais livres— transformando- o na inofensiva água antes de que possa se tornar mais perigoso e causar sérios danos moleculares.
a desregulação crônica dos caminhos de sinalização das células seria um alto preço a pagar por um menor estresse oxidativo.
"idiomas" do DNA das mitocôndrias e do núcleo da célula desenvolveram "dialetos" ligeiramente diferentes, de forma que uma cópia exata de uma determinada sequência de DNA mitocondrial torna- se indecifrável quando é colocada no núcleo. Este problema chama- se disparidade de código.
gene mitocondrial chamado ND4; as mutações neste gene causam uma mitocondriopatia— a neuropatia óptica hereditária de Leber (LHON).
Inteínas são sequências que são inseridas temporariamente em algumas proteínas logo que são sintetizadas, possivelmente para ajudar a proteína a amadurecer adequadamente até sua forma final, e então são removidas após cumprirem seu propósito.
capacidade de introduzir na mitocôndria versões modificadas, não de genes individuais (como na abordagem clássica da terapia genética), mas de cópias completas do DNA mitocondrial inteiro. Eles conseguiram realizar esse procedimento— que denominaram protofecção
trabalho do lisossomo não é destruir completamente os resíduos celulares, mas decompô- los a nível molecular em componentes mais básicos que podem ser usados como matéria- prima para a biossíntese de novas membranas celulares, enzimas e outros componentes importantes do maquinário celular.
teoria do envelhecimento por "catástrofe de lixo", na qual a lipofuscina que vai se acumulando dentro do lisossomo dilui a acidez da organela e o suprimento de enzimas.
Os pesquisadores tendem a se refugiar em seus campos de estudo estreitamente especializados, e consequentemente eles também raramente trocam informações e observam a confluência de observações em diferentes campos da ciência (ou mesmo em subcampos dentro destes campos).
o trans- retinal pode reagir com algumas moléculas lipídicas que formam a membrana celular, levando, através de uma complexa série de passos, à formação de um produto final resistente chamado A2E. Este composto é completamente resistente à digestão no lisossomo, e assim é uma grande fonte de lixo não degradado nos lisossomos dessas células. Com o tempo, tanto A2E é produzido e absorvido pelos lisossomos sem ser degradado que este pode ocupar até um quinto do volume celular total das células que o acumulam. Estas células desafortunadas produzem o epitélio pigmentar retinal (RPE) dos olhos— uma parte responsável por manter o funcionamento correto das áreas sensíveis à luz na retina.
doenças. A natureza em si do problema é que o corpo simplesmente não tem as enzimas para degradar o lixo realmente pesado, e assim ele irá asfixiar as células, tirar o raciocínio, cegar e entupir artérias mais cedo ou mais tarde
não há acúmulo de lipofuscina em cemitérios— e se houvesse, certamente saberíamos disso, porque a lipofuscina é fluorescente.
a evolução encontraria uma maneira de criar micróbios com a capacidade de digerir qualquer coisa que déssemos a eles que fosse ao mesmo tempo baseada em carbono e rica em energia de forma a ser uma fonte de combustível que valesse a pena. A isso foi dado o inesquecível nome de "princípio da infalibilidade microbiana".
Nosso cérebro está lentamente sendo emaranhado em placas de beta amiloide— a questão é somente em que momento alcançaremos o patamar depois do qual nosso cérebro não conseguirá funcionar suficientemente bem para manter a vida e a identidade que passamos tantos anos construindo. Se não surgir alguma terapia inovadora radical, todos nós seremos afetados pela demência do Alzheimer se alguma outra coisa não nos matar antes.
as células microgliais— as células imunológicas do cérebro— lentamente comem e digerem os depósitos de beta amiloide que ficam nas células nervosas.
Os produtos finais da glicação avançada (ou "AGEs"**, na sigla em inglês, como são adequadamente chamados) são o resultado final dos processos químicos complexos pelos quais a estrutura de proteínas é deformada por causa de açúcares e outros combustíveis.
o básico sobre como os AGEs se formam para entender as diversas estratégias que foram utilizadas na procura de uma forma de nos proteger de sua influência fossilizante. No mecanismo mais bem conhecido (a parte principal da reação de Maillard), uma molécula de açúcar abre sua estrutura e liga- se (processo de "glicação") a uma molécula de proteína, formando uma base de Schiff. Esta estrutura é relativamente instável, de forma que a base de Schiff irá frequentemente se decompor espontaneamente. Algumas vezes, porém, ela se colapsará em uma estrutura mais estável chamada produto de Amadori. Produtos de Amadori têm vida útil muito mais longa do que as bases de Schiff (este fato há muito tem sido utilizado em um teste de laboratório que mede os níveis da hemoglobina glicada ou HbA1c,
um regime de controle intensivo do açúcar no sangue poderia reduzir o risco de diabéticos desenvolverem doenças nos nervos em quase dois terços, doença renal diabética aproximadamente pela metade, e retinopatia diabética em impressionantes três quartos.
a enzima mieloperoxidase, que é usada por macrófagos para matar bactérias ao gerar o tóxico ácido hipocloroso. Foi demonstrado que o ácido hipocloroso, em presença do componente base (para a construção de proteínas) serina, pode induzir a formação de ligações cruzadas do tipo dos AGEs, independentemente da química de combustíveis usual de açúcares e lipídios.
o rejuvenescimento será efetuado assim que pudermos quebrar uma proporção suficiente das estruturas de AGEs em nossos corpos de forma a manter a quantidade total de ligações cruzadas abaixo do patamar a partir do qual de fato seria prejudicado o funcionamento dos tecidos.
O declínio do sistema imunológico é um dos efeitos mais mortais do envelhecimento.
o próprio nome "herpes" é derivado da palavra grega herpein (" rastejar"), em referência a sua capacidade de se esconder no corpo enquanto aguarda condições favoráveis para sua reativação.
interferon gama, um mensageiro químico essencial responsável por aumentar a resposta das células T ao vírus.
a expansão clonal relacionada ao envelhecimento de populações específicas de CD8 reduz a variedade de células T presentes no corpo e compromete a capacidade de implementar uma defesa imunológica efetiva.
Um tratamento para câncer que sugere maneiras de eliminar células T anérgicas é a terapia fotodinâmica (PDT). A PDT começa com um fármaco que, quando iluminado com a luz de um laser, esquenta muito ou produz uma explosão enorme de radicais livres. Existem fármacos que têm esta característica e que são também absorvidos seletivamente por células cancerígenas, o que permite aos oncologistas acumular uma grande quantidade do fármaco fotossensível em células- alvo enquanto evitam em muito a absorção por células normais. Em si, os fármacos de PDT são inofensivos, não tendo efeitos enquanto o paciente não for irradiado com luz.
dendrímeros: minúsculas partículas com estruturas ramificadas requintadamente complexas que se estendem para fora como arbustos, resultando em um formato esférico. Os ramos dos dendrímeros são construídos de uma maneira que nos permite prender uma ampla variedade de moléculas a eles. Isso faz com que sejam como canivetes suíços nanotecnológicos: diversas ferramentas úteis podem estar juntas em um pequeno pacote compacto. Os dendrímeros podem carregar uma molécula para que os direcione a um determinado tipo de célula, um ou mais fármacos mortais ou outros venenos para matar as células- alvo assim que forem localizadas e (caso se deseje) uma molécula que permita aos pesquisadores ou médicos rastrear o progresso do pacote inteiro à medida que se move pelo corpo.
Uma opção que a terapia genética irá nos fornecer é a capacidade de construir um novo mecanismo de suicídio em nossas células T que faria com que se autodestruíssem caso se tornassem anérgicas.
O ganciclovir faz com que os vírus não possam mais usar o maquinário de replicação de DNA de suas células hospedeiras para se reproduzir. Ele faz isso interferindo na atividade da versão incomum do vírus da timidina quinase (TK), uma enzima que é necessária para a síntese de DNA.
o câncer só pode sobreviver se mantiver sua velocidade insana de crescimento, de forma que acabar com isso ao desligar- se sua capacidade de síntese de DNA rapidamente domesticaria os tumores.
toda a resistência à insulina relacionada ao envelhecimento observada, e muito da alteração de sinalização pró- inflamatória relacionada ao envelhecimento, pode atribuir- se ao acúmulo de gordura visceral em excesso, que precede e prevê o desenvolvimento de todos os elementos da síndrome metabólica conhecida como síndrome X: resistência à insulina, colesterol HDL (" bom") baixo e pressão sanguínea, triglicerídeos (lipídios do sangue) e açúcar no sangue altos.
Ao longo de nossas vidas, gradualmente perdemos células vitais para a manutenção contínua da nossa saúde. Muitas doenças fatais do envelhecimento— como o mal de Parkinson— são causadas pela perda de populações de células responsáveis por alguma função crucial no corpo.
As células- tronco embrionárias serão necessárias para desenvolver curas completas para o mal de Parkinson, lesões na medula espinhal, diabetes juvenil, esclerose lateral amiotrófica (" doença de Lou Gehrig"), danos causados por ataques cardíacos, alguns cânceres e outras enfermidades devastadoras— incluindo o próprio envelhecimento.
para o embrião se transformar em um organismo com a estrutura complexa de um ser humano, suas células precisam ter a capacidade de se transformar em cada uma dessas células maduras— uma habilidade chamada pluripotência.
Somente um pequeno número de áreas do cérebro produz células- tronco capazes de se desenvolver para formar novos neurônios: uma subseção do hipocampo chamada zona subgranular do giro dentado, e uma parte da zona subventricular, onde neurônios são criados para suprir o bulbo olfatório (a área do cérebro que processa o sentido do olfato).
Os blastocistos estão em um estágio tão primitivo do desenvolvimento embrionário que ainda não tomaram a "decisão" bioquímica de se tornar um ser humano distinto. Isso é parte da razão pela qual eles ainda têm total flexibilidade para se tornar qualquer tipo de célula do corpo humano— e também da razão pela qual a confusão da tecnologia de células- tronco com o debate sobre o aborto é tão eticamente insensata.
