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Ageless: The New Science of Getting Older Without Getting Old
With the help of science, could humans find a way to become old without getting elderly, a phenomenon otherwise known as "biological immortality"? In Ageless, Andrew Steele, research fellow at Britain's new and largest biomedical laboratory, the Francis Crick Institute, shows us that the answer lies at the cellular level. He takes us on a journey through the laboratories where scientists are studying every aspect of the cell--DNA, mitochondria, stem cells, our immune systems, even age genes that can lead to a tenfold increase in life span (in worms, anyway)--all in an effort to forestall or reverse the body's (currently!) inevitable decline. With clear writing and intellectual passion, Steele shines a spotlight on a revolution already under way and offers reality-based hope.
304 pages, Hardcover
First published December 29, 2020
639 people are currently reading
3,774 people want to read
About the author
Andrew Steele
2books52followersDr Andrew Steele is a scientist, writer and campaigner based in London. After a PhD in physics from the University of Oxford, Andrew decided that ageing was the single most important scientific challenge of our time, and switched fields to computational biology. He worked at the Francis Crick Institute, using machine learning to decode our DNA and predict heart attacks using patients� NHS medical records. He is now a full-time science writer and presenter.
Andrew has appeared on Discovery and the BBC, produces his own videos on YouTube and gives live talks ranging from lectures to science stand-up at the Hammersmith Apollo. He has also campaigned about science funding as Chair of Science is Vital and creator of Scienceogram.
Andrew has appeared on Discovery and the BBC, produces his own videos on YouTube and gives live talks ranging from lectures to science stand-up at the Hammersmith Apollo. He has also campaigned about science funding as Chair of Science is Vital and creator of Scienceogram.
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Displaying 1 - 30 of 200 reviews
January 21, 2021
This is a fascinating book for fellow science geeks, but it's not a book on how the reader is necessarily going to avoid aging. Steele is a scientist who takes us on a deep dive into the 9 reasons he says we age. He maintains that aging is not required and that if we can manipulate cells enough, it may be possible for people to never age in the future. That's the thing though, this is all futuristic stuff. It's all cell manipulation and promising technology. It is quite interesting, but I'm not even sure that I agree with him that our governments should be funding this research, as I really think it would end up being one more area where the rich benefited and life got even harder for the poor.
The very end of the book tells how to live a little longer in the meantime in order to hopefully extend your life enough to live in times when they can extend it more and then more. These are absolutely basic things we all know -- stop smoking, exercise, get sleep, etc. He says not to take supplements (even vitamins). The last one is "be born a woman."
I was surprised that Steele didn't go into other things we do know help extend life, like social contact. He also talked a lot about the length of telomeres and how that translates to life expectancy, but never mentions things like the fact that they've shown that growing up in an abusive home and other sources of stress actually shorten telomeres.
Then there's the giddy fascination he has with all the scientists who sew mice together to study how that affects them (for instance, sewing a young mouse to an older one to see if the old one benefits from sharing cells and such). He actually uses the word "shockingly" when he says this research mostly stopped 30 years ago, but then he happily tells us that a married couple of scientists have started doing it again. Then he tells us about the experiments they're doing on King Charles spaniels in order to try to develop anti-aging technology to sell to dog owners (apparently this breed ages quickly). He sees this all as wonderful science. I just felt sad.
It is an interesting book for those who just love learning. I found it very interesting, but not actually helpful on a personal level.
I read a digital ARC of this book via Net Galley.
The very end of the book tells how to live a little longer in the meantime in order to hopefully extend your life enough to live in times when they can extend it more and then more. These are absolutely basic things we all know -- stop smoking, exercise, get sleep, etc. He says not to take supplements (even vitamins). The last one is "be born a woman."
I was surprised that Steele didn't go into other things we do know help extend life, like social contact. He also talked a lot about the length of telomeres and how that translates to life expectancy, but never mentions things like the fact that they've shown that growing up in an abusive home and other sources of stress actually shorten telomeres.
Then there's the giddy fascination he has with all the scientists who sew mice together to study how that affects them (for instance, sewing a young mouse to an older one to see if the old one benefits from sharing cells and such). He actually uses the word "shockingly" when he says this research mostly stopped 30 years ago, but then he happily tells us that a married couple of scientists have started doing it again. Then he tells us about the experiments they're doing on King Charles spaniels in order to try to develop anti-aging technology to sell to dog owners (apparently this breed ages quickly). He sees this all as wonderful science. I just felt sad.
It is an interesting book for those who just love learning. I found it very interesting, but not actually helpful on a personal level.
I read a digital ARC of this book via Net Galley.
December 24, 2020
Why do we grow old? It’s a universally accepted part of the human experience. The fact that we are not immortal drives many of our decisions, whether conscious or not: do you want to spend your life in one country only? Single, or married? Chasing a career, and if so, in what? But biologists are investigating a different question � why do we age? And, crucially, can we stop it? InAgeless,computational biologist Andrew Steele reveals the science behind the most important biomedical question of our time: why we get old, and how we can stop it.
This is a fascinating, objective and deeply informative read all compiled into an accessible, well researched and eminently readable book. Steele tells it like it is about the ageing process and you can tell it has been written by a scholar with a profound interest and passion for the topic at hand. From what was known about ageing in prehistoric times, including its origins, through to why we age, where Steele explores DNA, genetics and disease-related reasons of why we age, and from treating ageing, through to the quest for a cure, this is a captivating and wholly engaging read.
Undoubtedly, Ageless is the definitive and most up-to-date work covering all aspects of ageing and its lengthy process and the conversational style made it a pleasure to pick up. Scientists continue to work on a cure for ageing and it would of course revolutionise our entire lives and the way we decide to live. Due to this pursuance, it's only a matter of time before there is a breakthrough. An authoritative and convincing argument that life extension is inevitable, Steele illustrates that it's a matter of when and not if. Highly recommended.
This is a fascinating, objective and deeply informative read all compiled into an accessible, well researched and eminently readable book. Steele tells it like it is about the ageing process and you can tell it has been written by a scholar with a profound interest and passion for the topic at hand. From what was known about ageing in prehistoric times, including its origins, through to why we age, where Steele explores DNA, genetics and disease-related reasons of why we age, and from treating ageing, through to the quest for a cure, this is a captivating and wholly engaging read.
Undoubtedly, Ageless is the definitive and most up-to-date work covering all aspects of ageing and its lengthy process and the conversational style made it a pleasure to pick up. Scientists continue to work on a cure for ageing and it would of course revolutionise our entire lives and the way we decide to live. Due to this pursuance, it's only a matter of time before there is a breakthrough. An authoritative and convincing argument that life extension is inevitable, Steele illustrates that it's a matter of when and not if. Highly recommended.
January 12, 2021
2nd book for 2021.
Fascinating deep-dive into the study of human ageing and many different medical techniques that are in various stages of development to slow and eventually reverse it.
Four-stars.
Fascinating deep-dive into the study of human ageing and many different medical techniques that are in various stages of development to slow and eventually reverse it.
Four-stars.
September 19, 2021
This is a fascinating book about the science behind ageing. The book takes a comprehensive look at research into the reasons why we age. I was particularly struck by how optimistic the author is, that some day the secrets of anti-ageing will be understood and ageing will be a thing of the past. It won't happen overnight. Right now, science is finding certain approaches to extend life--and more importantly, to extend healthy life. As each year passes, perhaps a few hours or days can be added to the average extent of life. At some point, each year will be accompanied by enough scientific advances to advance the average extent of life by a year--and the people alive at that time will essentially become ageless.
But this won't happen anytime soon. The reason is that ageing is a complex process. If one cause of ageing is discovered and bypassed, then a new cause will crop up. For example, in prehistorical times, cancer was rare--people did not live long enough for cancer to develop. The DNA in every cell incurs hundreds or thousands of mutations. Most of these mutations are not problematic. But those mutations that are a problem accumulate over the years, and eventually can contribute to cancer.
One way to fight cancer is to shorten the affected telomeres in the cells' DNA. But this is exactly what would be detrimental to the extent of life. There seems to be a delicate balance between long telomeres contributing to old age, and short telomeres which help to combat cancer.
Only a single chapter at the end of the book describes concrete measures we can take to extend our lives. And--you can guess what those measures are. They are not secrets. And, from my other reading about the so-called "blue zones", I wonder why the social connections are not highlighted among those measures.
I did not read this book--I listened to the audiobook, narrated by the author. This was a mistake. The author's voice is pleasant, with a British accent. But his diction is unclear, and the audio engineering is not up to par. I found it difficult to understand some sentences. I found myself rewinding a bit from time to time, to try to understand some of the words. (English is my native language.) So while I definitely recommend this book, I would not recommend the audiobook.
But this won't happen anytime soon. The reason is that ageing is a complex process. If one cause of ageing is discovered and bypassed, then a new cause will crop up. For example, in prehistorical times, cancer was rare--people did not live long enough for cancer to develop. The DNA in every cell incurs hundreds or thousands of mutations. Most of these mutations are not problematic. But those mutations that are a problem accumulate over the years, and eventually can contribute to cancer.
One way to fight cancer is to shorten the affected telomeres in the cells' DNA. But this is exactly what would be detrimental to the extent of life. There seems to be a delicate balance between long telomeres contributing to old age, and short telomeres which help to combat cancer.
Only a single chapter at the end of the book describes concrete measures we can take to extend our lives. And--you can guess what those measures are. They are not secrets. And, from my other reading about the so-called "blue zones", I wonder why the social connections are not highlighted among those measures.
I did not read this book--I listened to the audiobook, narrated by the author. This was a mistake. The author's voice is pleasant, with a British accent. But his diction is unclear, and the audio engineering is not up to par. I found it difficult to understand some sentences. I found myself rewinding a bit from time to time, to try to understand some of the words. (English is my native language.) So while I definitely recommend this book, I would not recommend the audiobook.
February 12, 2022
My new goal in life is to become a Galapagos Tortoise.
February 1, 2024
A refreshing take on the age old question: How can I be young and fit forever?
Our society loves to combat aging with creams, herbs, and supplements. Yet at the end of the day, or more specifically- at the end of a life, we accept that aging is an inevitable process in the steady race to death.
Biogerontologists such as Andrew Steele refuse to accept this reality. No one really “dies of old age.� Rather, people experience an accumulation of cell damage and changes that inhibits the body’s ability to maintain homeostasis, leading to a reduction in immune response against diseases and maladies, which in turn leads to death of the organism.
To Steele, aging is a disease that must be defeated. He presents a fascinating overview of the field of biogerontology in three parts: The history of aging, gerontology, and why we age; the past, current, and future of the fight against aging; how to live longer based on research done so far, and where research and technology will soon meet medicine.
The book itself is well written and organized. Steele is also a bit of a personality, he has a Youtube channel and clearly knows how to present facts in a fun and interesting way. The ending also has like 50 pages worth of shoutout to the bioinformatics community and I know it's because he is also a computational biologist but like :) I mean we really are smart and great aren't we?
Overall an entertaining high level overview of biogerontology that anyone would find interesting!
