Why We Age

BioViva Science
11 min readAug 10, 2022


Why do we age?

All adaptations should improve an organism’s chance of producing viable offspring.

Shouldn’t they?

If this was true, species with abnormally long reproductive windows should rule across kingdoms and clades. This simplistic interpretation of natural selection would guarantee increasingly lengthy lifespans for all. Now, nearly four billion years since the first single-celled organisms, negligible senescence — remaining youthful up to the very end of life — should be the norm.

This line of inquiry may seem daft. There are physical limitations to how long anything can last, surely. Yet these mechanical explanations, these appeals to “wear-and-tear,” hardly account for the vastly different lifespans of closely related animals. They compare (or rather, confuse) sophisticated self-renewing systems with simple machines. More importantly, they aren’t easily reconciled with the evidence at hand.

A Mayfly lives for twenty-four hours. A termite queen can live for half a century (or, according to some entomologists, even longer). Myotis myotis lives for 35 years, 30 years longer than some of their relatives. This is likely because twenty-one genes associated with telomere protection are upregulated in the Mouse-Eared Bat. However, telomeric integrity (or lack thereof) is just one way aging can be modulated.

To the chagrin of marsupial enthusiasts everywhere, the North American opossum lives less than two years in the wild and, at most, four in captivity. Yet a colony on Sapelo Island lives between 25 to 50% longer than mainlanders (they also have fewer offspring). A few thousand years of isolation, a blink of the eye in evolutionary time, yielded a substantial shift — the equivalent of additional decades for an animal like ourselves. Still, these anecdotes don’t explain senescence, why our joints start to ache or our thinking begins to slow. There seems to be no point in what amounts to planned obsolescence.

Does aging serve an evolutionary purpose?

It would not appear so. Frailty, infertility, and death are clearly not advantageous if the whole of the law is to be fruitful and multiply, yet all three are the fate of most animals (negligibly senescent organisms largely avoid the first two). After maturity, programmed events (like menopause) and quasi-programmed ones like telomere shortening are undeniably deleterious.

Asexual reproduction is a rarity for multicellular organisms. Homogenous populations are susceptible to obliteration, not just by pathogens but by collectively failing to keep up with their surroundings. Certain members of each new generation, however minutely, may be better suited to their environment (or some future iteration thereof) than their forebears. If aging is programmed, what is the secret to longevity?

There isn’t one, not just one anyway.

Patterns are marred by outliers. For example, body size is linked with longevity between species (e.g. a whale versus a mouse — within a species, the inverse is often true, think of Great Danes). Humans are an exception, living five times longer than expected based on our size. Marsupials have lower body temperatures and basal metabolic rates than placentals, but are generally short-lived. Different species of sea urchin have massively different lifespans (five versus fifty), yet no significant differences in telomere length or loss have been recorded.

In other words, there are many ways to get old and just as many to stay young. Comparative biology is an ongoing source of inspiration for those interested in understanding and managing the aging process.

Consider the Lighthouse jellyfish, which not only avoids frailty and infertility but also, while it eludes predation, death itself. They are biologically immortal. Now, no doubt their relatively few moving parts contribute to their facility for regeneration. The simpler and younger (which isn’t always chronological), the better equipped an organism is to rebuild itself.

When injured or threatened, the Lighthouse jellyfish returns to a polyp phase. Muscle cells of its temporary entombment transform into nerve cells, arms sprout, and a new mouth takes shape. This isn’t a process mammals can readily mimic, but jellyfish hardly have a monopoly on self-repair. A wriggling lizard’s tail is for many an indelible childhood memory. Not to damper anyone’s sense of wonder, but their replacement tails are cartilage tubes without spinal columns or nerves.

A happy axolotl

The amphibians can claim more impressive feats of regeneration. Tadpoles become frogs, but olms and axolotls forgo metamorphosis altogether. The retention of juvenile characteristics is called neoteny. Their Peter Pan approach serves them well. By retaining their gills they can live underwater and, instead of sprouting a facsimile of a tail, axolotls can regrow fully functional limbs (up to five times) and internal organs. While they are among the most remarkable practitioners of bodily restoration, they are not especially long-lived. Salamander species live between three to one hundred years; the axolotl falls at the lower end at ten to fifteen.

Heroic acts of recovery do not best consistent maintenance.

Olms, also called cave salamanders, sit at the high end. They are sedentary, moving only to feed and reproduce (every twelve and a half years). Having no predators, they lead enviable existences bereft of stress. Recent research suggests their slow lifestyle reduces the production of free radicals, as they do not have any unique antioxidant mechanisms. Their basal metabolic rate is not lower than other salamanders (although, in times of scarcity, it can be drastically reduced). Unconvinced wear-and-tearers may think it’s unfair to dwell on the aspects of aging that seem programmed while ignoring the accumulation of junk and damage.

However alluring it may be, the analogy between oxidative damage and rusting should be set aside. Exercise generates oxidative stress, yet study after study finds new reasons to engage in regular physical activity, including a reduction in most causes of mortality. As we are not olms, spending our days in a recliner probably won’t keep us young. Yes, physical activity generates free radicals, but our response to it protects us from them by bolstering our defenses.