Há diversos métodos propostos para se criar células- tronco embrionárias de blastocistos sem eliminar- se o potencial dessas bolas de células de se tornarem vidas humanas em algum momento. Um é a partenogênese, um nome provindo do termo técnico para um "nascimento virgem". Nesta técnica, os genes em um óvulo (que naturalmente contém somente metade de um conjunto total, já que são conformados para ser completados por aqueles no espermatozoide na fertilização) são duplicados, gerando assim um conjunto completo de instruções de DNA; isto permite que o óvulo se comporte o suficiente como um blastocisto para produzir células- tronco embrionárias para a doadora do óvulo, sem que o óvulo seja de fato fertilizado. Uma outra abordagem é pegar células- tronco de embriões de clínicas de fertilização in vitro que têm defeitos que impedem que cheguem a formar um feto, ou de fato induzir esses defeitos no DNA de um paciente antes de fazer um blastocisto com ele usando a TNCS, de forma a eliminar até mesmo seu potencial de formar uma vida humana. Recentemente, a ACT introduziu mais uma opção: usar células- tronco derivadas de uma única célula tirada do blastocisto, deixando- se o resto delas do jeito que estavam, representando um embrião potencialmente viável (como às vezes já é feito para testes genéticos de embriões de fertilização in vitro antes da implantação). Também há uma quarta opção, que é estimular células- tronco adultas a que se comportem mais como células- tronco embrionárias, usando fatores de crescimento e outros mensageiros químicos, em vez de usar o inerente poder de renovação do óvulo para fazer a mesma coisa.
o impedimento fundamental para o sonho de que novas células reconstituam corpos desgastados pelos anos ou por doenças é político— de forma que sua solução também deve sê- lo.
danos são potencialmente reparáveis, mas se tornam irreparáveis se a célula se dividir antes do reparo ser feito. Essas mudanças permanentes são mutações,
Células individuais adquirem sua função especializada— células cardíacas, hepáticas, renais, da pele— ao desativarem a maior parte de seu DNA, deixando ativos somente aqueles genes que necessitam para realizar sua função específica. Em uma célula típica, somente cerca de um décimo do conjunto completo de genes de uma pessoa está ativo. Portanto, cerca de 90% dos genes em uma célula podem ser danificados de forma irreparável sem afetar- se em nada o funcionamento da célula.
deleções— a remoção completa de grandes faixas de DNA, aniquilando- se muitos genes de uma vez só apesar do evento ser, em termos estritamente técnicos, um único evento de mutação.
metilação— uma alteração química nos genes que os impede de serem expressos.
A única defesa eficaz contra o câncer é proteger a integridade de todos os genes que possuímos.
o que faz do câncer um inimigo tão temível é que é uma doença que está constantemente em evolução, uma colmeia de inventividade genética que continuamente encontra novas e melhores maneiras de superar inteligentemente nossas tentativas de controlá- la.
a lógica de engenharia é ainda mais robusta, porque o mesmo "dano" que poderia chegar a nos matar (neste caso, o esgotamento de nossos telômeros) simultaneamente é a mesma coisa que precisamos assegurar que ocorra, para não sermos mortos de outra forma (a divisão celular descontrolada essencial ao câncer). Colocar uma data de validade em todas as nossas células, mas ao mesmo tempo garantir que haja um reabastecimento regular de novas células, acaba com ambos os problemas de uma vez só.
Um efeito colateral possível da perda da telomerase de todas as nossas células poderia ser a potencial esterilidade dos homens.
A ciência é, em um sentido muito concreto, como a religião: o que um cientista individualmente diz pode ser colocado em dúvida, mas o consenso científico público é sagrado.
Em princípio, a qualidade mais importante em um cientista deveria ser sua capacidade de aceitar, com uma mente aberta, evidências que desafiem as teorias nas quais tenha acreditado por muitos anos.
exequibilidade: a aparente probabilidade de que o cientista completará o programa experimental proposto dentro do prazo e do orçamento pedidos e obterá resultados que merecerão ser publicados em um periódico científico de boa reputação.
se todo mundo tiver um problema de saúde mortal e tivermos a chance de fazer com que ele não seja mais mortal, certamente nos empenharemos em alcançar este objetivo.
June 19, 2023
I could tell that this book was "old" in the sense of barely any mention of anything that even resembles CRISPR. The world has really changed a lot in the 15+ years since its publishing. The reason why this doesn't get the full five stars is because it's simply too advanced. I've read a lot from Sapolsky, entire book(s) on CRISPR, discovery of DNA, also listened to that Immune book and also one about Dopamine, and a bunch more, and never had any problems understanding and digging deep into a particular medical topic. The book tries to remain accessible to the layperson but fails at that. The text is so serious and dense that I couldn't recite or name a single thing.
What did I take away? That if all goes well, I'll probably not die of natural causes. It has a highly optimistic undertone, that we'll live to be 1000 (unless you are already 80, then you are doomed). And I can't wait where the anti-aging stuff takes us in the next few decades. But, and that's a big but(t), damn political and ethical constraints will probably hinder most of the good developments, along with genetic engineering, leading to a delayed materialization of these innovations. Probably to a point where it's too late for the current generation. Even then, you'll probably need a good $250K spare cash laying around to get meaningfully treated, so that's how I aim to live [to have that]. It'd be a pity having the tech to live longer, especially not as a raisin but relatively young-looking and not be able to afford that. Let's be honest, it won't be cheap else everyone could have it then we'd overpopulate Earth even more.
Those would rate it 5 probably understand it better and likely have a medical background to know what's up. I'm looking forward to more recent and more dumbed-down popscience books that I could better enjoy, but otherwise this was decent enough to get my interest going. But allow me to be the witch in pink heels saying just point me to the nearest anti-aging clinic, mkay? I mean until that comes, wth can I even do? The book mentions donating to the cause or asking your political representative to allow stemcell experiments on fertility clinics' discarded embryos or whatever. Well, in my country our representatives are busy fighting each other, migrants, and the price of chicken breast. Even if the tech is on the way, society's stupidity drag will postpone the good stuff probably way too long. Same with designer babies, the unavailability of which is a factor in why am I childfree (if I can't influence my offspring's looks and genetic makeup I'd rather not have one, thanks). Until big pharma picks these up we can't even realistically invest in promising tech.
What did I take away? That if all goes well, I'll probably not die of natural causes. It has a highly optimistic undertone, that we'll live to be 1000 (unless you are already 80, then you are doomed). And I can't wait where the anti-aging stuff takes us in the next few decades. But, and that's a big but(t), damn political and ethical constraints will probably hinder most of the good developments, along with genetic engineering, leading to a delayed materialization of these innovations. Probably to a point where it's too late for the current generation. Even then, you'll probably need a good $250K spare cash laying around to get meaningfully treated, so that's how I aim to live [to have that]. It'd be a pity having the tech to live longer, especially not as a raisin but relatively young-looking and not be able to afford that. Let's be honest, it won't be cheap else everyone could have it then we'd overpopulate Earth even more.
Those would rate it 5 probably understand it better and likely have a medical background to know what's up. I'm looking forward to more recent and more dumbed-down popscience books that I could better enjoy, but otherwise this was decent enough to get my interest going. But allow me to be the witch in pink heels saying just point me to the nearest anti-aging clinic, mkay? I mean until that comes, wth can I even do? The book mentions donating to the cause or asking your political representative to allow stemcell experiments on fertility clinics' discarded embryos or whatever. Well, in my country our representatives are busy fighting each other, migrants, and the price of chicken breast. Even if the tech is on the way, society's stupidity drag will postpone the good stuff probably way too long. Same with designer babies, the unavailability of which is a factor in why am I childfree (if I can't influence my offspring's looks and genetic makeup I'd rather not have one, thanks). Until big pharma picks these up we can't even realistically invest in promising tech.
Read
February 16, 2022kindling the sparks that we must fan into a blaze that will cast out its obscuring darkness and melt its frozen grip."
maybe I should have—but there's a trade-off
I've been spending every waking hour
There are mutations in our chromosomes, of course, which cause cancer. There is glycation, the warping of proteins by glucose. There are the various kinds of junk that accumulate outside the cell ("extracellular aggregates"): beta-amyloid, the lesser-known transthyretin, and possibly other substances of the same general sort. There is also the unwholesome goo that builds up within the cell ("intracellular aggregates"), such as lipofuscin. There's cellular senescence, the "aging" of individual cells, which puts them into a state of arrested growth and causes them to produce chemical signals dangerous to their neighbors. And there's the depletion of the stem cell pools essential to healing and maintenance of tissue. And of course, there are mitochondrial mutations, which seem to disrupt cellular biochemistry by increasing oxidative stress. I had for a few years felt optimistic that scientists could solve this problem by copying mitochondrial DNA from its vulnerable spot at "ground zero," within the free-radical generating mitochondria, into the bomb shelter of the cell nucleus, where damage to DNA is vastly rarer.
Grabbing a notepad, I jotted down the molecular and cellular changes that I could confidently list as important targets for the new class of antiaging therapies that I would soon call SENS, the "Strategies for Engineered Negligible Senescence."
regard all lives equally. For example, saving an eighty-year-old from drowning may give him only a few extra years of life before he's likely to die of something else, whereas saving a child from drowning gives him a probable seventy years or more of extra life. We may also take into account the quality of life of the persons whose lives we save
So here's my modified question: How many healthy, youthful years in total do you think you could add to people's lives, in your life?
donating money or time to the Methuselah Foundation's Mprize fund or its SENS research funding program
Around 150,000 people die each day worldwide—that's nearly two per second—and of those, about two-thirds die of aging. That's right: 100,000 people. That's about thirty World Trade Centers, sixty Katrinas, every single day.
Many people, when thinking about the idea of adding years to life, commit the "Tithonus error"—the presumption that, when we talk about combating aging, we're only talking about stretching out the grim years of debilitation and disease
In fact, the opposite is true: the defeat of aging will entail the elimination of that period, by postponing it to indefinitely greater ages so that people never reach it.
the average person in the industrialized world consumes more health-care resources in his or her last year of life than in an entire life up to that point, irrespective of age at death, so we're talking about trillions of dollars per year.
Until recently, no one has had any coherent idea how to defeat aging, it makes perfect psychological sense to put it out of one's mind—to make one's peace with it
J. B. S. Haldane noted that "there are four stages of acceptance: (i) this is worthless nonsense; (ii) this is an interesting, but perverse point of view; (iii) this is true, but quite unimportant; (iv) I always said so."
improvements in that technology, allow us to stop people dying of aging at any age— equivalent to the effect of today's antiretrovirals against HIV
This is a milestone that I've termed "robust mouse rejuvenation," or RMR
Aging has held us in a psychological stranglehold ever since we realized it existed, and that stranglehold remains intact to this day.
non-zero, but high enough to justify my having broken your pro-aging trance
gerontologists hoped to ringfence it
most types are never seen in people below the age of forty or so (except for people with very rare congenital DNA repair deficiencies)
There is no ticking time bomb—just the accumulation of damage.
biogerontologists, the people who study aging
He realized that it might be possible to breed longer lived organisms, rather in the vein of the Howard families in Robert Heinlein's Lazarus Long books, by maintaining them over many generations and only allowing those with the longest lives (actually, strictly speaking the longest reproductive lives) to contribute to the next generation. It would take many more generations than Heinlein described, but Rose was working with fruit flies, which reach maturity only a week after their own conception. And it worked, spectacularly: Rose was eventually able to achieve average lifespans twice those in his starting population.
single genes can be modified in the test tube and then introduced into the body by gene therapy: either germline gene therapy, which affects only the recipient's descendents, or somatic gene therapy, which affects the organism that receives the treatment.
there are many circumstances in which a quick and dirty job is the best policy, because the advantages of the "quick" outweigh the disadvantages of the "dirty." There are certainly other circumstances in which the balance is reversed
The only species in which aging is actively driven by genetic machinery are those (such as salmon) in which there is some reason to age and die rapidly
when you compare different species that are same size, the one that matures later tends to be the longer-lived.