Our society loves to combat aging with creams, herbs, and supplements. Yet at the end of the day, or more specifically- at the end of a life, we accept that aging is an inevitable process in the steady race to death.
Biogerontologists such as Andrew Steele refuse to accept this reality. No one really “dies of old age.� Rather, people experience an accumulation of cell damage and changes that inhibits the body’s ability to maintain homeostasis, leading to a reduction in immune response against diseases and maladies, which in turn leads to death of the organism.
To Steele, aging is a disease that must be defeated. He presents a fascinating overview of the field of biogerontology in three parts: The history of aging, gerontology, and why we age; the past, current, and future of the fight against aging; how to live longer based on research done so far, and where research and technology will soon meet medicine.
The book itself is well written and organized. Steele is also a bit of a personality, he has a Youtube channel and clearly knows how to present facts in a fun and interesting way. The ending also has like 50 pages worth of shoutout to the bioinformatics community and I know it's because he is also a computational biologist but like :) I mean we really are smart and great aren't we?
Some highlights of this book:
- the reference to vampirism and explaining that the media frenzy following a trial suggesting young blood heals old blood was over-represented
- all the times he was personally offended by evolution. ie in regards to antagonistic pleiotrophy: ”So deadly is the spectre of cancer to multicellular organisms that evolution is prepared to put us at risk of disease and deterioration in old age just to be sure we won’t get cancer in youth.�
- how many times he managed to slip in that we need to stop getting fucking suntans. Cells in [sun exposed skin] can accrue ten times as many mutations per year� skin researchers nearly equate skin aging with sun exposure. How much ultraviolet light a patch of skin has received in its lifetime is a significant predictor of how biologically old it is.
you got me w that one babe
-eunuchs
- “we don’t know for sure that diet restriction (DR) has a significant positive effect on humans so there’s no reason to go draconian on a low calorie diet / intermittent fasting. Like there’s a LOT of reason to suspect it might help but seriously I’m not recommending it or anything. 👁️�
- Get vaccinated x3
- When he told us all to be born a woman
Overall an entertaining high level overview of biogerontology that anyone would find interesting!
May 12, 2021
If you’re considering this book in hopes of finding some magical supplement or salve to add ten years to your life, forget it. The author is a PhD physicist turned computational biologist—a serious scientist. In Ageless, he relates the latest findings about the emergence of a new field called biogerontology. The word is a mouthful, but its meaning is transparent: it’s the study of the biological basis of aging and age-related diseases. And the author, Dr. Andrew Steele, contends that advances in the field hold out hope that in the foreseeable future a combination of drugs and genetic engineering can extend both the human lifespan and our healthspan.
In other words, as the subtitle of Steele’s book suggests, we are on the cusp of learning how to get older “without getting old”—staying healthy and active to the end. For me at age eighty, that’s a mighty attractive proposition. It’s hard to resist the prospect of living longer, so long as I’m not bedridden or witless during the additional years.
A paradigm shift in the science of aging
Steele argues that scientists are now beginning to address the phenomenon of aging itself rather than just the signature diseases and infirmities that are associated with it. It’s a paradigm shift, and if the scientists he promotes in this book receive the funding they need to move ahead aggressively, their efforts might make it possible for today’s average global lifespan of 72.6 years—already nearly 10 years higher in the world’s richest countries—to extend to 100 by the end of the century. Not by curing cancer or heart disease, or squelching every pandemic disease to come down the pike, but by manipulating the mechanisms that determine our biological age.
For example, the author asserts, “rather than going after hundreds of types of cancer and finding bespoke treatments for each, we could try to deal with the DNA damage which underlies them all, the senescent cells and chronic inflammation which aggravate them all and the faltering immune defenses which they must all slip past, and reduce the odds of getting cancer in the first place.� He adds much later, “given how far we’ve come in the last 50 years, it would be foolish to bet that the kind of systems biology we’d need to cure aging won’t be possible in the next 50.� Living longer, he suggests, is in our future.
Complex science made simple. Sort of. Sometimes.
For the average person, the science of aging is unfathomably complex. Steele makes it easy to understand—up to a point—but only so long as you have rudimentary knowledge of biology. As the son and brother of doctors, and the husband of a biologist, I’ve picked up a little of that. But I still found myself alternately befuddled or feeling my eyes glaze over as I read Steele’s detailed accounts of how some particular drug or gene acted to extend or truncate the life of mice in laboratory studies. Nonetheless, I found Ageless to be illuminating.
“What’s astounding,� Steele writes, “is that the doubling of human life expectancy since the start of the 1800s has been achieved without any treatments for aging. We’ve scored some indirect hits—improved diets, exercise, cutting out smoking, and preventative medicines to reduce cholesterol or blood pressure all arguably slow parts of the aging process to some extent—but there’s not a single drug or treatment available in your local pharmacy or hospital expressly designed to slow or reverse aging.� Yet, there is every prospect that that will change in the years ahead. Continuing advances in biomedicine will make living longer likely.
Living longer through science
Steele makes clear that “aging isn’t one single thing—but nor is it thousands. We now known enough to attempt to place aging-related changes into categories. Most excitingly, there are few enough that we can hope not only to explain what drives the aging process, but potentially come up with treatments to address it.� Other scientists have proposed grouping those changes into seven or nine categories. Steele describes ten “hallmarks� of the aging process, because “given that aging is a multifaceted process, treating it is going to require a portfolio approach.� As a result, “there may well be dozens of treatments in our eventual repertoire.�
DNA damage and mutations
Trimmed telomeres
Autophagy, amyloids, and adducts
Epigenetic alterations
Accumulation of senescent cells
Malfunctioning mitochondria
Signal failure
Changes in the microbiome
Cellular exhaustion
Malfunction of the immune system
If you understand all the language in this ten-item typology, you’re way ahead of me. Individually, Steele makes each of these terms (more or less) understandable in Ageless. But the experiments he describes to explore how to counter them, and the treatments he proposes, are much harder to grasp. Suffice it to say that the science seems credible. In other words, I’ll take his word for it.
Keep in mind that this is not science fiction. Steele reports on human trials underway on drugs developed to counter several of the items in his list. Subjects, both lab animals and, in a few cases, people, are already living longer as a result. And other scientists are deploying gene therapy, especially now with the benefit of CRISPR-Cas9, to address others.
Three parts to the book
Ageless consists of three parts. In Part 1, Steele describes “An Age-Old Problem,� noting the marked increase in life expectancy we’ve experienced in recent centuries. Part II, based on the typology above, is about “Treating Aging.� In Part 3, he advances his prescription for “Living Longer.� And that last part is the most disappointing. I surely don’t need to be told again not to smoke, drink to excess, overeat, or fail to exercise. He mentions the promise inherent in “probiotics, prebiotics and synbiotics,� all of which are available in certain foods and food supplements. However, he cautions against the use of food supplements in general, many of which he insists cause more harm than good, while the others are of no use at all. Given what I’ve learned from doctors and nutritionists, I believe he does too far with that claim. And vitamin manufacturers will not be happy.
Although Steele is more informative than I’m suggesting here, “Living Longer� was less rewarding for me. It is, in part, an activist’s plea for the governments of rich nations to fund anti-aging research. “Aging causes 85 percent of deaths in the U.S., but receives 6 percent of health research funding,� he notes. But I’m not the right audience for that message.
About the author
Andrew Steele‘s bio on Amazon reads in part: “Dr Andrew Steele is a scientist, writer and campaigner [British for “activist”] based in London. After a PhD in physics from the University of Oxford, Andrew decided that ageing was the single most important scientific challenge of our time, and switched fields to computational biology. He worked at the Francis Crick Institute, using machine learning to decode our DNA and predict heart attacks using patients� NHS medical records. He is now a full-time science writer and presenter.�
In other words, as the subtitle of Steele’s book suggests, we are on the cusp of learning how to get older “without getting old”—staying healthy and active to the end. For me at age eighty, that’s a mighty attractive proposition. It’s hard to resist the prospect of living longer, so long as I’m not bedridden or witless during the additional years.
A paradigm shift in the science of aging
Steele argues that scientists are now beginning to address the phenomenon of aging itself rather than just the signature diseases and infirmities that are associated with it. It’s a paradigm shift, and if the scientists he promotes in this book receive the funding they need to move ahead aggressively, their efforts might make it possible for today’s average global lifespan of 72.6 years—already nearly 10 years higher in the world’s richest countries—to extend to 100 by the end of the century. Not by curing cancer or heart disease, or squelching every pandemic disease to come down the pike, but by manipulating the mechanisms that determine our biological age.
For example, the author asserts, “rather than going after hundreds of types of cancer and finding bespoke treatments for each, we could try to deal with the DNA damage which underlies them all, the senescent cells and chronic inflammation which aggravate them all and the faltering immune defenses which they must all slip past, and reduce the odds of getting cancer in the first place.� He adds much later, “given how far we’ve come in the last 50 years, it would be foolish to bet that the kind of systems biology we’d need to cure aging won’t be possible in the next 50.� Living longer, he suggests, is in our future.
Complex science made simple. Sort of. Sometimes.
For the average person, the science of aging is unfathomably complex. Steele makes it easy to understand—up to a point—but only so long as you have rudimentary knowledge of biology. As the son and brother of doctors, and the husband of a biologist, I’ve picked up a little of that. But I still found myself alternately befuddled or feeling my eyes glaze over as I read Steele’s detailed accounts of how some particular drug or gene acted to extend or truncate the life of mice in laboratory studies. Nonetheless, I found Ageless to be illuminating.
“What’s astounding,� Steele writes, “is that the doubling of human life expectancy since the start of the 1800s has been achieved without any treatments for aging. We’ve scored some indirect hits—improved diets, exercise, cutting out smoking, and preventative medicines to reduce cholesterol or blood pressure all arguably slow parts of the aging process to some extent—but there’s not a single drug or treatment available in your local pharmacy or hospital expressly designed to slow or reverse aging.� Yet, there is every prospect that that will change in the years ahead. Continuing advances in biomedicine will make living longer likely.
Living longer through science
Steele makes clear that “aging isn’t one single thing—but nor is it thousands. We now known enough to attempt to place aging-related changes into categories. Most excitingly, there are few enough that we can hope not only to explain what drives the aging process, but potentially come up with treatments to address it.� Other scientists have proposed grouping those changes into seven or nine categories. Steele describes ten “hallmarks� of the aging process, because “given that aging is a multifaceted process, treating it is going to require a portfolio approach.� As a result, “there may well be dozens of treatments in our eventual repertoire.�
DNA damage and mutations
Trimmed telomeres
Autophagy, amyloids, and adducts
Epigenetic alterations
Accumulation of senescent cells
Malfunctioning mitochondria
Signal failure
Changes in the microbiome
Cellular exhaustion
Malfunction of the immune system
If you understand all the language in this ten-item typology, you’re way ahead of me. Individually, Steele makes each of these terms (more or less) understandable in Ageless. But the experiments he describes to explore how to counter them, and the treatments he proposes, are much harder to grasp. Suffice it to say that the science seems credible. In other words, I’ll take his word for it.
