Sign in with Facebook
David Bahry's Reviews > Ageless: The New Science of Getting Older Without Getting Old
Ageless: The New Science of Getting Older Without Getting Old
by
by
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
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).
Sign into ŷ to see if any of your friends have read
Ageless.
Sign In »
Reading Progress
Finished Reading
July 13, 2021
– Shelved
Comments Showing 1-1 of 1 (1 new)
date
newest »
newest »
message 1:
by
Elizabeth
(new)
Jul 18, 2021 07:00AM
great review David! I learned things
reply
|
flag