Thus, famine shifts the happy medium toward favoring a more
whether by calorie restriction (CR) itself, or by drugs that trick the body into thinking it's being starved, or by genetic changes that flip the same switch
mitochondrial gene therapy proposal might (and I emphasize might) also slow the rate of aging in humans attributable to most other causes by about 50 percent
negating the effect of the intervention by eliciting a counterbalancing metabolic adjustment. For example, chronic inflammation is a source of cellular damage. But if you interfere with inflammation, you might impair immune defenses against pathogens. Equally, free radicals—a by-product of your metabolism—cause oxidative stress and damage over time. But crank up antioxidants, to defend against free radicals, and you might help cancer cells to protect themselves against chemotherapy drugs.
maybe I should have—but there's a trade-off
I've been spending every waking hour
There are mutations in our chromosomes, of course, which cause cancer. There is glycation, the warping of proteins by glucose. There are the various kinds of junk that accumulate outside the cell ("extracellular aggregates"): beta-amyloid, the lesser-known transthyretin, and possibly other substances of the same general sort. There is also the unwholesome goo that builds up within the cell ("intracellular aggregates"), such as lipofuscin. There's cellular senescence, the "aging" of individual cells, which puts them into a state of arrested growth and causes them to produce chemical signals dangerous to their neighbors. And there's the depletion of the stem cell pools essential to healing and maintenance of tissue. And of course, there are mitochondrial mutations, which seem to disrupt cellular biochemistry by increasing oxidative stress. I had for a few years felt optimistic that scientists could solve this problem by copying mitochondrial DNA from its vulnerable spot at "ground zero," within the free-radical generating mitochondria, into the bomb shelter of the cell nucleus, where damage to DNA is vastly rarer.
Grabbing a notepad, I jotted down the molecular and cellular changes that I could confidently list as important targets for the new class of antiaging therapies that I would soon call SENS, the "Strategies for Engineered Negligible Senescence."
regard all lives equally. For example, saving an eighty-year-old from drowning may give him only a few extra years of life before he's likely to die of something else, whereas saving a child from drowning gives him a probable seventy years or more of extra life. We may also take into account the quality of life of the persons whose lives we save
So here's my modified question: How many healthy, youthful years in total do you think you could add to people's lives, in your life?
donating money or time to the Methuselah Foundation's Mprize fund or its SENS research funding program
Around 150,000 people die each day worldwide—that's nearly two per second—and of those, about two-thirds die of aging. That's right: 100,000 people. That's about thirty World Trade Centers, sixty Katrinas, every single day.
Many people, when thinking about the idea of adding years to life, commit the "Tithonus error"—the presumption that, when we talk about combating aging, we're only talking about stretching out the grim years of debilitation and disease
In fact, the opposite is true: the defeat of aging will entail the elimination of that period, by postponing it to indefinitely greater ages so that people never reach it.
the average person in the industrialized world consumes more health-care resources in his or her last year of life than in an entire life up to that point, irrespective of age at death, so we're talking about trillions of dollars per year.
Until recently, no one has had any coherent idea how to defeat aging, it makes perfect psychological sense to put it out of one's mind—to make one's peace with it
J. B. S. Haldane noted that "there are four stages of acceptance: (i) this is worthless nonsense; (ii) this is an interesting, but perverse point of view; (iii) this is true, but quite unimportant; (iv) I always said so."
improvements in that technology, allow us to stop people dying of aging at any age— equivalent to the effect of today's antiretrovirals against HIV
This is a milestone that I've termed "robust mouse rejuvenation," or RMR
Aging has held us in a psychological stranglehold ever since we realized it existed, and that stranglehold remains intact to this day.
non-zero, but high enough to justify my having broken your pro-aging trance
gerontologists hoped to ringfence it
most types are never seen in people below the age of forty or so (except for people with very rare congenital DNA repair deficiencies)
There is no ticking time bomb—just the accumulation of damage.
biogerontologists, the people who study aging
He realized that it might be possible to breed longer lived organisms, rather in the vein of the Howard families in Robert Heinlein's Lazarus Long books, by maintaining them over many generations and only allowing those with the longest lives (actually, strictly speaking the longest reproductive lives) to contribute to the next generation. It would take many more generations than Heinlein described, but Rose was working with fruit flies, which reach maturity only a week after their own conception. And it worked, spectacularly: Rose was eventually able to achieve average lifespans twice those in his starting population.
single genes can be modified in the test tube and then introduced into the body by gene therapy: either germline gene therapy, which affects only the recipient's descendents, or somatic gene therapy, which affects the organism that receives the treatment.
there are many circumstances in which a quick and dirty job is the best policy, because the advantages of the "quick" outweigh the disadvantages of the "dirty." There are certainly other circumstances in which the balance is reversed
The only species in which aging is actively driven by genetic machinery are those (such as salmon) in which there is some reason to age and die rapidly
when you compare different species that are same size, the one that matures later tends to be the longer-lived.
Thus, famine shifts the happy medium toward favoring a more
whether by calorie restriction (CR) itself, or by drugs that trick the body into thinking it's being starved, or by genetic changes that flip the same switch
mitochondrial gene therapy proposal might (and I emphasize might) also slow the rate of aging in humans attributable to most other causes by about 50 percent
negating the effect of the intervention by eliciting a counterbalancing metabolic adjustment. For example, chronic inflammation is a source of cellular damage. But if you interfere with inflammation, you might impair immune defenses against pathogens. Equally, free radicals—a by-product of your metabolism—cause oxidative stress and damage over time. But crank up antioxidants, to defend against free radicals, and you might help cancer cells to protect themselves against chemotherapy drugs.
March 25, 2008
My gut feeling is this book is overly optimistic about how easily aging will be overcome in the near future, but as Ray Kurzweil would say human intuition is really bad when it comes to scientific/technological progress. The premise sounds good: don’t try to fix the all the complex metabolic pathways that contribute to aging, that’s near impossible, instead just try to clean up all the toxins and junk that builds up with age, and we will stay youthful. Of course it’s a little more complex than that since de Grey’s plan includes moving mitochondrial DNA to the nucleus and completely removing the gene the encodes for telomerase to stop cancer in its tracks.
My only real complaint about the book is that de Grey does a terrible job convincing the reader that living forever is desirable and that the world could even cope. Out of context from a Ray Kurzweil future this book must seem absolutely mad. The writing itself is also a bit inconsistent, since the first part explaining why anyone would want to live forever is near incoherent and many of the technical parts have lots of lame forced analogies. Then there are mini rants, like one against US stem cell research policies which was a bit out of place since the book is mostly technical, although these rants were usually the best written parts.
Overall I was convinced there is a clear cut path for medical science to pursue to end aging, but I’m not sure I’d recommend this book to anyone who doesn’t at least think there is a remote possibility that the singularity is near.
Check http://www.mprize.org/ to see the progress on ending aging.
My only real complaint about the book is that de Grey does a terrible job convincing the reader that living forever is desirable and that the world could even cope. Out of context from a Ray Kurzweil future this book must seem absolutely mad. The writing itself is also a bit inconsistent, since the first part explaining why anyone would want to live forever is near incoherent and many of the technical parts have lots of lame forced analogies. Then there are mini rants, like one against US stem cell research policies which was a bit out of place since the book is mostly technical, although these rants were usually the best written parts.
Overall I was convinced there is a clear cut path for medical science to pursue to end aging, but I’m not sure I’d recommend this book to anyone who doesn’t at least think there is a remote possibility that the singularity is near.
Check http://www.mprize.org/ to see the progress on ending aging.
November 6, 2023
'Ending Aging' presents a groundbreaking exploration of the possibilities and strategies for combating and reversing the ageing process.
The majority of scientists studying ageing biology believe that we will eventually be able to significantly slow down the ageing process, allowing us to live longer and more youthful lives. Dr. Aubrey de Grey is particularly optimistic about this possibility. Dr. de Grey envisions a biomedical technology that can not only slow down ageing-related decline but also reverse it periodically, keeping us biologically young for an extended and indefinite period of time.
In this review, we will take a closer look at Dr. de Grey’s perspective of ageing which he presents in his book ‘Ending Aging.’
About the authors
Aubrey de Grey, Ph.D., is a prominent figure in the field of gerontology and a leading advocate for the development of interventions to reverse the ageing process.
He is a chairman and chief science officer of the Methuselah Foundation, an organisation dedicated to advancing rejuvenation biotechnology. One of De Grey’s notable contributions is the formulation of a comprehensive plan called SENS (Strategies for Engineered Negligible Senescence). This plan aims to indefinitely postpone age-related physical and mental decline by addressing the underlying causes of ageing.
Michael Rae is Dr. de Grey’s research assistant. He has authored numerous scientific articles and commentaries published in respected peer-reviewed journals. Rae has a strong affiliation with the Calorie Restriction Society, where he has been a member for an extended period and previously served on the board. He has made significant contributions to society’s ‘How-to Guide’ and is a core scientific investigator involved in the Cohort Study. This study aims to investigate the feasibility of calorie restriction in humans and explore the potential anti-ageing effects observed in laboratory organisms.
What is the book about?
In ‘Ending Aging,’ Aubrey de Gray aims to shift the public perception of ageing from an inevitable part of life to a treatable disease. De Gray outlines seven primary causes of ageing and delves into the complexities of addressing them. His proposed approach lies between traditional gerontology (treating ageing-related diseases after their onset) and geriatrics (preventing diseases before they occur). Instead, he advocates for intervening just before accumulated damage transforms into a disease, aiming to cure the damage at that critical point.
The author highlights that the root cause of ageing is the gradual accumulation of damage within cells over time. The mitochondria, responsible for converting food into energy, are particularly susceptible to damage due to the constant supply of oxygen. Although cells have mechanisms to repair this damage, they eventually become overwhelmed, leading to ageing-related diseases.
Among the seven causes of ageing, the book touches on issues like glycation, lipofuscin, and AGE cross-links, all contributing to damage accumulation within and outside cells. The author compares the body to a car that can be continuously repaired over time, proposing that middle-aged individuals would be suitable candidates for these repair therapies.
De Gray discusses various potential methodologies for these repair therapies, including stem cells, gene therapies, drugs, and the significance of mouse rejuvenation experiments. He also emphasises the importance of maintaining good health through exercise and diet to live long enough to benefit from these therapies.
Key takeaways from ‘Ending Aging’
1. A cure for ageing lies in repair
While traditional medicine often focuses on symptom management through medication, it fails to tackle the underlying problems. Preventive measures are also limited when it comes to ageing due to the complex nature of the process.