Keep in mind that this is not science fiction. Steele reports on human trials underway on drugs developed to counter several of the items in his list. Subjects, both lab animals and, in a few cases, people, are already living longer as a result. And other scientists are deploying gene therapy, especially now with the benefit of CRISPR-Cas9, to address others.
Three parts to the book
Ageless consists of three parts. In Part 1, Steele describes “An Age-Old Problem,� noting the marked increase in life expectancy we’ve experienced in recent centuries. Part II, based on the typology above, is about “Treating Aging.� In Part 3, he advances his prescription for “Living Longer.� And that last part is the most disappointing. I surely don’t need to be told again not to smoke, drink to excess, overeat, or fail to exercise. He mentions the promise inherent in “probiotics, prebiotics and synbiotics,� all of which are available in certain foods and food supplements. However, he cautions against the use of food supplements in general, many of which he insists cause more harm than good, while the others are of no use at all. Given what I’ve learned from doctors and nutritionists, I believe he does too far with that claim. And vitamin manufacturers will not be happy.
Although Steele is more informative than I’m suggesting here, “Living Longer� was less rewarding for me. It is, in part, an activist’s plea for the governments of rich nations to fund anti-aging research. “Aging causes 85 percent of deaths in the U.S., but receives 6 percent of health research funding,� he notes. But I’m not the right audience for that message.
About the author
Andrew Steele‘s bio on Amazon reads in part: “Dr Andrew Steele is a scientist, writer and campaigner [British for “activist”] based in London. After a PhD in physics from the University of Oxford, Andrew decided that ageing was the single most important scientific challenge of our time, and switched fields to computational biology. He worked at the Francis Crick Institute, using machine learning to decode our DNA and predict heart attacks using patients� NHS medical records. He is now a full-time science writer and presenter.�
February 25, 2021
Disclaimer: I was given an ARC of this book by Doubleday Books via NetGalley in exchange for an honest review.
Over the past two years Longevity, Bio-gerontology, or Life Extension has been a pet subject of mine and during that time I have read over 15 books on different aspects of this topic. With that background I can honestly say that Ageless by Andrew Steele is one of the top books on the subject.
What Ageless does exceptionally well over other books in the topic is being able to convey the sometimes complex biology of aging research in a simple, yet detailed, and more importantly readable and entertaining way. Many books are able to provide detail however they come across as dense and academic so they are not accessible to the standard reader. Others are entertaining but you come away from the book with only a taste of the current situation as only portions of the science are explored. This book strikes the balance between these two positions perfectly.
If you are interested in a no-bs, not overly-optimistic look at the current science of a new emerging field this should be high on your list.
Over the past two years Longevity, Bio-gerontology, or Life Extension has been a pet subject of mine and during that time I have read over 15 books on different aspects of this topic. With that background I can honestly say that Ageless by Andrew Steele is one of the top books on the subject.
What Ageless does exceptionally well over other books in the topic is being able to convey the sometimes complex biology of aging research in a simple, yet detailed, and more importantly readable and entertaining way. Many books are able to provide detail however they come across as dense and academic so they are not accessible to the standard reader. Others are entertaining but you come away from the book with only a taste of the current situation as only portions of the science are explored. This book strikes the balance between these two positions perfectly.
If you are interested in a no-bs, not overly-optimistic look at the current science of a new emerging field this should be high on your list.
March 1, 2023
Pentru că am citit-o după Meduza fără vârstă (pe același subiect) am simțit-o puțin mai complicată. Este foarte interesantă și încărcată de explicații, studii și experimente dar și ușor nerealistă.
Bineînțeles, știința avansează constant dar suntem totuși departe de a ajunge la combaterea procesului de îmbătrânire. Cu fiecare pas făcut spre aflarea soluției miraculoare aflăm ce nu funcționează + alte lucruri care ar putea merge prost.
Ce mi-a plăcut a fost ideea cu care rezonez destul destul de mult și anume că este necesar să acordăm o mai mare importanță întregului proces al îmbătrânirii în loc să acționăm asupra unor boli specifice ce apar exact din cauză că îmbătrânim.
Bineînțeles, știința avansează constant dar suntem totuși departe de a ajunge la combaterea procesului de îmbătrânire. Cu fiecare pas făcut spre aflarea soluției miraculoare aflăm ce nu funcționează + alte lucruri care ar putea merge prost.
Ce mi-a plăcut a fost ideea cu care rezonez destul destul de mult și anume că este necesar să acordăm o mai mare importanță întregului proces al îmbătrânirii în loc să acționăm asupra unor boli specifice ce apar exact din cauză că îmbătrânim.
January 30, 2021
I listened to the audiobook of this and recommend it. Andrew Steele's enthusiasm for his topic is infectious, and he's clearly experienced and comfortable at the microphone.
His thesis is fascinating. In brief, 'curing' ageing is a far better bet than spending time trying to cure many of the common diseases of old age such as heart disease, cancer or dementia.
Steele makes a convincing and balanced case. He gives a lot of detail about how our bodies work, how we got to find out how our bodies work, and what debates continue as to the best way to live to healthy old age.
Highly recommended.
His thesis is fascinating. In brief, 'curing' ageing is a far better bet than spending time trying to cure many of the common diseases of old age such as heart disease, cancer or dementia.
Steele makes a convincing and balanced case. He gives a lot of detail about how our bodies work, how we got to find out how our bodies work, and what debates continue as to the best way to live to healthy old age.
Highly recommended.
August 31, 2021
Note that this is primarily NOT a book about how to keep yourself from feeling the effects of ageing, it's about the scientific breakthroughs that are currently being studied that could prevent future generations from ageing. So, still pretty interesting, and the author does a good job breaking down the science for a non scientist like me to read along and not feel hopelessly lost.
February 11, 2022
Liked this book a lot more than the David Sinclair one.
May 23, 2021
The latest book on aging is a bit more ambitious than the that I reviewed, but still rather modest compared to that heralded the start of serious attempts at fighting aging.
Ageless is relatively balanced, well-organized, and comprehensive.
Can Aging be Reversed?
Steele presents many hints that age-related health decline can be slowed, or maybe even reversed:
* the existence of organisms that don't age (i.e. their mortality rate is stable or declines with age): naked mole rats, and many species of fish.
* A number of experiments have shown that small animals can be made to live longer than their maximum natural lifespan.
* the markers of age for individual cells get reset when they become a new embryo.
* cloned animals show the same resetting of cellular age, suggesting that the reset cellular age.
Hallmarks
Steele proposes 10 hallmarks of aging. These are closely related to the on which many researchers seem to be converging.
How confident should we be that fixing those hallmarks will eliminate age-related health declines? I'm disappointed that Steele says little to answer this.
That contrasts with Aubrey de Grey's argument that there are that might need to be fixed in order to cure age-related health decline. Aubrey's main argument for believing they're the only categories that need fixing is that the last one was identified in 1972. If there were more, we'd expect scientists would still be identifying them, especially given the increase in funding for aging research.
One way that might be wrong is that 1972 was about when slowed innovation in the US. A large centralization of funding may have caused a big increase in groupthink and risk aversion, suppressing many kinds of paradigm shifts that might be needed to find other categories of aging damage.
I don't have any clear evidence of increasing groupthink among aging researchers around 1972. I have some evidence of groupthink, but I don't think it has been increasing. So I'll estimate there's maybe a 10% chance that stagnating science is why Aubrey's seven categories look complete.
A more likely reason for Steele to have avoided this argument is that Steele proposes three hallmarks of aging that don't clearly correspond to any of Aubrey's seven categories:
* Microbiome changes seem to have been one of the of aging. We have relatively good theories about how to fix the microbiome, but they're a pain in the ass to evaluate. Aubrey might be guilty of underestimating the importance of microbiome changes, but I'm fairly sure that has few implications for the overall difficulty of fighting aging.
* is hardly news. Aubrey treats it as downstream from other categories of damage. This seems like a fairly minor difference from Steele's treatment.
* changes are a bigger challenge for Aubrey's argument, and might explain why Steele avoids that argument.
Epigenetics seems not to have been proposed as a cause of aging until about . How much should that weaken our confidence that we've identified all the factors that contribute to aging?
Part of Aubrey's lack of interest in epigenetics is because his strategy for solving cancer ought to reverse the important epigenetic changes via supplying new stem cells.
Aubrey seems reluctant to classify epigenetic changes as damage. Maybe epigenetic changes are just symptoms of other kinds of damage, in which case Aubrey's view will turn out to work fairly well.
But I see signs that epigenetic changes are programmed causes of aging, and that they qualify as a new category that weakens his claim that the last new category was found in 1972. Aubrey seems to be betting on a fairly pure model of aging as damage, and epigenetic changes as causes of aging don't fit that paradigm very well. I prefer to weakly bet that some aging is programmed via epigenetic changes. So I'm glad that Steele hedges his bets on this subject.
My best guess is that if epigenetic changes are an important cause of aging, then progress will be a good deal easier than most experts predict.
Cancer
Cancer seems like it will be the hardest part of aging to solve.
Aubrey's proposed cancer cure is a bit scary, since it would make patients dependent on getting new stem cell treatments every decade or so. That's less scary than normal aging, but I want a good deal of research into other options.
Fortunately, Steele provides several ideas about treating cancer that are new to me, sound vaguely promising, and don't appear to have unusual risks.
I've been intending, for the past two years, to take a deep dive (any month now) into cancer research, in order to better evaluate what I can do about my personal risk of cancer. A small part of my procrastination was due to not knowing where to start. Steele's discussion provides some good starting points.
* We might increase expression of the , combined with more telomerase. This might be how large animals such as elephants avoid the high cancer rate that theory says they should have (Peto's Paradox)
* We might detect, and maybe treat, cancer at a much earlier stage (maybe when it's just a millimeter in diameter).
* mutations appear to play an important role in cancer, while also creating important cardiovascular and diabetes risks. It's unclear how this gets translated to treatments, but it presents an interesting target.
None of these individually are enough to get my hopes up much, and they seem to be further than I'd like from being safe treatments, but the variety of strategies is somewhat reassuring.
Why Now?
Research into doing something about aging didn't start taking off until the 1990s.
Steele claims that was influenced by when proof became available that aging could be tractably altered in the lab in "scientifically interesting" ways.
Yet on calorie restriction in rats didn't generate interest in aging research.
There was a tiny reaction to Friedman and Johnson's showing that a single mutation could slow C. elegans aging by 50%.
The trigger that, according to Steele, set off a clear movement toward aging research was 1993 discovery of another mutation that doubled C. elegans lifespan. That may have been the main advance inspired by the 1988 paper.
Unlike the first two discoveries, this one showed no trade-off between longer life and fertility. So it became hard to claim that natural aging was near-optimal for C. elegans.
That's presumably part of how aging research became respectable, but it feels incomplete.
I suspect part of the timing was due to running low on other low-hanging fruit.
Up until the 1960s, fighting infectious disease was a more tractable way to save lives. After that, we had the , which sure looked more winnable than a war on aging, back when the war was declared.
By the time aging research started its growth, the war on cancer had lost nearly all of its youthful vigor. The other leading deadly diseases looked almost as hard to tackle. As researchers became pessimistic about quick progress, it became harder to find research that was more promising than aging research.