Instead, the book proposes a different approach: repairing the accumulated damage caused by ageing. By starting the treatment of ageing at a certain point in life, such as 40 years old, and addressing the damage up to that point, one can potentially reset the biological age to a younger state. Continuously repairing and maintaining the body’s condition can then extend lifespan significantly.
Using this approach, a person who would have had a life expectancy of 80 years could potentially live up to 120 or even 160 years.
2. Mutations in mitochondria are a major factor in ageing
Free radicals, unstable atoms with unpaired electrons, are highly reactive and can cause damage to molecules within the body.
The mutations caused by free radicals in mitochondrial DNA contribute to accelerated ageing. To address this issue, the book suggests allotopic expression as a solution. Allotopic expression involves safeguarding a healthy backup copy of mitochondrial DNA in the nucleus of each cell. By doing so, the DNA is protected from exposure to free radicals, potentially preventing age-related damage.
3.The first step to winning the war against ageing is to change our mindset
The key takeaway from this book is the urgent need to shift our mindset and approach to anti-ageing treatments. While many promising interventions are still in the experimental stages, waiting for extensive funding and drug trials to be approved comes at a high cost. Aubrey de Grey argues that the time wasted in this process actually leads to more lives lost than the risks associated with experimental treatments.
The book highlights that for every person who may pass away due to an experimental drug, there are ten others who lose their lives because they had to wait too long for approved treatments.
The key message is that embracing some level of risk and accepting that not every treatment will succeed is crucial for advancing anti-ageing research. By overcoming the fear of failure and acknowledging that there may be casualties along the way, we can avoid unnecessary delays and propel the development of life-extending therapies, ultimately bringing us closer to a future without the limitations of ageing.
Strengths and weaknesses, according to readers’ reviews
Strengths:
• Provides a comprehensive overview of various forms of ageing and strategies to address them, making it a valuable primer in biology for readers without a strong background in the subject.
• Despite being published in 2007, the book still imparts significant knowledge, especially in the realm of biology, and helps readers catch up with current issues and developments in the field.
• The writing style is engaging and informative, with delightful analogies that aid in understanding complex biology concepts.
Weaknesses:
• The book is highly theoretical and delves into advanced biology, making it difficult for laypersons to understand, particularly in the second part where deep dives into scientific concepts are presented.
Best quotes from ‘Ending Aging’
“I have been aware for many years that most people do not think about aging in the same way that they think about cancer, or diabetes, or heart disease. They are strongly in favor of the absolute elimination of such diseases as soon as possible, but the idea of eliminating aging – maintaining truly youthful physical and mental function indefinitely – evokes an avalanche of fears and reservations. Yet, in the sense that matters most, aging is just like smoking: It’s really bad for you.”
“Science is about the testing and refinement of hypotheses and theories. In principle, the most important quality of a scientist should be their ability to accept, with an open mind, evidence that challenges theories that they had believed for many years. But scientists are human, and moreover they know that the scientists that produced the new evidence are also human. In particular, they know that when a result is reported that contradicts established conventional thinking, the new evidence is often found later on to have been the result of experimental error.”
“Every day of your life, the same processes that are involved in the browning of meats and other glazed or fried foods are insidiously at work in your body. In your arteries. In your kidneys. In your heart, your eyes, your skin, your nerves. At this very moment, in all your tissues, the sugar that provides your body with so much of its energy is also performing some unwanted chemical experiments, caramelizing your body through exactly the same processes that caramelize onions or peanut brittle. Slowly but steadily, unwanted bonding by sugars and fats handcuffs your proteins, inactivates your enzymes, triggers unhealthy chemical signals in your cells, and damages your DNA. Aging you.”
Final takeaway
‘Ending Aging’ by Aubrey de Grey offers a compelling perspective on slowing down and reversing the ageing process. The book provides valuable insights into the science of ageing and rejuvenation. It inspires readers to reconsider their perception of ageing and advocates for advancements in biomedical technologies.
This thought-provoking book is recommended for scientists, researchers, and individuals interested in the possibilities of longer and healthier lifespans.
The majority of scientists studying ageing biology believe that we will eventually be able to significantly slow down the ageing process, allowing us to live longer and more youthful lives. Dr. Aubrey de Grey is particularly optimistic about this possibility. Dr. de Grey envisions a biomedical technology that can not only slow down ageing-related decline but also reverse it periodically, keeping us biologically young for an extended and indefinite period of time.
In this review, we will take a closer look at Dr. de Grey’s perspective of ageing which he presents in his book ‘Ending Aging.’
About the authors
Aubrey de Grey, Ph.D., is a prominent figure in the field of gerontology and a leading advocate for the development of interventions to reverse the ageing process.
He is a chairman and chief science officer of the Methuselah Foundation, an organisation dedicated to advancing rejuvenation biotechnology. One of De Grey’s notable contributions is the formulation of a comprehensive plan called SENS (Strategies for Engineered Negligible Senescence). This plan aims to indefinitely postpone age-related physical and mental decline by addressing the underlying causes of ageing.
Michael Rae is Dr. de Grey’s research assistant. He has authored numerous scientific articles and commentaries published in respected peer-reviewed journals. Rae has a strong affiliation with the Calorie Restriction Society, where he has been a member for an extended period and previously served on the board. He has made significant contributions to society’s ‘How-to Guide’ and is a core scientific investigator involved in the Cohort Study. This study aims to investigate the feasibility of calorie restriction in humans and explore the potential anti-ageing effects observed in laboratory organisms.
What is the book about?
In ‘Ending Aging,’ Aubrey de Gray aims to shift the public perception of ageing from an inevitable part of life to a treatable disease. De Gray outlines seven primary causes of ageing and delves into the complexities of addressing them. His proposed approach lies between traditional gerontology (treating ageing-related diseases after their onset) and geriatrics (preventing diseases before they occur). Instead, he advocates for intervening just before accumulated damage transforms into a disease, aiming to cure the damage at that critical point.
The author highlights that the root cause of ageing is the gradual accumulation of damage within cells over time. The mitochondria, responsible for converting food into energy, are particularly susceptible to damage due to the constant supply of oxygen. Although cells have mechanisms to repair this damage, they eventually become overwhelmed, leading to ageing-related diseases.
Among the seven causes of ageing, the book touches on issues like glycation, lipofuscin, and AGE cross-links, all contributing to damage accumulation within and outside cells. The author compares the body to a car that can be continuously repaired over time, proposing that middle-aged individuals would be suitable candidates for these repair therapies.
De Gray discusses various potential methodologies for these repair therapies, including stem cells, gene therapies, drugs, and the significance of mouse rejuvenation experiments. He also emphasises the importance of maintaining good health through exercise and diet to live long enough to benefit from these therapies.
Key takeaways from ‘Ending Aging’
1. A cure for ageing lies in repair
While traditional medicine often focuses on symptom management through medication, it fails to tackle the underlying problems. Preventive measures are also limited when it comes to ageing due to the complex nature of the process.
Instead, the book proposes a different approach: repairing the accumulated damage caused by ageing. By starting the treatment of ageing at a certain point in life, such as 40 years old, and addressing the damage up to that point, one can potentially reset the biological age to a younger state. Continuously repairing and maintaining the body’s condition can then extend lifespan significantly.
Using this approach, a person who would have had a life expectancy of 80 years could potentially live up to 120 or even 160 years.
2. Mutations in mitochondria are a major factor in ageing
Free radicals, unstable atoms with unpaired electrons, are highly reactive and can cause damage to molecules within the body.
The mutations caused by free radicals in mitochondrial DNA contribute to accelerated ageing. To address this issue, the book suggests allotopic expression as a solution. Allotopic expression involves safeguarding a healthy backup copy of mitochondrial DNA in the nucleus of each cell. By doing so, the DNA is protected from exposure to free radicals, potentially preventing age-related damage.
3.The first step to winning the war against ageing is to change our mindset
The key takeaway from this book is the urgent need to shift our mindset and approach to anti-ageing treatments. While many promising interventions are still in the experimental stages, waiting for extensive funding and drug trials to be approved comes at a high cost. Aubrey de Grey argues that the time wasted in this process actually leads to more lives lost than the risks associated with experimental treatments.
The book highlights that for every person who may pass away due to an experimental drug, there are ten others who lose their lives because they had to wait too long for approved treatments.
The key message is that embracing some level of risk and accepting that not every treatment will succeed is crucial for advancing anti-ageing research. By overcoming the fear of failure and acknowledging that there may be casualties along the way, we can avoid unnecessary delays and propel the development of life-extending therapies, ultimately bringing us closer to a future without the limitations of ageing.
Strengths and weaknesses, according to readers’ reviews
Strengths:
• Provides a comprehensive overview of various forms of ageing and strategies to address them, making it a valuable primer in biology for readers without a strong background in the subject.
• Despite being published in 2007, the book still imparts significant knowledge, especially in the realm of biology, and helps readers catch up with current issues and developments in the field.
• The writing style is engaging and informative, with delightful analogies that aid in understanding complex biology concepts.
Weaknesses:
• The book is highly theoretical and delves into advanced biology, making it difficult for laypersons to understand, particularly in the second part where deep dives into scientific concepts are presented.
Best quotes from ‘Ending Aging’
“I have been aware for many years that most people do not think about aging in the same way that they think about cancer, or diabetes, or heart disease. They are strongly in favor of the absolute elimination of such diseases as soon as possible, but the idea of eliminating aging – maintaining truly youthful physical and mental function indefinitely – evokes an avalanche of fears and reservations. Yet, in the sense that matters most, aging is just like smoking: It’s really bad for you.”
“Science is about the testing and refinement of hypotheses and theories. In principle, the most important quality of a scientist should be their ability to accept, with an open mind, evidence that challenges theories that they had believed for many years. But scientists are human, and moreover they know that the scientists that produced the new evidence are also human. In particular, they know that when a result is reported that contradicts established conventional thinking, the new evidence is often found later on to have been the result of experimental error.”
“Every day of your life, the same processes that are involved in the browning of meats and other glazed or fried foods are insidiously at work in your body. In your arteries. In your kidneys. In your heart, your eyes, your skin, your nerves. At this very moment, in all your tissues, the sugar that provides your body with so much of its energy is also performing some unwanted chemical experiments, caramelizing your body through exactly the same processes that caramelize onions or peanut brittle. Slowly but steadily, unwanted bonding by sugars and fats handcuffs your proteins, inactivates your enzymes, triggers unhealthy chemical signals in your cells, and damages your DNA. Aging you.”
Final takeaway
‘Ending Aging’ by Aubrey de Grey offers a compelling perspective on slowing down and reversing the ageing process. The book provides valuable insights into the science of ageing and rejuvenation. It inspires readers to reconsider their perception of ageing and advocates for advancements in biomedical technologies.
This thought-provoking book is recommended for scientists, researchers, and individuals interested in the possibilities of longer and healthier lifespans.