Practical Advice
What can an ordinary person do now to live longer? Steele gives a mostly standard and unsurprising list of recommendations, which look about 85% correct. His top priorities are mostly things we all know we should do: exercise, eat more fruits and vegetables, brush our teeth, etc.
I got suspicious at the 7th entry in his list: wear sunscreen. I expect that will help people whose sun exposure is erratic. But I suspect the optimal advice is to, instead, get regular enough sun exposure to avoid the risk of sunburn. When combined with his advice to avoid supplements, sunscreen is likely to cause vitamin D deficiency. It's hard to rule out other benefits of sunlight that might be impaired by sunscreen.
Another risk is that most sunscreens get absorbed into the body, and there's some that they disrupt sex hormones.
Root Causes of Aging
Steele provides a fairly standard explanation of the mainstream expert consensus, as it was several decades ago, on why aging evolved:
* which is likely to be at least part of what's going on.
* used to be a leading hypothesis. Steele treats it seriously. It looks pretty unlikely to me, due to evidence that aging is promoted by genes that are conserved across a wide variety of species.
* the clearly has some truth to it. Evolution does make some trade-offs between investing in reproduction versus in the health of adults. But there's enough contrary evidence that it's hard to consider this the main cause of aging (e.g. from experiments that increase lifespan at no apparent cost).
Steele rejects the idea that aging is programmed, treating it as if experts stopped taking it seriously long ago.
The earliest arguments for programmed aging were faulty enough that they don't deserve to be taken seriously. Yet a recent survey () suggests that about 40% of experts believe aging is programmed.
In other parts of the book, Steele describes features that seem fairly clock-like: telomeres, the programmed decline in thymus, and epigenetic clocks. When discussing these topics, he seems not to care whether he's hinting at programmed clocks.
For each of these clock-like features, it's not too hard to imagine explanations based on antagonistic pleiotropy or disposable soma. But that takes some effort, especially for the epigenetic clock, if we take seriously, as Steele does, the idea that those features might cause aging, rather than being just symptoms.
What about species that die too suddenly after reproducing for the death to look accidental (e.g. salmon)? Kin selection is at least for programmed aging there. That's probably of limited relevance to human aging, but it's hard to fully rule out that possibility that some of our very distant ancestors evolved programmed aging, and that more recent selection pressures have not yet been sufficient to fully remove those effects.
Maybe Steele intended to dismiss only the crappy arguments for programmed aging that were somewhat popular a generation ago? It's odd that Steele's knowledge sounds firmly stuck in the 20th century when discussing the evolution of aging, but sounds quite up to date in the rest of the book.
Conclusion
Ageless is currently my top recommendation for a book on aging, although at the rate new books are being published on the topic, that recommendation is likely to age quickly.
It's the most mainstream book I've seen on this subject. That's a bit too mainstream for an optimal picture of aging research. But you shouldn't expect a single book to provide an optimal picture in a field as immature as this.
Ageless is relatively balanced, well-organized, and comprehensive.
Can Aging be Reversed?
Steele presents many hints that age-related health decline can be slowed, or maybe even reversed:
* the existence of organisms that don't age (i.e. their mortality rate is stable or declines with age): naked mole rats, and many species of fish.
* A number of experiments have shown that small animals can be made to live longer than their maximum natural lifespan.
* the markers of age for individual cells get reset when they become a new embryo.
* cloned animals show the same resetting of cellular age, suggesting that the reset cellular age.
Hallmarks
Steele proposes 10 hallmarks of aging. These are closely related to the on which many researchers seem to be converging.
How confident should we be that fixing those hallmarks will eliminate age-related health declines? I'm disappointed that Steele says little to answer this.
That contrasts with Aubrey de Grey's argument that there are that might need to be fixed in order to cure age-related health decline. Aubrey's main argument for believing they're the only categories that need fixing is that the last one was identified in 1972. If there were more, we'd expect scientists would still be identifying them, especially given the increase in funding for aging research.
One way that might be wrong is that 1972 was about when slowed innovation in the US. A large centralization of funding may have caused a big increase in groupthink and risk aversion, suppressing many kinds of paradigm shifts that might be needed to find other categories of aging damage.
I don't have any clear evidence of increasing groupthink among aging researchers around 1972. I have some evidence of groupthink, but I don't think it has been increasing. So I'll estimate there's maybe a 10% chance that stagnating science is why Aubrey's seven categories look complete.
A more likely reason for Steele to have avoided this argument is that Steele proposes three hallmarks of aging that don't clearly correspond to any of Aubrey's seven categories:
* Microbiome changes seem to have been one of the of aging. We have relatively good theories about how to fix the microbiome, but they're a pain in the ass to evaluate. Aubrey might be guilty of underestimating the importance of microbiome changes, but I'm fairly sure that has few implications for the overall difficulty of fighting aging.
* is hardly news. Aubrey treats it as downstream from other categories of damage. This seems like a fairly minor difference from Steele's treatment.
* changes are a bigger challenge for Aubrey's argument, and might explain why Steele avoids that argument.
Epigenetics seems not to have been proposed as a cause of aging until about . How much should that weaken our confidence that we've identified all the factors that contribute to aging?
Part of Aubrey's lack of interest in epigenetics is because his strategy for solving cancer ought to reverse the important epigenetic changes via supplying new stem cells.
Aubrey seems reluctant to classify epigenetic changes as damage. Maybe epigenetic changes are just symptoms of other kinds of damage, in which case Aubrey's view will turn out to work fairly well.
But I see signs that epigenetic changes are programmed causes of aging, and that they qualify as a new category that weakens his claim that the last new category was found in 1972. Aubrey seems to be betting on a fairly pure model of aging as damage, and epigenetic changes as causes of aging don't fit that paradigm very well. I prefer to weakly bet that some aging is programmed via epigenetic changes. So I'm glad that Steele hedges his bets on this subject.
My best guess is that if epigenetic changes are an important cause of aging, then progress will be a good deal easier than most experts predict.
Cancer
Cancer seems like it will be the hardest part of aging to solve.
Aubrey's proposed cancer cure is a bit scary, since it would make patients dependent on getting new stem cell treatments every decade or so. That's less scary than normal aging, but I want a good deal of research into other options.
Fortunately, Steele provides several ideas about treating cancer that are new to me, sound vaguely promising, and don't appear to have unusual risks.
I've been intending, for the past two years, to take a deep dive (any month now) into cancer research, in order to better evaluate what I can do about my personal risk of cancer. A small part of my procrastination was due to not knowing where to start. Steele's discussion provides some good starting points.
* We might increase expression of the , combined with more telomerase. This might be how large animals such as elephants avoid the high cancer rate that theory says they should have (Peto's Paradox)
* We might detect, and maybe treat, cancer at a much earlier stage (maybe when it's just a millimeter in diameter).
* mutations appear to play an important role in cancer, while also creating important cardiovascular and diabetes risks. It's unclear how this gets translated to treatments, but it presents an interesting target.
None of these individually are enough to get my hopes up much, and they seem to be further than I'd like from being safe treatments, but the variety of strategies is somewhat reassuring.
Why Now?
Research into doing something about aging didn't start taking off until the 1990s.
Steele claims that was influenced by when proof became available that aging could be tractably altered in the lab in "scientifically interesting" ways.
Yet on calorie restriction in rats didn't generate interest in aging research.
There was a tiny reaction to Friedman and Johnson's showing that a single mutation could slow C. elegans aging by 50%.
The trigger that, according to Steele, set off a clear movement toward aging research was 1993 discovery of another mutation that doubled C. elegans lifespan. That may have been the main advance inspired by the 1988 paper.
Unlike the first two discoveries, this one showed no trade-off between longer life and fertility. So it became hard to claim that natural aging was near-optimal for C. elegans.
That's presumably part of how aging research became respectable, but it feels incomplete.
I suspect part of the timing was due to running low on other low-hanging fruit.
Up until the 1960s, fighting infectious disease was a more tractable way to save lives. After that, we had the , which sure looked more winnable than a war on aging, back when the war was declared.
By the time aging research started its growth, the war on cancer had lost nearly all of its youthful vigor. The other leading deadly diseases looked almost as hard to tackle. As researchers became pessimistic about quick progress, it became harder to find research that was more promising than aging research.
Practical Advice
What can an ordinary person do now to live longer? Steele gives a mostly standard and unsurprising list of recommendations, which look about 85% correct. His top priorities are mostly things we all know we should do: exercise, eat more fruits and vegetables, brush our teeth, etc.
I got suspicious at the 7th entry in his list: wear sunscreen. I expect that will help people whose sun exposure is erratic. But I suspect the optimal advice is to, instead, get regular enough sun exposure to avoid the risk of sunburn. When combined with his advice to avoid supplements, sunscreen is likely to cause vitamin D deficiency. It's hard to rule out other benefits of sunlight that might be impaired by sunscreen.
Another risk is that most sunscreens get absorbed into the body, and there's some that they disrupt sex hormones.
Root Causes of Aging
Steele provides a fairly standard explanation of the mainstream expert consensus, as it was several decades ago, on why aging evolved:
* which is likely to be at least part of what's going on.
* used to be a leading hypothesis. Steele treats it seriously. It looks pretty unlikely to me, due to evidence that aging is promoted by genes that are conserved across a wide variety of species.
* the clearly has some truth to it. Evolution does make some trade-offs between investing in reproduction versus in the health of adults. But there's enough contrary evidence that it's hard to consider this the main cause of aging (e.g. from experiments that increase lifespan at no apparent cost).
Steele rejects the idea that aging is programmed, treating it as if experts stopped taking it seriously long ago.
We now know that we don't all have some ticking, internal clock, programmed to kill parents to make space for their children.
The earliest arguments for programmed aging were faulty enough that they don't deserve to be taken seriously. Yet a recent survey () suggests that about 40% of experts believe aging is programmed.
In other parts of the book, Steele describes features that seem fairly clock-like: telomeres, the programmed decline in thymus, and epigenetic clocks. When discussing these topics, he seems not to care whether he's hinting at programmed clocks.
For each of these clock-like features, it's not too hard to imagine explanations based on antagonistic pleiotropy or disposable soma. But that takes some effort, especially for the epigenetic clock, if we take seriously, as Steele does, the idea that those features might cause aging, rather than being just symptoms.
What about species that die too suddenly after reproducing for the death to look accidental (e.g. salmon)? Kin selection is at least for programmed aging there. That's probably of limited relevance to human aging, but it's hard to fully rule out that possibility that some of our very distant ancestors evolved programmed aging, and that more recent selection pressures have not yet been sufficient to fully remove those effects.
Maybe Steele intended to dismiss only the crappy arguments for programmed aging that were somewhat popular a generation ago? It's odd that Steele's knowledge sounds firmly stuck in the 20th century when discussing the evolution of aging, but sounds quite up to date in the rest of the book.
Conclusion
Ageless is currently my top recommendation for a book on aging, although at the rate new books are being published on the topic, that recommendation is likely to age quickly.
It's the most mainstream book I've seen on this subject. That's a bit too mainstream for an optimal picture of aging research. But you shouldn't expect a single book to provide an optimal picture in a field as immature as this.