October 14, 2019
This was a good book, but beware: It is probably too technical for the layperson.
Aubrey de Grey believes that aging can be defeated. In the book, he describes aging as an inevitable side-effect of our biological processes and metabolic pathways. That we accumulate "damage" from the normal operation of our bodily processes.
He makes the case that we can overcome aging with biological "maintenance". He uses the analogy that hundred year old cars are still operational, if they have been maintained property. Ditto 500+ year old buildings.
In the first part of the book, he lays out his basic rationale for this thesis. In the second part, he takes a deep dive into the science behind his position. In the conclusion, he states that more research is needed, and makes an appeal for funding.
The concepts presented here are interesting, and I agree that his research is important.
As mentioned at the start, however, I found this book to be extremely technical. If you don't have a decent grasp of intermediate biology, most of what he talks about in the second part onwards is going to sound like Greek to you.
"Ending Aging" is one of those science books written by a scientist, for scientists.
If Aubrey and this topic interest you, but you don't have a firm grasp of advanced biology, you might get more from his talks online. He does a ~1hr talk at Google that was a good primer to his views.
So while this was a good and comprehensive book on the topic of aging, it will unfortunately not find an audience with most of the general public.
For that reason, I am rating it 3 stars.
Aubrey de Grey believes that aging can be defeated. In the book, he describes aging as an inevitable side-effect of our biological processes and metabolic pathways. That we accumulate "damage" from the normal operation of our bodily processes.
He makes the case that we can overcome aging with biological "maintenance". He uses the analogy that hundred year old cars are still operational, if they have been maintained property. Ditto 500+ year old buildings.
In the first part of the book, he lays out his basic rationale for this thesis. In the second part, he takes a deep dive into the science behind his position. In the conclusion, he states that more research is needed, and makes an appeal for funding.
The concepts presented here are interesting, and I agree that his research is important.
As mentioned at the start, however, I found this book to be extremely technical. If you don't have a decent grasp of intermediate biology, most of what he talks about in the second part onwards is going to sound like Greek to you.
"Ending Aging" is one of those science books written by a scientist, for scientists.
If Aubrey and this topic interest you, but you don't have a firm grasp of advanced biology, you might get more from his talks online. He does a ~1hr talk at Google that was a good primer to his views.
So while this was a good and comprehensive book on the topic of aging, it will unfortunately not find an audience with most of the general public.
For that reason, I am rating it 3 stars.
June 26, 2008
The only certainty is taxes, apparently.
Throughout human history, we have accepted the life of our parents as a template for our own lives. In concious ways, but also in unconcious ways. Like the inevitability of death. But we will be forced to re-evaluate even that, it seems.
This chatty british author fires the first shot over the bow. There will be better authors to cover the subject (Gladwell? Please?), but DeGrey got here first. And he's maybe a bit condescending in how he 'exposes' our "pro-death-trance", but the technical content of the book is unquestionably valuable.
The one thing he does REALLY well is present medical vocabulary to the reader. Reading the book from beginning to end, the chapters subtely introduce terminology and concepts which are reinforced. I feel like I have 1% of a medical researcher degree now. They should staple a mini-certificate in the back of the book.
As to the question... will we end aging in your lifetime? I want to believe, but I'm unconvinced. As bill gates (or someone) said: People always achieve less than they predict on the three year timescale, and more than they ever imagined possible on a 10 year timescale. So... 30 years is plausible to me.
I'll let you know my continuing thoughts on the subject.
Throughout human history, we have accepted the life of our parents as a template for our own lives. In concious ways, but also in unconcious ways. Like the inevitability of death. But we will be forced to re-evaluate even that, it seems.
This chatty british author fires the first shot over the bow. There will be better authors to cover the subject (Gladwell? Please?), but DeGrey got here first. And he's maybe a bit condescending in how he 'exposes' our "pro-death-trance", but the technical content of the book is unquestionably valuable.
The one thing he does REALLY well is present medical vocabulary to the reader. Reading the book from beginning to end, the chapters subtely introduce terminology and concepts which are reinforced. I feel like I have 1% of a medical researcher degree now. They should staple a mini-certificate in the back of the book.
As to the question... will we end aging in your lifetime? I want to believe, but I'm unconvinced. As bill gates (or someone) said: People always achieve less than they predict on the three year timescale, and more than they ever imagined possible on a 10 year timescale. So... 30 years is plausible to me.
I'll let you know my continuing thoughts on the subject.
April 10, 2019
This book changed the way I view aging, from something inevitable (which to be fair it always has been), to something that is an engineering challenge to be fixed.
It's not just about increasing lifespan, it's about maintaining your health as you age (healthspan).
The beginning and end of the book explain the psychology, biology and rationale for the approach to end aging.
The middle goes deep into some of the science around the 7 areas of accumulative aging damage to tackle. You can probably skip through all that and still get a lot from the book.
Coupling this damage repair with molecules (pill form) that increase protective pathways (think Metformin and Rapamycin, but better), and there's a good chance our children's generation will live comfortably beyond 100.
Even if you don't believe at all in preventing aging, this approach will still yeild results in tacking diseases like Alzheimer's and cardiovascular disease.
Probably the two most exciting treatments in the works are senolytic drugs (to remove senescent cells which increase inflammation) and the use of Yamanaka factors to rejuvenate cells. Excited to see where things go from here!
It's not just about increasing lifespan, it's about maintaining your health as you age (healthspan).
The beginning and end of the book explain the psychology, biology and rationale for the approach to end aging.
The middle goes deep into some of the science around the 7 areas of accumulative aging damage to tackle. You can probably skip through all that and still get a lot from the book.
Coupling this damage repair with molecules (pill form) that increase protective pathways (think Metformin and Rapamycin, but better), and there's a good chance our children's generation will live comfortably beyond 100.
Even if you don't believe at all in preventing aging, this approach will still yeild results in tacking diseases like Alzheimer's and cardiovascular disease.
Probably the two most exciting treatments in the works are senolytic drugs (to remove senescent cells which increase inflammation) and the use of Yamanaka factors to rejuvenate cells. Excited to see where things go from here!
August 6, 2021
Easily 5/5 stars. One of my all-time favorites.
This book is extremely informative, and the writing and writing style are great, with numerous delightful helpful analogies to explain the biology.
I don't know how well it would fit people with different backgrounds in biology, but it was pretty much perfect for me at this time.
There is a relatively short section that discusses science-politics instead of the science itself, but the rest of the book easily makes up for that. Also, I suspect the section about the immune system is somewhat out-dated, but I guess it is pretty educating to learn about past misunderstandings of the scientific community.
Maybe the most impressive for me was the multiple highly thought provoking hypotheses and ideas introduced in the book. To name a few: a roadmap to eliminate aging; "the new mitochondrial free radical theory of aging"; and an audacious method to prevent cancer.
This book is extremely informative, and the writing and writing style are great, with numerous delightful helpful analogies to explain the biology.
I don't know how well it would fit people with different backgrounds in biology, but it was pretty much perfect for me at this time.
There is a relatively short section that discusses science-politics instead of the science itself, but the rest of the book easily makes up for that. Also, I suspect the section about the immune system is somewhat out-dated, but I guess it is pretty educating to learn about past misunderstandings of the scientific community.
Maybe the most impressive for me was the multiple highly thought provoking hypotheses and ideas introduced in the book. To name a few: a roadmap to eliminate aging; "the new mitochondrial free radical theory of aging"; and an audacious method to prevent cancer.
September 9, 2019
I'm having trouble rating this book. I don't have the knowledge to evaluate the information provided as most of the biology and chemistry is well above my head. I decided to give it the rare 5 stars because I can't think of many or even any subjects more important than the one in this book. I wish everyone will read it and get infected with Aubrey de Grey's enthusiasm for a better future.
About the book itself, I had a "holly shit!" moment when he described that one scientist didn't want to be associated with the research because she was afraid it would work and the implications. Wow.
I found the analogies used to describe the different biological and chemistry processes cute and helpful.
About the book itself, I had a "holly shit!" moment when he described that one scientist didn't want to be associated with the research because she was afraid it would work and the implications. Wow.
I found the analogies used to describe the different biological and chemistry processes cute and helpful.
January 19, 2021
Aubrey De Grey is on a mission to break the spell that pervaded our culture: the pro-aging trance. Over the millenias, a lot of attempts to reach immortality and prolong lives have failed and it has been percolating through the generations the notion that Death is inevitable and part of life and there is just nothing that can be done about it. We should strive to make the most of the few "meaningful" decades we have on this earth and that is that.
The author begs to differ, and he wrote an entire book to rekindle the hope in a future where people live up to the healthy age of 1000 years old. Wat!?
The author founded the organization SENS, with the puropse of solving aging and extending the span of healthy lives for a couple of decade in the short tern, and indefinitely in the long term.
The author identify 7 causes of aging that engender the accumulaion of damage over the years until the onset of aging diseases. The author argues that the best approach to solving aging would be to take the intermediate approach between Gerontology( Curing the diseases of aging after their occurence) and Geriatrics( preventing the diseases of aging before they happen). The said apprach would consist of curing the accumulated damage just before it transforms into a disease.
Now the reason behind choosing this approach is that in order to prevent a disease from happening one needs to understand very complex mechanisms of how damage accumulates and there is just so much that needs be understood on the molecular level to prevent the disease,plus prevention therapies extend life at the best of cases only for a decade or two. So it is a hard endeavour to take and not worth the bang for the buck. Solving the disease after it has happened wouldn't give more than couple of years of extended life and it is not recommended that one messes with the metabolism of the body, not to mention the side effects on healthy cells caused by applying this approach.
Okay, let's get this straight. Death of mamallians is caused by the diseases of aging from cancer to heart attacks to dementia and all the rest. What causes the diaeases of aging? It is the accumulated damage over the years; being alive for a long time is apparently bad for your health. At the cellular level,what is happening throughout the breathing you're doing right now is that the mitochondria,an organelle that transforms food into ATP, fuel for the body, is accumulating damage slowly but surely, thanks to the constant supply of oxygen that is facilitating the process. To be sure, the cells have mechanisms of their own to repair this accumulated damage until well into your 30s, but at one point, the damage to the cell catches up with the cell's ability to repair it and it becomes dangerous. One of the products of our metabolism is free radicals, which is deemed one of the contributors of aging. It originates through the mutation of mitochondira. There are a lot of arguments surronding how big of a role the mitochondrial mutation has in aging but let's not dwell on that.
Among the 7 causes of aging we hear terms like Glycation( has to do with sugar not working proberly or something), lipofuscin( sparkly stuff which were found to be consumed by novel bacterias liviing in cemetaries. The author talks about extracting cells from these bacteria and injecting it in humans so that lipofuscins are eliminated before death), AGE cross-links; again, repair mechanisms in cellls getting overwhemed by the garbage which becomes increasingly difficult to handle with age. There are also things like stiffening of the tissues which makes it hard for blood to flow into arteries with age, but at the end of the day it all boils down to damage accumulation inside amd outside the cell which is programmed to function properly till the age where the individual has had enough time to reproduce.