November 1, 2022
Absolutely despised this book. Thought it would be interesting and useful information, but he skipped most of the ethics and went straight to wishful thinking unfortunately.
Honestly, most of this stuff is not that complicated. I don't know why it took him 350 pages to introduce homeostasis or why he struggled so hard with sentence structure. I imagine his inner monologue while writing was: "Oh yes, swapping to acronyms immediately after introducing a term for the first time will make this book easier to understand", "I am going to tell these people that they could lose a few pounds", "This technique is mostly unsupported with negative side effects? It won't be if we spend a lot of time and money on it".
His style of writing (obnoxious and condescending) is not aberrant (Andrew's favourite word) for scientists. Super all over the place with little in the way of segues or like... full stops. I would say he also just comes off as annoying. Also: another male author solving sexism by using she/her default pronouns 2-3 times. Congrats on the feminism Andrew!
(and just as a thought on the central premise - I would in fact create ageing to solve socioeconomic issues in a world of immortality)
Honestly, most of this stuff is not that complicated. I don't know why it took him 350 pages to introduce homeostasis or why he struggled so hard with sentence structure. I imagine his inner monologue while writing was: "Oh yes, swapping to acronyms immediately after introducing a term for the first time will make this book easier to understand", "I am going to tell these people that they could lose a few pounds", "This technique is mostly unsupported with negative side effects? It won't be if we spend a lot of time and money on it".
His style of writing (obnoxious and condescending) is not aberrant (Andrew's favourite word) for scientists. Super all over the place with little in the way of segues or like... full stops. I would say he also just comes off as annoying. Also: another male author solving sexism by using she/her default pronouns 2-3 times. Congrats on the feminism Andrew!
(and just as a thought on the central premise - I would in fact create ageing to solve socioeconomic issues in a world of immortality)
February 3, 2021
I have mixed feelings on this one. The author seems very excited about telomeres, and senescent cells and epigenetics. Okay, fair enough, but he has a very biased viewpoint about anti-ageing research that really troubled me. It troubles me that this scientist has such tunnel vision about the potential of these treatments, particularly in the hands of rich and powerful people. While individual human lifespans are lengthening, there is this other little thing called climate change. As it is, we are facing widespread disease and destruction due to loss of habitat, the spread of disease, natural disasters and their fallout... so many challenges that we know are directly caused by having too many people on this planet. I was really frustrated by the lack of balance in the book.
There was some pretty interesting research, but maybe there’s a part of me that actually hopes that we never find a “cure� for ageing. I wonder if we should let nature take its course. Science has brought many breakthroughs for humans and we are getting better and better at surviving, but we do it through dominating the land and destroying it.
There was some pretty interesting research, but maybe there’s a part of me that actually hopes that we never find a “cure� for ageing. I wonder if we should let nature take its course. Science has brought many breakthroughs for humans and we are getting better and better at surviving, but we do it through dominating the land and destroying it.
July 25, 2024
“Ageless: The New Science of Getting Older Without Getting Old� by Andrew Steele is a fascinating exploration into the science of aging and the potential for extending human lifespan. Narrated by the author himself, the audiobook offers a compelling and accessible journey through the latest research in the field of gerontology.
** Engaging Narration
Andrew Steele's narration adds a personal touch to the audiobook. His clear and enthusiastic delivery makes complex scientific concepts more digestible for the average listener. Steele's background as a computational biologist shines through as he explains intricate details with clarity and passion. His ability to break down complicated topics into understandable segments is one of the audiobook's strongest points.
** Comprehensive Exploration of Aging
The book delves into the biological mechanisms of aging, discussing topics such as DNA damage, mitochondrial dysfunction, and the role of telomeres. Steele provides a thorough overview of the hallmarks of aging, making it clear why our bodies deteriorate over time. He also explores the evolutionary reasons behind aging, offering insights into why certain species, like tortoises, exhibit negligible senescence.
** Cutting-Edge Research
One of the most exciting aspects of "Ageless" is its focus on cutting-edge research aimed at combating aging. Steele takes listeners inside laboratories where scientists are developing therapies to slow down or even reverse the aging process. From senolytics, which target and remove senescent cells, to gene editing techniques like CRISPR, the audiobook covers a wide range of innovative approaches. Steele's optimism about the future of anti-aging research is infectious, leaving listeners hopeful about the possibilities.
** Practical Advice
While much of the book is dedicated to scientific research, Steele also offers practical advice for those looking to extend their healthy years. He emphasizes the importance of lifestyle choices such as regular exercise, a balanced diet, and avoiding smoking. Interestingly, Steele advises against relying on supplements and longevity drugs, at least for now, as the science behind them is not yet conclusive.
** Ethical Considerations
Steele does not shy away from discussing the ethical implications of life extension. He raises important questions about the societal impact of significantly longer lifespans, such as the potential strain on resources and the ethical considerations of who gets access to these treatments. This balanced approach ensures that the audiobook is not just a scientific exploration but also a thoughtful consideration of the broader implications of anti-aging research.
** Personal Reflections
Throughout the audiobook, Steele shares personal anecdotes and reflections, making the content more relatable. His journey from a physicist to a computational biologist interested in aging adds a personal dimension to the narrative. These moments of introspection help to humanize the science, making it more engaging for listeners.
** Criticisms
While "Ageless" is a comprehensive and engaging audiobook, it is not without its criticisms. Some listeners might find the scientific details overwhelming, especially if they are not familiar with the field of biology. Additionally, the book's optimistic tone might come across as overly idealistic to some, particularly given the current limitations of anti-aging research.
** Conclusion
In conclusion, "Ageless" by Andrew Steele is a thought-provoking and informative audiobook that offers a deep dive into the science of aging. Steele's engaging narration, combined with his ability to explain complex scientific concepts, makes this audiobook a must-listen for anyone interested in the future of aging and longevity. While it may be dense at times, the wealth of information and the hopeful outlook it provides make it a valuable resource for understanding the potential of anti-aging research.
** Engaging Narration
Andrew Steele's narration adds a personal touch to the audiobook. His clear and enthusiastic delivery makes complex scientific concepts more digestible for the average listener. Steele's background as a computational biologist shines through as he explains intricate details with clarity and passion. His ability to break down complicated topics into understandable segments is one of the audiobook's strongest points.
** Comprehensive Exploration of Aging
The book delves into the biological mechanisms of aging, discussing topics such as DNA damage, mitochondrial dysfunction, and the role of telomeres. Steele provides a thorough overview of the hallmarks of aging, making it clear why our bodies deteriorate over time. He also explores the evolutionary reasons behind aging, offering insights into why certain species, like tortoises, exhibit negligible senescence.
** Cutting-Edge Research
One of the most exciting aspects of "Ageless" is its focus on cutting-edge research aimed at combating aging. Steele takes listeners inside laboratories where scientists are developing therapies to slow down or even reverse the aging process. From senolytics, which target and remove senescent cells, to gene editing techniques like CRISPR, the audiobook covers a wide range of innovative approaches. Steele's optimism about the future of anti-aging research is infectious, leaving listeners hopeful about the possibilities.
** Practical Advice
While much of the book is dedicated to scientific research, Steele also offers practical advice for those looking to extend their healthy years. He emphasizes the importance of lifestyle choices such as regular exercise, a balanced diet, and avoiding smoking. Interestingly, Steele advises against relying on supplements and longevity drugs, at least for now, as the science behind them is not yet conclusive.
** Ethical Considerations
Steele does not shy away from discussing the ethical implications of life extension. He raises important questions about the societal impact of significantly longer lifespans, such as the potential strain on resources and the ethical considerations of who gets access to these treatments. This balanced approach ensures that the audiobook is not just a scientific exploration but also a thoughtful consideration of the broader implications of anti-aging research.
** Personal Reflections
Throughout the audiobook, Steele shares personal anecdotes and reflections, making the content more relatable. His journey from a physicist to a computational biologist interested in aging adds a personal dimension to the narrative. These moments of introspection help to humanize the science, making it more engaging for listeners.
** Criticisms
While "Ageless" is a comprehensive and engaging audiobook, it is not without its criticisms. Some listeners might find the scientific details overwhelming, especially if they are not familiar with the field of biology. Additionally, the book's optimistic tone might come across as overly idealistic to some, particularly given the current limitations of anti-aging research.
** Conclusion
In conclusion, "Ageless" by Andrew Steele is a thought-provoking and informative audiobook that offers a deep dive into the science of aging. Steele's engaging narration, combined with his ability to explain complex scientific concepts, makes this audiobook a must-listen for anyone interested in the future of aging and longevity. While it may be dense at times, the wealth of information and the hopeful outlook it provides make it a valuable resource for understanding the potential of anti-aging research.
June 5, 2022
Hmmm� I-am dat 3 stele pentru ca m-as simti prost sa dau mai putin unei carti de la editura Publica, din sfera aceasta de sanatate, dezvoltare personala. Defapt nu m-as simti prost absolut deloc insa, sa zicem ca aceasta e de 3. O carte luuuunga, presarata pe alocuri cu informatii interesante, INSA, pentru mine, care totusi am studii superioare in domeniul medical este greoaie, cu prea multe detalii despre genetica, celule, diverse structuri, markeri care personal nu ma interesau. Nu-mi inchipui cum ar fi pentru cineva care nu are habar de sfera asta medicala. M-a tinut pe loc cartea asta, a fost interesant la nivel de cultura generala dar m-a plictisit. Credeam ca o sa fie mai mult despre sfaturi practice de pus acum in practica pentru tot omul de rand dar e mai mult despre stiinta numita gerontologie si cum se poate dezvolta aceasta in viitor si care sunt procesele ce duc la imbatranire si ce tratamente sunt in curs de avizare/descoperire. Abia de la pagina 341 incepe un limbaj cat de cat uman cu sfaturi de aplicat dar si astea banale, pe care cu siguranta toata lumea le stie.
Am cumparat-o dupa ce am citit cateva pagini pe site la editura Publica ai m-a atras insa a cam fost pierdere de timp.
Am cumparat-o dupa ce am citit cateva pagini pe site la editura Publica ai m-a atras insa a cam fost pierdere de timp.
May 8, 2021
When you're truly interested in something, you end up reading any book you can find on the topic.
.
This book is merely a status update on the research for stopping / reversing aging itself.
.
This book is merely a status update on the research for stopping / reversing aging itself.
April 20, 2021
The book is a bit too scientific for my test.
Too complicated, too difficult to follow
Too complicated, too difficult to follow
March 14, 2025
Много учени, финансирани от много фармацефтични компании се занимават да изучават човешкото (е, повече на белите мишки) стареене - самите процеси на стареене, какво води до тях, как се измерва стареенето и разбира се как да го забавим.
Едни от основните усилия са насочени не точно към удължаване на човешкия живот, а по-скоро към удължаване на младия и здрав живот: т.е. може пак да живееш до 80 (което е средната продължителност на живота в развития свят в момента), но поне да си жизнен и да се чувстваш добре почти до края.
Книгата е написана на разбираем език, но описва доста добре основните неща, с които гореописаните учени се занимават.
Частта със съвети как да приложим най-новите достижения на медицината в областта, за да удължим живота и младостта си обаче са толкова прости и всеобщо известни, че чак разочароващи. Докато в книгата авторът говори за неща като генни терапии, вливане на стволови клетки, удължаване на теломери, съветите му за добро здраве са (не се шегувам, буквално цитирам):
1. Не пуши
2. Не бъди дебел
3. Спортувай
4. Спи достатъчно
5. Бъди жена (това е леко шега, на базата на факта, че жените средностатистически живеят по-дълго по различни причини, някои от тях неизвестни).
Всичко останало, според автора, са нови методи, които имат нужда от още проучване, преди да може със сигурност да се каже, че помагат - нещо което му прави голяма чест, за разлика от Дейвид Синклер, който дава една купчина съвети, базирани на мъгляви резултати от експерименти с мишки и растежа на маята.
И макар Сиклер да уцелва (според мен) два от основните и важни методи - лечебно гладуване и излагане на студ, той е надраскал и един куп глупости заедно с тях. Андрю Стийл за мен печели надпреварата между двамата заради научната си скромност и, четимостта на книгата.
Едни от основните усилия са насочени не точно към удължаване на човешкия живот, а по-скоро към удължаване на младия и здрав живот: т.е. може пак да живееш до 80 (което е средната продължителност на живота в развития свят в момента), но поне да си жизнен и да се чувстваш добре почти до края.
Книгата е написана на разбираем език, но описва доста добре основните неща, с които гореописаните учени се занимават.
Частта със съвети как да приложим най-новите достижения на медицината в областта, за да удължим живота и младостта си обаче са толкова прости и всеобщо известни, че чак разочароващи. Докато в книгата авторът говори за неща като генни терапии, вливане на стволови клетки, удължаване на теломери, съветите му за добро здраве са (не се шегувам, буквално цитирам):
1. Не пуши
2. Не бъди дебел
3. Спортувай
4. Спи достатъчно
5. Бъди жена (това е леко шега, на базата на факта, че жените средностатистически живеят по-дълго по различни причини, някои от тях неизвестни).
Всичко останало, според автора, са нови методи, които имат нужда от още проучване, преди да може със сигурност да се каже, че помагат - нещо което му прави голяма чест, за разлика от Дейвид Синклер, който дава една купчина съвети, базирани на мъгляви резултати от експерименти с мишки и растежа на маята.
И макар Сиклер да уцелва (според мен) два от основните и важни методи - лечебно гладуване и излагане на студ, той е надраскал и един куп глупости заедно с тях. Андрю Стийл за мен печели надпреварата между двамата заради научната си скромност и, четимостта на книгата.
September 17, 2021
This was a fascinating read. I very much enjoyed the structure here - starting with explanation of the ideology behind the science of aging, explaining the current situation, the past, future projections and pros&cons, then moving on to the actual science, current research and future possibilities.
Being honest, the science went over my head in places and I'm not too proud to admit it. This book is definitely not wishy-washy and it deals in hard science, so I wouldn't mind recommending it even to healthcare professionals and medical researchers. It has a holistic approach and could especially benefit to people with narrower focus.
My conclusion is - unless you are planning to die before you turn 40, this book is very much worth reading and paying attention to. Even if you don't have a medical background or higher education good enough to follow the detailed science later on, going at least through the beginning (perhaps the first 20%) can open your eyes in so many ways....I heartily recommend it :)
Being honest, the science went over my head in places and I'm not too proud to admit it. This book is definitely not wishy-washy and it deals in hard science, so I wouldn't mind recommending it even to healthcare professionals and medical researchers. It has a holistic approach and could especially benefit to people with narrower focus.
My conclusion is - unless you are planning to die before you turn 40, this book is very much worth reading and paying attention to. Even if you don't have a medical background or higher education good enough to follow the detailed science later on, going at least through the beginning (perhaps the first 20%) can open your eyes in so many ways....I heartily recommend it :)
December 17, 2021
Although I gave this book a five-star rating, I have somewhat mixed feelings about it. First, the writing is excellent, at least in the chapters I understood. The problem for me was that the first two parts of the book were pretty technical. I have a degree in physics but you almost need a degree in chemistry and biology to follow some of the narrative. I'm getting older and I tend to like books that are easy to read. But, the final two chapters made the book worth the price. In the next to last chapter he lists eleven things we can do to live longer. Most of these we know (exercise, eat right, get enough sleep, etc.) But for me the real reward was in the final chapter where he writes about metformin, a drug that is used to treat diabetes. Research has shown that the drug may also reduce the risk of cancer and dementia and extend lifespan by a bit. I'm going to call my doctor tomorrow to see if she'll prescribe it!
April 23, 2021
Please do not read this book if you are looking for lifestyle or even bio-hacking ways to live longer and healthier. There's a very little information on exercise and sleep (nothing you don't know) and no information about nutrition and he actually says not to take supplements.
If you are interested in all the current and recent studies on small creatures about the nitty gritty of what drugs and interventions *could* be in the pipeline for altering our bodies to hopefully evade aging sometime in the future, this is the book for you.
If you want to get healthy and stay healthy for a long time, there are far better books!
If you are interested in all the current and recent studies on small creatures about the nitty gritty of what drugs and interventions *could* be in the pipeline for altering our bodies to hopefully evade aging sometime in the future, this is the book for you.
If you want to get healthy and stay healthy for a long time, there are far better books!
February 14, 2021
Excellent book that explains why we age, treating the aging and living longer despite this. The methods of increasing lifespan currently in research stage - dietary restriction, senolytics, telemerase point to many possible interventions and drugs that could together increase healthy life. These could also delay cancers, heart disease, stroke and dementia. Meanwhile the author argues for a healthy lifestyle to be well and living and thus benefit from these treatments in a couple of decades or more.
April 8, 2021
Too speculative
This book is speculative to the point of near uselessness in practical terms. It’s interesting if you want to know about the earliest studies happening related to anti-aging, but there isn’t much that is actionable for today aside from the common sense advice of not smoking, eating a healthy balanced diet and exercising.
This book is speculative to the point of near uselessness in practical terms. It’s interesting if you want to know about the earliest studies happening related to anti-aging, but there isn’t much that is actionable for today aside from the common sense advice of not smoking, eating a healthy balanced diet and exercising.
March 28, 2021
Very interesting and compelling...
April 11, 2021
Gave me hope.
January 17, 2022
4.75 to 5.0. Very technical medical terminology makes it a tough read at times but well worth it. Fascinating throughout. Will be curious to see where the science goes over the years!!
April 2, 2023
Secret: I didn’t actually finish it
April 2, 2022
If you read one book on the biology of ageing, read this one. If you read a few, read this one first. Andrew Steele’s Ageless (2019) is the best nontechnical introduction available.
The chapters are grouped into three sections.
THE FIRST SECTION is an introduction to basic biology of ageing, including demography (what is ageing?—the fact that old have a higher risk of death than the young); evolution (why did ageing evolve?—natural selection cares less about late life, when you’ve already had a few offspring, than early life); the birth of modern biogerontology (via studying the mechanisms of modest life extension of the “caloric restriction� diet, and mutations like age-1 and daf-2 in C. elegans; things later matured further with the discovery of e.g. mTOR-inhibiting drugs like rapamycin, called “caloric restriction mimetics� for seeming to trick cells into thinking they’re calorically restricted); and cellular / molecular causes of ageing (following the “hallmarks of aging� framework).
The evolutionary puzzle of ageing was solved in the mid-20th century, although details remain; and the theory is conceptually neat and easy to learn (; cf. ). Steele lucidly explains the basic intuition, the declining force of natural selection w.r.t. age, and its roles in J. B. S. Haldane’s discussion of Huntington’s disease (1941); Peter B. Medawar’s mutation accumulation theory of ageing (1952); George C. Williams� antagonistic pleiotropy theory of ageing (1957); and the disposable soma theory, a version of antagonistic pleiotropy focused on metabolic resource allocation (Kirkwood and Rose, 1991). He doesn’t try to explain William D. Hamilton’s mathematical formalization of the declining force of selection intuition, as a pop-science book shouldn’t (1966; cf. Baudisch, 2005). He introduces George Williams� extrinsic mortality hypothesis, but not recent debates about its scope of applicability (Williams et al., 2006; see also Wensink et al., 2017). He introduces allometry and quarter-power scaling, though not by name or exponent, when he discusses heart rate, body size, and life span, such that elephants and mice have about the same number of heartbeats before dying (cf. Charnov, 1991; West et al., 1997). I learned about a neat hypothesis for the longevity of trees that I hadn’t heard!
The proximate biological processes of ageing are less well understood, and more tangled. Proximate biogerontology used to feel like a fact salad, in the absence of an organizing theoretical framework—while frameworks were hard to choose (Steele tells us of the old joke that there are more theories of ageing than scientists to study them!). But things have become more pedagogically accessible in recent years. Known ageing processes can be organized into categories, based on what type of damage they are and on how they might be treated (how many categories you want to use is a bit up to taste). This was the tack of Aubrey de Grey’s SENS program and its “� (de Grey, 2007), and of the more recent and more mainstream “� approach (named by López-Otín et al., 2013).* Steele explains that the criteria for including something as a hallmark of ageing are that it changes with age; accelerating it should accelerate ageing; and slowing it should slow ageing. Steele’s list is a bit modified from the 2013 list. Steele’s list is: 1. Trouble in the double helix: DNA damage and mutations; 2. Trimmed telomeres; 3. Protein problems: autophagy, amyloids, and adducts; 4. Epigenetic alterations; 5. Accumulation of senescent cells; 6. Power struggle: malfunctioning mitochondria; 7. Signal failure; 8. Gut reaction: changes in the microbiome; 9. Cellular exhaustion; 10. Defective defences: malfunction of the immune system. Again, he explains it all lucidly. It far from covers everything there is to know, but it’s a great place to start.
THE SECOND SECTION overviews approaches to treating the various hallmarks of ageing, which range from currently in mouse or even human trial (e.g. senolytics to clear away inflammatory senescent cells; giving lysosomes the missing enzymes needed to digest lipofuscin) to more speculative; Steele is careful never to exaggerate the status of any of the treatment options, nor the confidence in their hoped-for effects. No one treatment of any one hallmark will be the fountain of youth, but since hallmarks are likely upstream causes of multiple age-related diseases, treating them is expected to have more impact than addressing individual diseases individually; and in the long run, these and newer treatments may add up.
Steele organizes the treatment ideas into four chapters: Chapter 5: Out With the Old discusses removing accumulated harmful stuff, like lipofuscin and senescent cells; Chapter 6: In With the New discusses replenishing good things, including stem cell therapy and regenerating the thymus (an immune system organ that shrinks or “involutes�); Chapter 6: Running Repairs discusses protecting from and repairing DNA damage, including telomere extension and whether it could be done without increasing cancer risk; parabiosis and the presence of systemic factors in young blood (or the absence in young blood of old-blood factors); and transfer of mitochondrial genes to the safer nucleus, away from mitochondrial free radicals. Chapter 8: Reprogramming Aging is on recent research, which you might have heard Dr. David Sinclair talk about (2019), on the prospect of rewinding the recently-discovered “epigenetic clock,� as well as on more speculatively on systems-biology approaches that 21st century research should pursue.