The author think of the body as a car that can be repaired continuously over time. In the case of humans, we will be able to repair the damage accumulated by aging every couple of decades or so, provided we start with middle aged men( our intermediate approach), apparently the perfect age group to undergo these repairs.
As to the methodology behind the repairs, the author mentions therapies conducted with the help of stem cells( cells that can take any shape or form in the body); embryonic stem cell, somatic nuclear transfer cell, gene therapies, drugs, mouse rejuvenation something something_ apparently mouse rejuvenation is a very important milestone to achieve_.
The author talks about calorie restricion as a natural method to slow aging,albeit to a limited degree. Also mentioned were various different types of drugs amd vaccines.
In order to reach the future of eternal youth, the author suggests that we take care of our health as much as we can through excercice,diet, and all the rest to live enough to take these therapies. Equally important is the use of lobbying amd donating to accelerate the progress of these therapies.
Ideally,the author wants therapies to start as soon as 2030 and then every couple decades you go back and do some more therpaies, ad infinitum.
I learned a lot from this book,and I think I can now see why talking about progress in longevity is not empty talk but rather based on sound reasoning. But still,I can not but feel doubtful of the success of as big an endeavour as solving aging once and for all.
I leave this book with an immense sense of excitement for a future devoid of suffering and age related diseases and maybe eternal youth? I don't know what is possible anymore.
The author begs to differ, and he wrote an entire book to rekindle the hope in a future where people live up to the healthy age of 1000 years old. Wat!?
The author founded the organization SENS, with the puropse of solving aging and extending the span of healthy lives for a couple of decade in the short tern, and indefinitely in the long term.
The author identify 7 causes of aging that engender the accumulaion of damage over the years until the onset of aging diseases. The author argues that the best approach to solving aging would be to take the intermediate approach between Gerontology( Curing the diseases of aging after their occurence) and Geriatrics( preventing the diseases of aging before they happen). The said apprach would consist of curing the accumulated damage just before it transforms into a disease.
Now the reason behind choosing this approach is that in order to prevent a disease from happening one needs to understand very complex mechanisms of how damage accumulates and there is just so much that needs be understood on the molecular level to prevent the disease,plus prevention therapies extend life at the best of cases only for a decade or two. So it is a hard endeavour to take and not worth the bang for the buck. Solving the disease after it has happened wouldn't give more than couple of years of extended life and it is not recommended that one messes with the metabolism of the body, not to mention the side effects on healthy cells caused by applying this approach.
Okay, let's get this straight. Death of mamallians is caused by the diseases of aging from cancer to heart attacks to dementia and all the rest. What causes the diaeases of aging? It is the accumulated damage over the years; being alive for a long time is apparently bad for your health. At the cellular level,what is happening throughout the breathing you're doing right now is that the mitochondria,an organelle that transforms food into ATP, fuel for the body, is accumulating damage slowly but surely, thanks to the constant supply of oxygen that is facilitating the process. To be sure, the cells have mechanisms of their own to repair this accumulated damage until well into your 30s, but at one point, the damage to the cell catches up with the cell's ability to repair it and it becomes dangerous. One of the products of our metabolism is free radicals, which is deemed one of the contributors of aging. It originates through the mutation of mitochondira. There are a lot of arguments surronding how big of a role the mitochondrial mutation has in aging but let's not dwell on that.
Among the 7 causes of aging we hear terms like Glycation( has to do with sugar not working proberly or something), lipofuscin( sparkly stuff which were found to be consumed by novel bacterias liviing in cemetaries. The author talks about extracting cells from these bacteria and injecting it in humans so that lipofuscins are eliminated before death), AGE cross-links; again, repair mechanisms in cellls getting overwhemed by the garbage which becomes increasingly difficult to handle with age. There are also things like stiffening of the tissues which makes it hard for blood to flow into arteries with age, but at the end of the day it all boils down to damage accumulation inside amd outside the cell which is programmed to function properly till the age where the individual has had enough time to reproduce.
The author think of the body as a car that can be repaired continuously over time. In the case of humans, we will be able to repair the damage accumulated by aging every couple of decades or so, provided we start with middle aged men( our intermediate approach), apparently the perfect age group to undergo these repairs.
As to the methodology behind the repairs, the author mentions therapies conducted with the help of stem cells( cells that can take any shape or form in the body); embryonic stem cell, somatic nuclear transfer cell, gene therapies, drugs, mouse rejuvenation something something_ apparently mouse rejuvenation is a very important milestone to achieve_.
The author talks about calorie restricion as a natural method to slow aging,albeit to a limited degree. Also mentioned were various different types of drugs amd vaccines.
In order to reach the future of eternal youth, the author suggests that we take care of our health as much as we can through excercice,diet, and all the rest to live enough to take these therapies. Equally important is the use of lobbying amd donating to accelerate the progress of these therapies.
Ideally,the author wants therapies to start as soon as 2030 and then every couple decades you go back and do some more therpaies, ad infinitum.
I learned a lot from this book,and I think I can now see why talking about progress in longevity is not empty talk but rather based on sound reasoning. But still,I can not but feel doubtful of the success of as big an endeavour as solving aging once and for all.
I leave this book with an immense sense of excitement for a future devoid of suffering and age related diseases and maybe eternal youth? I don't know what is possible anymore.
July 25, 2020
A fascinating look at several methods of life-lengthening and death-defeating research. A lot of the details about the intricate processes in this book went over my head, but the majority of it was very interesting. As someone who isn't at all knowledgeable in this field, it's impossible for me to say whether he makes a legitimate case for his methods' effectiveness or not, but it's encouraging that someone is trying to tackle the biggest health problem of all — one that doesn't even seem to occur to most people.
June 18, 2018
Metabolic processes in our bodies are merely chemical reactions. The aging phenomenon is caused by the accumulation of damage to biological structures and the induced state of dysfunctional cells. Strategies to reverse such damage on a cellular level are plausible and such efforts deserve more research funding and awareness. A great introductory book for anyone seeking answers to a scientifically possible equivalent of the Fountain of Youth.
January 2, 2017
Inspiring read, I've read a few articles about separate concerns mentioned throughout the book, but most of all I couldn't help but circle back on the implications of a significant extension of life and what that would mean for our species here on earth (and/or elsewhere)
December 25, 2016
Amazing. The book gets technical at times for light reading, but I appreciate the confidence. Some very exciting ideas in this book!
March 18, 2011
Die ewige Jugend - ein Thema, wie aus dem Märchenbuch. Doch kein Thema, welches im Märchenbuch bleiben muss, wie Aubrey de Grey in seinem Buch "Niemals alt!" (englische Originalversion: "Ending Aging") schlüssig darlegt.
Das Buch beginnt mit einer Diskussion, worauf der Begriff "Altern" eigentlich abzielt und was konkret den Alterungsprozess ausmacht, wo man also eingreifen könnte, um das Altern zu verhindern. Mit der Analogie zu einem Oldtimer illustriert Grey seinen Ansatz in Bezug auf die Alterung, einen Ansatz, den er den "Ingenieuer-Ansatz" getauft hat: Die Idee ist, dass man nicht die Stoffwechselprozesse, die zur Alterung führen korrigieren muss - das ist viel zu kompliziert und dürfte in den nächsten Jahrzehnten ohne gigantische Nebenwirkungen nicht möglich sein. Aber zum Glück geht es eben auch anders: Man kann nämlich die Schäden, die sich als Ergebnis des Prozesses der Alterung im Körper ansammeln, "eliminieren" um so einem alten Menschen wieder einen biologisch jugendlichen Körper zu verschaffen. Grey behauptet, dass es nur sieben zentrale Arten dieser Schäden gibt: Zellverlust, extrazellulärer Müll, Glykalisation, Seneszente Zellen, Mitochondriale Mutationen und Krebs. Im den nächsten Kapiteln widmet er sich jeweils einem dieser Schäden und erklärt die komplexen Stoffwechselzusammenhänge, die ihn zu der Annahme verleiteten, eben dieser Schaden sei für die Alterung verantwortlich. Außerdem erläutert er natürlich, wie sich dieser Schaden beheben lässt (auch wenn sich nach der Behebung erneut Schaden ansammeln wird, so dass die Behandlung alle paar Zeiteinheiten wiederholt werden muss).
Es geht los mit dem meiner Meinung nach faszinierendsten Thema des Buches, nämlich der Diskussion, wie Mutationen an der mitochondrialen DNA zur Alterung beitragen. Das funktioniert folgendermaßen: Mitochondrien, bekannterweise die Kraftwerke der Zellen, sind als Nebenwirkung ihrer Tätigkeit einer großen Menge an freien Radikalen ausgesetzt, die zu Mutationen in ihrer DNA führen. Das könnte einen jetzt zu der Annahme verleiten, dass Mitochondrien mit der Zeit immer schlechter in ihrer Energieproduktion werden - weil sie weniger Energie produzieren, altern wir. Logisch, oder? Schon logisch, aber komplett falsch. Warum falsch? Weil es nicht mit den Ergebnissen übereinstimmt, die klar aufzeigen, dass Mitochondrien nur in einigen wenigen Körperzellen in die Fehlfunktion abgleiten, dort dann aber ein totales Disaster anrichten und auch umgebenden Zellen noch Schaden zufügen. Wie kann das sein? Die Erklärung liegt in einer vom Lysosym bedingten Mikroevolution der Mitochondrien: Mitochondrien die als Folge ihrer Nähe zu freien Radikalen in ihrer Membran zerfetzt werden (und somit nicht mehr ihre Aufgabe wahrnehmen können) werden automatisch vom Lysosym entsorgt. Theoretisch müsste das aber auf alle Mitochondrien zutreffen, denn der Menge an freien Radikalen, der sie ausgesetzt sind, widersteht kein Zellorganell auf lange Zeit. Aber manche Mitochondrien haben einen Trick angewendet und sind so mutiert, dass sie einfach keine Energie mehr produzieren: da die Quelle der freien Radikale ihre Energieproduktion ist werden sie nie zerfetzt und demnach auch nie vom Lysosym entsorgt. Sie haben sich perfekt an ihre Situation angepasst - das Überleben der Betrüger.