Whenever you have an idea for a treatment, it raises the question: “Why hasn’t evolution already done this? Would us doing it have harmful side-effects?� (Compare to the perennial economists� challenge, “If that lunch is free why hasn’t somebody already eaten it?�) The book often does a fairly good job of remembering to address this question; not always, but often enough to prompt the reader to have the question in mind. For instance, one proposal for dealing with mitochondrial mutation is to help the 13 remaining mtDNA genes migrate to the more protected nucleus, like the others already have. But why haven’t they already? If it’s because it would be dangerous, then we shouldn’t do that. But it may just be for non-worrying reasons, such as that the mtDNA and nDNA “genetic codes� have diverged slightly, so a mitochondrial gene expressed in the nucleus would produce molecular gibberish (but since we know both genetic codes, we could just edit them accordingly) (Steele, 2019, pp. 213; 357; cf. de Grey, 2005).
THE THIRD SECTION stresses the moral case for treating the processes of ageing, as well as discussing political and regulatory practicalities: for instance, he discusses the upcoming TAME (Targeting Aging with Metformin) trial, led by Dr. Nir Barzilai, aiming to confirm observational reports that the well-known and safe diabetes drug metformin may have small beneficial effects on ageing; scientifically, this isn’t a big deal, since the effects if any are small; but in terms of the US regulatory system, it is a huge deal, since this is the first time the FDA has approved a trial to target ageing rather than an individual disease. Something I enjoyed about this section—for what I think it implies about the Zeitgeist—is how matter-of-fact it is about the moral case for treating ageing: of course we should help people have longer healthier lives, if there’s a chance we can. Once upon a time such a book might have had to spend pages grappling with such troll-philosophy questions as “But isn’t getting old and sick and turning into a corpse what gives life meaning?�; I think we’ve finally progressed beyond the need to entertain such cope.
As someone who does (evolutionary) ageing research, I was very impressed with Steele’s authorial choices, knowing what kind of objections laypeople raise, defusing them before they come up. “What if life extension is impossible?”—it isn’t, evolution did it repeatedly; Steele begins the book with this reminder, telling us in the introduction about negligibly senescent Galápagos tortoises. “Isn’t ageing just entropy?”—Steele reminds us in the first chapter that organisms aren’t closed systems; we can use energy from food to grow and repair ourselves. “Wouldn’t it be bad to live forever old and decrepit, like Tithonus, who wished for eternal life but forgot to wish for eternal youth?”—sure, but Steele repeatedly stresses that what we’re trying to do is treat ageing, so we can live younger and healthier for longer. He also pre-empts biologists� questions: “But didn’t George C. Williams theoretically prove in 1957 there are basically infinite causes of ageing, so it’s pointless to intervene in any of them?”—Steele argues No; Williams did argue something like that, but as far as we now know there are ten or so leading categories of age-related damage.** Steele’s asides, never intrusive, prove how comfortably he knows his audience—joking how telomeres are the only thing most people have ever heard about ageing biology, and how it’s cliché to say it’s cliché to say “the mitochondria is the powerhouse of the cell.�
For further reading, the endnotes of Steele’s book is a trove of recent review sources. Other recent pop-science books on ageing biology include David Stipp’s The Youth Pill (2010), Aubrey de Grey’s Ending Aging (2007), and David Sinclair’s Lifespan (2019). Stipp’s book is more focused on the caloric-restriction mimetics approach, and has more biographical flavour on individual biogerontologists; I recommend it after this one. Sinclair’s is valuable if you’re interested in his personal theories, but I think he overstates their confidence; it is great on the moral case for ageing research though, and on the spirit of excitement that biogerontology is no longer a backwater but a thriving field. Readers of Ending Aging will recognize some of the prospective treatments discussed in the second section: I see this section as a less detailed, but more up to date, sequel to that book; I do still recommend reading the earlier book as well if interested; those interested in keeping up with the latest news on the treating-hallmarks approach can follow the on YouTube, or the blog. The biggest difference between Steele and de Grey is their take on telomerase.
An introductory textbook is Roger McDonald’s Biology of Aging (2019); an older one if you want to see how the field has evolved is Alex Comfort’s The Biology of Senescence (1979). A technical series with new editions every few years is the Handbook of the Biology of Aging (e.g. Musi and Hornsby, 2021). The encyclopedic Bible of comparative biogerontology is Caleb Finch’s Longevity, Senescence, and the Genome (1990). An influential overview circa the 90s of the evolutionary genetics of ageing is Michael Rose’s Evolutionary Biology of Aging (1991; but see also Baudisch, 2005); the evolution of ageing is part of life history theory, so see also Stephen C. Stearns� The Evolution of Life Histories (1992). If you want to read a couple influential and accessible classic papers, check out Medawar’s “An unsolved problem of biology� (1952) and especially Williams� “Pleiotropy, natural selection, and the evolution of senescence� (1957); and to make explicit some of modern biogerontology’s common assumptions, see Richard A. Miller’s “Are there genes for aging?� (1999); notice that Williams and Miller disagree about whether ageing likely has a central clock. A valuable online resource is Dr. Joao Pedro de Magalhães� website , which contains biogerontology tutorials and links to a who’s-who in biogerontology, ageing genomics databases, etc.
Tl;dr Andrew Steele’s Ageless (2019) is excellently written, on a fascinating and important topic. Read it today!
References
Baudisch, A. (2005). Hamilton’s indicators of the force of selection. Proceedings of the National Academy of Sciences 102: 8263�8268.
Charnov, E. L. (1991). Evolution of life history variation among female mammals. Proceedings of the National Academy of Sciences 88: pp. 1134�1137.
Comfort, Al (1979). The Biology of Senescence (3rd ed.). Elsevier.
de Grey, A. (2005). Forces maintaining organellar genomes: is any as strong as genetic code disparity or hydrophobicity? BioEssays 27: 436�446.
de Grey, A. and Rae, M. (2007). Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime. St. Martin’s Griffin.
Fabian, D. and Flatt, T. (2011). The evolution of aging. Nature Education Knowledge 3: 9.
Fabian, D. and Flatt, T. (2012). Life history evolution. Nature Education Knowledge 3: 24.
Finch, C. E. (1990). Longevity, Senescence, and the Genome. Chicago University Press.
Gems, D. and de Magalhães, J. P. (2021). The hoverfly and the wasp: A critique of the hallmarks of aging as a paradigm. Ageing Research Reviews 70: 101407.
Haldane, J. B. S. (1941). New Paths in Genetics. George Allen & Unwin Ltd.
Hamilton, W. D. (1966). The moulding of senescence by natural selection. Journal of Theoretical Biology 12: 12�45.
Hanahan, D. and Weinberg, R. A. (2000). The hallmarks of cancer. Cell 100: 57�70.
Hanahan, D. and Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell 144: 646�674.
Kirkwood., T. B. L. and Rose, M. R. (1991). Evolution of senescence: Late survival sacrificed for reproduction. Philosophical Transactions: Biological Sciences 332: 15�24.
Lemoine, M. (2021). The evolution of the hallmarks of aging. Frontiers in Genetics 12: 693071.
López-Otín, C. et al. (2013). The hallmarks of aging. Cell 153: 1194�1217.
McDonald, R. B. (2019). Biology of Aging (2nd ed.). CRC Press.
Medawar, P. B. (1952). An unsolved problem of biology. In: Medawar, P. B. (1957). The Uniqueness of the Individual. Basic Books.
Miller, R. A. (1999). Kleemeier award lecture: Are there genes for aging? Journal of Gerontology: Biological Sciences 54A: B297–B307.
Musi, N. and Hornsby, P. (eds.) (2021). Handbook of the Biology of Aging (9th ed.). Academic Press.
Nesse, R. M. and Williams, G. C. (1994). Why We Get Sick: The New Science of Darwinian Medicine. Times Books.
Sinclair, D. A. (2019). Lifespan: Why we Age—And Why we Don’t Have To. Atria Books.
Stearns, S. C. (1992). The Evolution of Life Histories. Oxford University Press.
Steele, A. (2019). Ageless: The New Science of Getting Older Without Getting Old. Bloomsbury.
Stipp, D. (2010). The Youth Pill: Scientists at the Brink of an Anti-Aging Revolution. Current.
Wensink, M. J., Caswell, H., and Baudisch, A. (2017). The rarity of survival to old age does not drive the evolution of senescence. Evolutionary Biology 44: 5�10.
West, G. B., Brown, J. H., and Enquist, B. J. (1997). A general model for the origin of allometric scaling laws in biology. Science 276: 122�126.
Williams, G. C. (1957). Pleiotropy, natural selection, and the evolution of senescence. Evolution 11: 398�411.
Williams, P. D. et al. (2006). The shaping of senescence in the wild. Trends in Ecology and Evolution 21: 458�463.
* The term “hallmarks� was adopted from the earlier, influential oncology review paper “Hallmarks of cancer� (Hanahan and Weinberg, 2000; cf. 2011). Gems and de Magalhães, though respecting the pedagogical value of the hallmarks of aging framework, have discussed limitations to it as an explanatory paradigm, in comparison with the hallmarks of cancer, which is an explanatory paradigm that understands cancer as cells becoming able to proliferate on their own while escaping the body’s defences against rogue proliferation (Gems and de Magalhães, 2021). For a preliminary attempt to investigate the order and timing of the evolutionary history of the hallmarks of aging, see (Lemoine, 2021).
**Williams himself later became less confident in his argument, due in part to how it would seem to have predicted the caloric restriction response to be impossible; see the chapter on senescence in (Nesse and Williams, 1994).
The chapters are grouped into three sections.
THE FIRST SECTION is an introduction to basic biology of ageing, including demography (what is ageing?—the fact that old have a higher risk of death than the young); evolution (why did ageing evolve?—natural selection cares less about late life, when you’ve already had a few offspring, than early life); the birth of modern biogerontology (via studying the mechanisms of modest life extension of the “caloric restriction� diet, and mutations like age-1 and daf-2 in C. elegans; things later matured further with the discovery of e.g. mTOR-inhibiting drugs like rapamycin, called “caloric restriction mimetics� for seeming to trick cells into thinking they’re calorically restricted); and cellular / molecular causes of ageing (following the “hallmarks of aging� framework).
The evolutionary puzzle of ageing was solved in the mid-20th century, although details remain; and the theory is conceptually neat and easy to learn (; cf. ). Steele lucidly explains the basic intuition, the declining force of natural selection w.r.t. age, and its roles in J. B. S. Haldane’s discussion of Huntington’s disease (1941); Peter B. Medawar’s mutation accumulation theory of ageing (1952); George C. Williams� antagonistic pleiotropy theory of ageing (1957); and the disposable soma theory, a version of antagonistic pleiotropy focused on metabolic resource allocation (Kirkwood and Rose, 1991). He doesn’t try to explain William D. Hamilton’s mathematical formalization of the declining force of selection intuition, as a pop-science book shouldn’t (1966; cf. Baudisch, 2005). He introduces George Williams� extrinsic mortality hypothesis, but not recent debates about its scope of applicability (Williams et al., 2006; see also Wensink et al., 2017). He introduces allometry and quarter-power scaling, though not by name or exponent, when he discusses heart rate, body size, and life span, such that elephants and mice have about the same number of heartbeats before dying (cf. Charnov, 1991; West et al., 1997). I learned about a neat hypothesis for the longevity of trees that I hadn’t heard!
The proximate biological processes of ageing are less well understood, and more tangled. Proximate biogerontology used to feel like a fact salad, in the absence of an organizing theoretical framework—while frameworks were hard to choose (Steele tells us of the old joke that there are more theories of ageing than scientists to study them!). But things have become more pedagogically accessible in recent years. Known ageing processes can be organized into categories, based on what type of damage they are and on how they might be treated (how many categories you want to use is a bit up to taste). This was the tack of Aubrey de Grey’s SENS program and its “� (de Grey, 2007), and of the more recent and more mainstream “� approach (named by López-Otín et al., 2013).* Steele explains that the criteria for including something as a hallmark of ageing are that it changes with age; accelerating it should accelerate ageing; and slowing it should slow ageing. Steele’s list is a bit modified from the 2013 list. Steele’s list is: 1. Trouble in the double helix: DNA damage and mutations; 2. Trimmed telomeres; 3. Protein problems: autophagy, amyloids, and adducts; 4. Epigenetic alterations; 5. Accumulation of senescent cells; 6. Power struggle: malfunctioning mitochondria; 7. Signal failure; 8. Gut reaction: changes in the microbiome; 9. Cellular exhaustion; 10. Defective defences: malfunction of the immune system. Again, he explains it all lucidly. It far from covers everything there is to know, but it’s a great place to start.
THE SECOND SECTION overviews approaches to treating the various hallmarks of ageing, which range from currently in mouse or even human trial (e.g. senolytics to clear away inflammatory senescent cells; giving lysosomes the missing enzymes needed to digest lipofuscin) to more speculative; Steele is careful never to exaggerate the status of any of the treatment options, nor the confidence in their hoped-for effects. No one treatment of any one hallmark will be the fountain of youth, but since hallmarks are likely upstream causes of multiple age-related diseases, treating them is expected to have more impact than addressing individual diseases individually; and in the long run, these and newer treatments may add up.
Steele organizes the treatment ideas into four chapters: Chapter 5: Out With the Old discusses removing accumulated harmful stuff, like lipofuscin and senescent cells; Chapter 6: In With the New discusses replenishing good things, including stem cell therapy and regenerating the thymus (an immune system organ that shrinks or “involutes�); Chapter 6: Running Repairs discusses protecting from and repairing DNA damage, including telomere extension and whether it could be done without increasing cancer risk; parabiosis and the presence of systemic factors in young blood (or the absence in young blood of old-blood factors); and transfer of mitochondrial genes to the safer nucleus, away from mitochondrial free radicals. Chapter 8: Reprogramming Aging is on recent research, which you might have heard Dr. David Sinclair talk about (2019), on the prospect of rewinding the recently-discovered “epigenetic clock,� as well as on more speculatively on systems-biology approaches that 21st century research should pursue.
Whenever you have an idea for a treatment, it raises the question: “Why hasn’t evolution already done this? Would us doing it have harmful side-effects?� (Compare to the perennial economists� challenge, “If that lunch is free why hasn’t somebody already eaten it?�) The book often does a fairly good job of remembering to address this question; not always, but often enough to prompt the reader to have the question in mind. For instance, one proposal for dealing with mitochondrial mutation is to help the 13 remaining mtDNA genes migrate to the more protected nucleus, like the others already have. But why haven’t they already? If it’s because it would be dangerous, then we shouldn’t do that. But it may just be for non-worrying reasons, such as that the mtDNA and nDNA “genetic codes� have diverged slightly, so a mitochondrial gene expressed in the nucleus would produce molecular gibberish (but since we know both genetic codes, we could just edit them accordingly) (Steele, 2019, pp. 213; 357; cf. de Grey, 2005).
THE THIRD SECTION stresses the moral case for treating the processes of ageing, as well as discussing political and regulatory practicalities: for instance, he discusses the upcoming TAME (Targeting Aging with Metformin) trial, led by Dr. Nir Barzilai, aiming to confirm observational reports that the well-known and safe diabetes drug metformin may have small beneficial effects on ageing; scientifically, this isn’t a big deal, since the effects if any are small; but in terms of the US regulatory system, it is a huge deal, since this is the first time the FDA has approved a trial to target ageing rather than an individual disease. Something I enjoyed about this section—for what I think it implies about the Zeitgeist—is how matter-of-fact it is about the moral case for treating ageing: of course we should help people have longer healthier lives, if there’s a chance we can. Once upon a time such a book might have had to spend pages grappling with such troll-philosophy questions as “But isn’t getting old and sick and turning into a corpse what gives life meaning?�; I think we’ve finally progressed beyond the need to entertain such cope.
As someone who does (evolutionary) ageing research, I was very impressed with Steele’s authorial choices, knowing what kind of objections laypeople raise, defusing them before they come up. “What if life extension is impossible?”—it isn’t, evolution did it repeatedly; Steele begins the book with this reminder, telling us in the introduction about negligibly senescent Galápagos tortoises. “Isn’t ageing just entropy?”—Steele reminds us in the first chapter that organisms aren’t closed systems; we can use energy from food to grow and repair ourselves. “Wouldn’t it be bad to live forever old and decrepit, like Tithonus, who wished for eternal life but forgot to wish for eternal youth?”—sure, but Steele repeatedly stresses that what we’re trying to do is treat ageing, so we can live younger and healthier for longer. He also pre-empts biologists� questions: “But didn’t George C. Williams theoretically prove in 1957 there are basically infinite causes of ageing, so it’s pointless to intervene in any of them?”—Steele argues No; Williams did argue something like that, but as far as we now know there are ten or so leading categories of age-related damage.** Steele’s asides, never intrusive, prove how comfortably he knows his audience—joking how telomeres are the only thing most people have ever heard about ageing biology, and how it’s cliché to say it’s cliché to say “the mitochondria is the powerhouse of the cell.�
For further reading, the endnotes of Steele’s book is a trove of recent review sources. Other recent pop-science books on ageing biology include David Stipp’s The Youth Pill (2010), Aubrey de Grey’s Ending Aging (2007), and David Sinclair’s Lifespan (2019). Stipp’s book is more focused on the caloric-restriction mimetics approach, and has more biographical flavour on individual biogerontologists; I recommend it after this one. Sinclair’s is valuable if you’re interested in his personal theories, but I think he overstates their confidence; it is great on the moral case for ageing research though, and on the spirit of excitement that biogerontology is no longer a backwater but a thriving field. Readers of Ending Aging will recognize some of the prospective treatments discussed in the second section: I see this section as a less detailed, but more up to date, sequel to that book; I do still recommend reading the earlier book as well if interested; those interested in keeping up with the latest news on the treating-hallmarks approach can follow the on YouTube, or the blog. The biggest difference between Steele and de Grey is their take on telomerase.
An introductory textbook is Roger McDonald’s Biology of Aging (2019); an older one if you want to see how the field has evolved is Alex Comfort’s The Biology of Senescence (1979). A technical series with new editions every few years is the Handbook of the Biology of Aging (e.g. Musi and Hornsby, 2021). The encyclopedic Bible of comparative biogerontology is Caleb Finch’s Longevity, Senescence, and the Genome (1990). An influential overview circa the 90s of the evolutionary genetics of ageing is Michael Rose’s Evolutionary Biology of Aging (1991; but see also Baudisch, 2005); the evolution of ageing is part of life history theory, so see also Stephen C. Stearns� The Evolution of Life Histories (1992). If you want to read a couple influential and accessible classic papers, check out Medawar’s “An unsolved problem of biology� (1952) and especially Williams� “Pleiotropy, natural selection, and the evolution of senescence� (1957); and to make explicit some of modern biogerontology’s common assumptions, see Richard A. Miller’s “Are there genes for aging?� (1999); notice that Williams and Miller disagree about whether ageing likely has a central clock. A valuable online resource is Dr. Joao Pedro de Magalhães� website , which contains biogerontology tutorials and links to a who’s-who in biogerontology, ageing genomics databases, etc.
Tl;dr Andrew Steele’s Ageless (2019) is excellently written, on a fascinating and important topic. Read it today!
References
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Comfort, Al (1979). The Biology of Senescence (3rd ed.). Elsevier.
de Grey, A. (2005). Forces maintaining organellar genomes: is any as strong as genetic code disparity or hydrophobicity? BioEssays 27: 436�446.
de Grey, A. and Rae, M. (2007). Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime. St. Martin’s Griffin.
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Fabian, D. and Flatt, T. (2012). Life history evolution. Nature Education Knowledge 3: 24.
Finch, C. E. (1990). Longevity, Senescence, and the Genome. Chicago University Press.
Gems, D. and de Magalhães, J. P. (2021). The hoverfly and the wasp: A critique of the hallmarks of aging as a paradigm. Ageing Research Reviews 70: 101407.
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McDonald, R. B. (2019). Biology of Aging (2nd ed.). CRC Press.
Medawar, P. B. (1952). An unsolved problem of biology. In: Medawar, P. B. (1957). The Uniqueness of the Individual. Basic Books.
Miller, R. A. (1999). Kleemeier award lecture: Are there genes for aging? Journal of Gerontology: Biological Sciences 54A: B297–B307.
Musi, N. and Hornsby, P. (eds.) (2021). Handbook of the Biology of Aging (9th ed.). Academic Press.
Nesse, R. M. and Williams, G. C. (1994). Why We Get Sick: The New Science of Darwinian Medicine. Times Books.
Sinclair, D. A. (2019). Lifespan: Why we Age—And Why we Don’t Have To. Atria Books.
Stearns, S. C. (1992). The Evolution of Life Histories. Oxford University Press.
Steele, A. (2019). Ageless: The New Science of Getting Older Without Getting Old. Bloomsbury.
Stipp, D. (2010). The Youth Pill: Scientists at the Brink of an Anti-Aging Revolution. Current.
Wensink, M. J., Caswell, H., and Baudisch, A. (2017). The rarity of survival to old age does not drive the evolution of senescence. Evolutionary Biology 44: 5�10.
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* The term “hallmarks� was adopted from the earlier, influential oncology review paper “Hallmarks of cancer� (Hanahan and Weinberg, 2000; cf. 2011). Gems and de Magalhães, though respecting the pedagogical value of the hallmarks of aging framework, have discussed limitations to it as an explanatory paradigm, in comparison with the hallmarks of cancer, which is an explanatory paradigm that understands cancer as cells becoming able to proliferate on their own while escaping the body’s defences against rogue proliferation (Gems and de Magalhães, 2021). For a preliminary attempt to investigate the order and timing of the evolutionary history of the hallmarks of aging, see (Lemoine, 2021).
**Williams himself later became less confident in his argument, due in part to how it would seem to have predicted the caloric restriction response to be impossible; see the chapter on senescence in (Nesse and Williams, 1994).
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