Gibt es für dieses Problem eine Lösung? Aber sicher: Man kann die Mitochondrien-DNA in den Zellkern transferieren, so dass Mutationen nicht ohne Weiteres stattfinden können. Tatsächlich hat Mutter Natur das anscheinend schon mit dem Großteil der Mitochondrien-DNA so gemacht - das weißt allerdings daraufhin, dass es für den Rest nicht so einfach werden könnte. Hier gilt aber auch Yudkowsky's Spruch: Der Mensch ist intelligenter als die Evolution. Außerdem finden sich bereits in anderen Tierarten Gene, die manche der von der Mitochondrien-DNA codierten Proteine als Folge der Proteinbiosynthese der DNA herstellen würden. Es gibt noch ein paar zusätzliche Komplikationen, z.B. weil die entsprechenden Proteine hydrophob sind und somit auf dem Weg vom Zellkern ins Mitochondrium verkleben könnten - es gibt aber ebenfalls mehr als genug Ideen, wie man diese Probleme lösen könnte (z.B. durch die Codierung von Genen, die die Proteinbiosynthese dieses Genes erst direkt vor der Mitochondrien-Membran durchführen würden, so dass die Proteine noch während ihrer Herstellung in das Mitochondrium eintreten könnten).
Die nächste Art von Alters-Schäden, die besprochen wird, ist der innerzelluläre Müll. Warum wird der nicht abgebaut? Wird er ja, zumindest der Großteil, und zwar vom eben schon kurz erwähnten Lysosym. Das Problem ist jetzt, dass manche Arten von Müll einfach nicht von den im Lysosym vorhandenen Proteinen zersetzt werden können. Dieser Müll ist für viele schreckliche Krankheiten wie Arteriosklerose oder viele Arten der Neurodegeneration verantwortlich. Die Idee, wie man dieses Problem lösen könnte, stammt aus dem Bereich der Bioremediation, die schon lange natürlich vorkommende Bakterien und deren Enzyme nutzt, um bestimmte Arten von Giftmüll gefahrlos abzubauen. Die Herausforderung bleibt, Enzyme zu isolieren, die entsprechende, vom Lysosym nicht abgebaute Stoffe zersetzen können, und dann diese Enzyme nicht nur in die Zelle sondern direkt in das Lysosym zu schaffen, ohne das schädliche Nebenwirkungen auftreten. Wider gibt es genügend Ideen, die einzelnen Probleme anzugehen (z.B. könnte man das System ausnutzen, dass allen Müll in der Zelle zum Lysosym verfrachtet), und sonst alternative Lösungsansätze (z.B. könnte man die DNA so verändern, dass die entsprechenden Enzyme automatisch Teil der Lysoyme werden).
Es geht weiter mit extrazellulärem Abfall. Der prominenteste Vertreter dieser Kategorie ist Beta-Amyloid, dass (vermutlich) für Alzheimer verantwortlich ist. Wie kann man dieses "Plaques" zerstören? Eine Idee ist, dass Immunsystem dafür zu Hilfe zu ziehen, entweder indem man es mit entsprechenden Substanzen impft, die zur Bildung von Antikörpern gegen Amyloide im allgemeinen (denn auch die anderen sind "Böse") führt. Oder indem man die Antikörper selbst injiziert, eventuell besser, weil Studien die Gefahr einer zu allgemeinen Immunantwort auf den Impfstoff aufgezeigt haben - Gehirnentzündungen als Nebenwirkungen sind nicht akzeptabel. (Andererseits erwähnt der Autor im Nachwort, dass nach neueren Erkenntnissen die Gehirnentzündung auch gut das Produkt eines Trägerstoffes und nicht der eigentlichen Impfsubstanz gewesen sein könnte - was erklären würde, warum nur die menschliche Testgruppe Nebenwirkungen erlitt, während z.B. Mäuse verschont blieben).
Die nächste Gefahr für den Körper sind sogenannte AGEs, "Advanced Glycation End-Products", also die fortgeschrittenen Endprodukte der Glykation. Diese AGEs sind das Produkt der Existenz von Zucker in unserem Blut, der eben zum Verkleben von wichtigen Proteinen führt. Diese AGEs können eventuell von entsprechenden Enzymen bzw. Spalt-Proteinen gespalten und damit in eine ungefährliche Form überführt werden - ein Medikament mit diesem Ziel, Alagebrium, wird bereits getestet.
Ebenfalls nicht zu unterschätzen sind mehrere Arten von toten, seneszenten oder überflüssigen und schadhaften Zellen. Zum Beispiel hat der Verlust der Stärke des Immunsystems bei älteren Menschen hauptsächlich mit einer Überspezialisierung gewisser Immunzellen zu tun: Weil jeder von uns latente Krankheiten mit sich führt stellt das Immunsystem gegen diese Krankheiten nicht nur spezialisierte Zellen her, sondern lässt diese auch am Leben statt sie zu zerstören. Da aber das "Budget" des Immun-Systems begrenzt ist, führt das dazu, dass weniger unspezialisierte Zellen vorhanden sind. Noch schlimmer: Die spezialisierten Zellen funktionieren nach einer Weile noch nicht mal in ihrem begrenzten Anwendungsraum. Solche Zellen und andere (z.B. viscerales Fett) müssen weg. Das Hauptproblem ist hier das Erkennen von solchen Zellen, damit eine Therapie gezielt nur diese und keine gesunden Zerstören kann. Hier lassen sich Analogien zu bereits vorhandenen Krebs-Therapien ausbauen, die insbesondere auch schon bei der Zerstörung von Zellen gut fortgeschritten sind. Trotzdem muss weiter an der Erkennung dieser Zellen gearbeitet werden...
Zellen ersetzen: Manche Zellen gehen uns einfach im Leben verloren, ohne dass der Körper sie selber ersetzen kann. Die rettende Idee kommt hier aus der Stammzellen-Forschung, die es theoretisch ermöglicht, per therapeutischem Klonen (oder neuerdings auch durch moralisch weniger umstrittene Prozesse zur Herstellung von sogenannten iPS-Zellen aus Hautzellen) und nachträglicher Differenzierung der Zellen jede Zelle, die benötigt werden könnte, herzustellen.
Bleibt nur noch Krebs: Laut Grey ist die einzige umfassende Lösung zur Verhinderung der Entstehung kritischer Tumore die Entfernung von sämtlicher Telomerase aus dem Körper, bzw. wenigstens der Telomerase-exprimierenden Gene in der menschlichen DNA. Telomerase ist das Einzige, was Krebszellen ihr exponentielles Wachstum ermöglicht, indem es die Telomere, die die Anzahl der Zellteilungen normalerweise beschränken würden, nachfüllt. Leider benötigen wir Telomerase auch in wichtigen anderen Zellen. Grey schlägt hier sein radikales WILT Program vor: Wenn wir es bereits geschafft haben, die entwschwundenen Zellen durch nachträglich gewonnene und differenzierte Stammzellen zu ersetzen, so können wir das auch mit den Zellen tun, die sich eigentlich per Telomerase unendlich teilen können. Wir geben ihnen halt lange Telomere, und sobald die zu kurz werden, ersetzen wir sie einfach durch neu-gewonnene Zellen, die erneut lange Telomere haben. Das ist radikal, aber vielleicht die einzige Möglichkeit, das zunehmende Vorkommen von Krebs im Alter zu verhindern.
Das Buch schließt mit einigen Bemerkungen dazu, wann solche Therapien wahrscheinlich entstehen könnten, und vor allen Dingen mit der Idee der Longevity-Escape-Velocity. Wichtig ist laut Grey aber auch das Überkommen der Pro-Aging-Trance, in der sich momentan der Großteil der Gesellschaft befindet. Ernsthafte Forschungsfortschritte sind erst mit einer Menge an Staatsmitteln zu erreichen, die erst bei allgemeiner Akzeptanz der Idee der rapid life extension zu erwarten sind. Er selber hat dazu den MPrize ins Leben gerufen. Diese Diskussion hat mich auch an die Idee der ProAging-Argumentation als Cached Thought erinnert.
Alles in allem ein sehr spannendes, wenn auch teilweise sehr kompliziertes und langwieriges Buch über ein Thema, was eigentlich jeden interessieren sollte. Wenn man sich wenigstens noch ein bisschen an den Biologie GK aus der Oberstufe erinnert: lesen. Wenn nicht: Biobuch aus der Oberstufe holen, lesen. Dann dieses Buch lesen!
Das Buch beginnt mit einer Diskussion, worauf der Begriff "Altern" eigentlich abzielt und was konkret den Alterungsprozess ausmacht, wo man also eingreifen könnte, um das Altern zu verhindern. Mit der Analogie zu einem Oldtimer illustriert Grey seinen Ansatz in Bezug auf die Alterung, einen Ansatz, den er den "Ingenieuer-Ansatz" getauft hat: Die Idee ist, dass man nicht die Stoffwechselprozesse, die zur Alterung führen korrigieren muss - das ist viel zu kompliziert und dürfte in den nächsten Jahrzehnten ohne gigantische Nebenwirkungen nicht möglich sein. Aber zum Glück geht es eben auch anders: Man kann nämlich die Schäden, die sich als Ergebnis des Prozesses der Alterung im Körper ansammeln, "eliminieren" um so einem alten Menschen wieder einen biologisch jugendlichen Körper zu verschaffen. Grey behauptet, dass es nur sieben zentrale Arten dieser Schäden gibt: Zellverlust, extrazellulärer Müll, Glykalisation, Seneszente Zellen, Mitochondriale Mutationen und Krebs. Im den nächsten Kapiteln widmet er sich jeweils einem dieser Schäden und erklärt die komplexen Stoffwechselzusammenhänge, die ihn zu der Annahme verleiteten, eben dieser Schaden sei für die Alterung verantwortlich. Außerdem erläutert er natürlich, wie sich dieser Schaden beheben lässt (auch wenn sich nach der Behebung erneut Schaden ansammeln wird, so dass die Behandlung alle paar Zeiteinheiten wiederholt werden muss).
Es geht los mit dem meiner Meinung nach faszinierendsten Thema des Buches, nämlich der Diskussion, wie Mutationen an der mitochondrialen DNA zur Alterung beitragen. Das funktioniert folgendermaßen: Mitochondrien, bekannterweise die Kraftwerke der Zellen, sind als Nebenwirkung ihrer Tätigkeit einer großen Menge an freien Radikalen ausgesetzt, die zu Mutationen in ihrer DNA führen. Das könnte einen jetzt zu der Annahme verleiten, dass Mitochondrien mit der Zeit immer schlechter in ihrer Energieproduktion werden - weil sie weniger Energie produzieren, altern wir. Logisch, oder? Schon logisch, aber komplett falsch. Warum falsch? Weil es nicht mit den Ergebnissen übereinstimmt, die klar aufzeigen, dass Mitochondrien nur in einigen wenigen Körperzellen in die Fehlfunktion abgleiten, dort dann aber ein totales Disaster anrichten und auch umgebenden Zellen noch Schaden zufügen. Wie kann das sein? Die Erklärung liegt in einer vom Lysosym bedingten Mikroevolution der Mitochondrien: Mitochondrien die als Folge ihrer Nähe zu freien Radikalen in ihrer Membran zerfetzt werden (und somit nicht mehr ihre Aufgabe wahrnehmen können) werden automatisch vom Lysosym entsorgt. Theoretisch müsste das aber auf alle Mitochondrien zutreffen, denn der Menge an freien Radikalen, der sie ausgesetzt sind, widersteht kein Zellorganell auf lange Zeit. Aber manche Mitochondrien haben einen Trick angewendet und sind so mutiert, dass sie einfach keine Energie mehr produzieren: da die Quelle der freien Radikale ihre Energieproduktion ist werden sie nie zerfetzt und demnach auch nie vom Lysosym entsorgt. Sie haben sich perfekt an ihre Situation angepasst - das Überleben der Betrüger.
Gibt es für dieses Problem eine Lösung? Aber sicher: Man kann die Mitochondrien-DNA in den Zellkern transferieren, so dass Mutationen nicht ohne Weiteres stattfinden können. Tatsächlich hat Mutter Natur das anscheinend schon mit dem Großteil der Mitochondrien-DNA so gemacht - das weißt allerdings daraufhin, dass es für den Rest nicht so einfach werden könnte. Hier gilt aber auch Yudkowsky's Spruch: Der Mensch ist intelligenter als die Evolution. Außerdem finden sich bereits in anderen Tierarten Gene, die manche der von der Mitochondrien-DNA codierten Proteine als Folge der Proteinbiosynthese der DNA herstellen würden. Es gibt noch ein paar zusätzliche Komplikationen, z.B. weil die entsprechenden Proteine hydrophob sind und somit auf dem Weg vom Zellkern ins Mitochondrium verkleben könnten - es gibt aber ebenfalls mehr als genug Ideen, wie man diese Probleme lösen könnte (z.B. durch die Codierung von Genen, die die Proteinbiosynthese dieses Genes erst direkt vor der Mitochondrien-Membran durchführen würden, so dass die Proteine noch während ihrer Herstellung in das Mitochondrium eintreten könnten).
Die nächste Art von Alters-Schäden, die besprochen wird, ist der innerzelluläre Müll. Warum wird der nicht abgebaut? Wird er ja, zumindest der Großteil, und zwar vom eben schon kurz erwähnten Lysosym. Das Problem ist jetzt, dass manche Arten von Müll einfach nicht von den im Lysosym vorhandenen Proteinen zersetzt werden können. Dieser Müll ist für viele schreckliche Krankheiten wie Arteriosklerose oder viele Arten der Neurodegeneration verantwortlich. Die Idee, wie man dieses Problem lösen könnte, stammt aus dem Bereich der Bioremediation, die schon lange natürlich vorkommende Bakterien und deren Enzyme nutzt, um bestimmte Arten von Giftmüll gefahrlos abzubauen. Die Herausforderung bleibt, Enzyme zu isolieren, die entsprechende, vom Lysosym nicht abgebaute Stoffe zersetzen können, und dann diese Enzyme nicht nur in die Zelle sondern direkt in das Lysosym zu schaffen, ohne das schädliche Nebenwirkungen auftreten. Wider gibt es genügend Ideen, die einzelnen Probleme anzugehen (z.B. könnte man das System ausnutzen, dass allen Müll in der Zelle zum Lysosym verfrachtet), und sonst alternative Lösungsansätze (z.B. könnte man die DNA so verändern, dass die entsprechenden Enzyme automatisch Teil der Lysoyme werden).
Es geht weiter mit extrazellulärem Abfall. Der prominenteste Vertreter dieser Kategorie ist Beta-Amyloid, dass (vermutlich) für Alzheimer verantwortlich ist. Wie kann man dieses "Plaques" zerstören? Eine Idee ist, dass Immunsystem dafür zu Hilfe zu ziehen, entweder indem man es mit entsprechenden Substanzen impft, die zur Bildung von Antikörpern gegen Amyloide im allgemeinen (denn auch die anderen sind "Böse") führt. Oder indem man die Antikörper selbst injiziert, eventuell besser, weil Studien die Gefahr einer zu allgemeinen Immunantwort auf den Impfstoff aufgezeigt haben - Gehirnentzündungen als Nebenwirkungen sind nicht akzeptabel. (Andererseits erwähnt der Autor im Nachwort, dass nach neueren Erkenntnissen die Gehirnentzündung auch gut das Produkt eines Trägerstoffes und nicht der eigentlichen Impfsubstanz gewesen sein könnte - was erklären würde, warum nur die menschliche Testgruppe Nebenwirkungen erlitt, während z.B. Mäuse verschont blieben).
Die nächste Gefahr für den Körper sind sogenannte AGEs, "Advanced Glycation End-Products", also die fortgeschrittenen Endprodukte der Glykation. Diese AGEs sind das Produkt der Existenz von Zucker in unserem Blut, der eben zum Verkleben von wichtigen Proteinen führt. Diese AGEs können eventuell von entsprechenden Enzymen bzw. Spalt-Proteinen gespalten und damit in eine ungefährliche Form überführt werden - ein Medikament mit diesem Ziel, Alagebrium, wird bereits getestet.
Ebenfalls nicht zu unterschätzen sind mehrere Arten von toten, seneszenten oder überflüssigen und schadhaften Zellen. Zum Beispiel hat der Verlust der Stärke des Immunsystems bei älteren Menschen hauptsächlich mit einer Überspezialisierung gewisser Immunzellen zu tun: Weil jeder von uns latente Krankheiten mit sich führt stellt das Immunsystem gegen diese Krankheiten nicht nur spezialisierte Zellen her, sondern lässt diese auch am Leben statt sie zu zerstören. Da aber das "Budget" des Immun-Systems begrenzt ist, führt das dazu, dass weniger unspezialisierte Zellen vorhanden sind. Noch schlimmer: Die spezialisierten Zellen funktionieren nach einer Weile noch nicht mal in ihrem begrenzten Anwendungsraum. Solche Zellen und andere (z.B. viscerales Fett) müssen weg. Das Hauptproblem ist hier das Erkennen von solchen Zellen, damit eine Therapie gezielt nur diese und keine gesunden Zerstören kann. Hier lassen sich Analogien zu bereits vorhandenen Krebs-Therapien ausbauen, die insbesondere auch schon bei der Zerstörung von Zellen gut fortgeschritten sind. Trotzdem muss weiter an der Erkennung dieser Zellen gearbeitet werden...
Zellen ersetzen: Manche Zellen gehen uns einfach im Leben verloren, ohne dass der Körper sie selber ersetzen kann. Die rettende Idee kommt hier aus der Stammzellen-Forschung, die es theoretisch ermöglicht, per therapeutischem Klonen (oder neuerdings auch durch moralisch weniger umstrittene Prozesse zur Herstellung von sogenannten iPS-Zellen aus Hautzellen) und nachträglicher Differenzierung der Zellen jede Zelle, die benötigt werden könnte, herzustellen.
Bleibt nur noch Krebs: Laut Grey ist die einzige umfassende Lösung zur Verhinderung der Entstehung kritischer Tumore die Entfernung von sämtlicher Telomerase aus dem Körper, bzw. wenigstens der Telomerase-exprimierenden Gene in der menschlichen DNA. Telomerase ist das Einzige, was Krebszellen ihr exponentielles Wachstum ermöglicht, indem es die Telomere, die die Anzahl der Zellteilungen normalerweise beschränken würden, nachfüllt. Leider benötigen wir Telomerase auch in wichtigen anderen Zellen. Grey schlägt hier sein radikales WILT Program vor: Wenn wir es bereits geschafft haben, die entwschwundenen Zellen durch nachträglich gewonnene und differenzierte Stammzellen zu ersetzen, so können wir das auch mit den Zellen tun, die sich eigentlich per Telomerase unendlich teilen können. Wir geben ihnen halt lange Telomere, und sobald die zu kurz werden, ersetzen wir sie einfach durch neu-gewonnene Zellen, die erneut lange Telomere haben. Das ist radikal, aber vielleicht die einzige Möglichkeit, das zunehmende Vorkommen von Krebs im Alter zu verhindern.
Das Buch schließt mit einigen Bemerkungen dazu, wann solche Therapien wahrscheinlich entstehen könnten, und vor allen Dingen mit der Idee der Longevity-Escape-Velocity. Wichtig ist laut Grey aber auch das Überkommen der Pro-Aging-Trance, in der sich momentan der Großteil der Gesellschaft befindet. Ernsthafte Forschungsfortschritte sind erst mit einer Menge an Staatsmitteln zu erreichen, die erst bei allgemeiner Akzeptanz der Idee der rapid life extension zu erwarten sind. Er selber hat dazu den MPrize ins Leben gerufen. Diese Diskussion hat mich auch an die Idee der ProAging-Argumentation als Cached Thought erinnert.
Alles in allem ein sehr spannendes, wenn auch teilweise sehr kompliziertes und langwieriges Buch über ein Thema, was eigentlich jeden interessieren sollte. Wenn man sich wenigstens noch ein bisschen an den Biologie GK aus der Oberstufe erinnert: lesen. Wenn nicht: Biobuch aus der Oberstufe holen, lesen. Dann dieses Buch lesen!
July 27, 2018
I had read a few articles about de Grey before starting the book so I knew his basic ideas:
-Aging is an engineering problem.
-We need to fund research on "fixing" aging, not just "understanding" it.
Turns out I really didn't learn too much from the book.
First, I didn't find it very well written for a science book for the general public. He sounded far too defensive and querulous. Most importantly his ideas didn't flow smoothly.
Secondly, it was FAAR too dense with detailed biochemistry. I don't think this is really useful for the casual reader.
Fortunately, I had already read other links online so I knew:
-He believes that aging is caused by 7 specific types of damage.
-No scientists currently believe that we have the slightest clue how to effectively fix any of them or when we'll be able to do so.
So, in my opinion, this book might be good for someone with a very solid background in cell biology who wants to get a detailed look at his ideas, but I can't imagine that it's suitable for a casual reader who just wants to get a layman's overview.
Will these kind of ideas lead to significant extension of human lifespan in my lifetime? Let's say within the next 50 years?
It's really hard to say, but it definitely sounds possible, even if not plausible.
-Aging is an engineering problem.
-We need to fund research on "fixing" aging, not just "understanding" it.
Turns out I really didn't learn too much from the book.
First, I didn't find it very well written for a science book for the general public. He sounded far too defensive and querulous. Most importantly his ideas didn't flow smoothly.
Secondly, it was FAAR too dense with detailed biochemistry. I don't think this is really useful for the casual reader.
Fortunately, I had already read other links online so I knew:
-He believes that aging is caused by 7 specific types of damage.
-No scientists currently believe that we have the slightest clue how to effectively fix any of them or when we'll be able to do so.
So, in my opinion, this book might be good for someone with a very solid background in cell biology who wants to get a detailed look at his ideas, but I can't imagine that it's suitable for a casual reader who just wants to get a layman's overview.
Will these kind of ideas lead to significant extension of human lifespan in my lifetime? Let's say within the next 50 years?
It's really hard to say, but it definitely sounds possible, even if not plausible.
Displaying 1 - 30 of 83 reviews