Denham Harmon proposed that free radical damage is the main culprit behind aging. The ongoing obsession with antioxidants is a direct descendant of Harman’s theory. The conclusion, like the premise, is predictably flawed. This fad has been tempered by dietary studies showing excessive antioxidant consumption can be detrimental. In all fairness, the experimental evidence was on Harmon’s side for some time. Lower levels of reactive oxygen species (ROS) production has been linked with longer lifespans in a variety of animals. On the other hand, bats and white-footed mice have similar levels of ROS production but a four-fold difference in lifespans. There’s also no difference between mice and naked mole rats in this area.

Meet H. glabber, the naked mole rat. These blind and negligibly senescent animals live in colonies like ants and bees. They live for thirty-two years, about three decades more than similarly sized rodents. Several studies show they sustain substantial oxidative damage early on, yet enjoy good health throughout their exceptionally long lifespans. It’s been suggested that oxidative damage is hormetic for them, the way exercise is for us. The damage does not keep accruing like it does for mice. It reaches a certain point and then stops. H. Glabber is resistant to protein unfolding and shows lower levels of protein degradation. Unusually dense hyaluronic acid protects them from cancer.

Their underground lifestyles help them avoid predation.

Larger bodies have slower metabolisms, which was the widely accepted explanation for why whales outlive shrews. There is probably some truth to this, but it’s clear that protection from predation also allows longer lifespans to evolve (remember the opossums?).

Mice with reduced SOD2 (which clear mitochondrial ROS) accumulate more DNA damage and have higher rates of cancer than control groups, but their lifespans are not measurably reduced by this massive defect in their antioxidant defense system. Resistance to oxidative stress is helpful, but it doesn’t account for why animals become increasingly predisposed to infirmity with time. Senescence appears to be largely independent of oxidative damage, having more in common with puberty, menopause, and other programmed events than the rusting of a boat. When it is especially unfavorable to a species, they find a way around it or go extinct.

Getting old is not for the birds.

Their sizes and metabolic rates would suggest they should quickly exit life’s stage, but this is not the case. Flight is not for the faint of heart or limb. This vigorous activity is their meal ticket; it should make sense that senescence is strongly selected against in winged animals.

This may all seem needlessly complicated. Parsimony would tell us aging is not planned. It’s a byproduct, the unfortunate result of nature’s unyielding indifference. A few figureheads claim we age because evolution ceases to care about us after reproduction. This is probably not the case for animals that raise their children or contribute to rearing their extended kin. Any species with a culture, like our own, benefits immensely from enhanced longevity.

One extension of this is antagonistic pleiotropy, which claims some genes are beneficial in youth, but become deleterious with time. Examples include the role androgens play in masculinization and, later on, prostate cancer. Thymic regeneration, the reconstruction of a crucial part of the immune system, has been jump started in mice by blocking androgen. Male pattern baldness is also driven in part by these hormones (although baldness doesn’t seem to universally reduce reproductive success).

Still, it hardly accounts for all of the phenomena explored so far. It suggests most improvements in longevity would come at the expense of reproductive success. The originators of this theory were speculating before Watson and Crick, when Mendelian genetics was still the cutting edge and the concept of gene expression was unknown. It is now known that gene expression is carefully controlled; its coordination is what causes us to mature, heal, and yes, in all likelihood, become debilitated.

If genes can be turned on and off, why should there be a tradeoff of any kind? Antagonistic pleiotropy assumes the field has an immutable topography, when nothing could be farther from the truth. Epigenetic clocks, with substantial evidence behind their predictive powers, show that changes to DNA methylation are associated with the aging process. These epigenetic events are not completely random. For that matter, aging in any given species is far from random. It follows a fairly predictable trajectory. Granted, it is more foreseeable for some than others.

Antechinus, the world’s most oversexed mammal, looks surprisingly grumpy.

Salmon are the best-known examples of semelparity. After mating they suddenly develop an assortment of age-related ailments. These sudden changes are allegedly set in motion by a surge of cortisol following coitus. What about mammals? Mammals have to stick around. Although, Antechinus could be considered semelparous. A marsupial that looks like a cross between a rat and a shrew, males mate for 14 hours at a time. They keep it up until their fur falls out, their internal organs disintegrate, and their immune systems crumble. Their sacrifice frees up food by seasonally slashing the population in half.

Semelparous animals can be dismissed as exceptions. Yet they show, albeit more dramatically, what the evidence presented suggests — aging is, in a simple or a complex manner, modulated by an array of processes. Some are simple — the axolotl will transform if given thyroxine — while others involve multiple parts, like the naked mole rat’s litany of adaptations. When and where it has been necessary, biological systems have found ways to delay or hasten its course. Humans have 1000 times as many cells as mice and live 30 times as long. Species with more cells should be prone to cancer, but this is not the case.

This is Peto’s Paradox.

Whales, elephants, and humans have extensive antioncogenic bastions because becoming riddled with tumors by adolescence does not fit their reproductive strategies. Antagonistic pleiotropy advocates act as though our bodies are just a set of gears and pulleys. Tradeoffs exist, of course, but the list of either-ors is shorter than they think. Nature finds creative workarounds.

The way arthropods breathe imposes a hard limit on their size (it’s also why they were so massive in the oxygen-rich Carboniferous), but why we become feeble and die does not come from something as straightforward as a surface area equation. Biological organisms are complex adaptive systems that have been sculpted by, to borrow Monod’s phrase, chance and necessity. Amidst all of these intricacies, there is a growing list of genes that enhance healthspan and lifespan. Nature shows us that even aging is malleable.

Technologies like gene therapy have the potential to tap into this treasury of secrets to let humans remain youthful for longer.

Authored by Adam Alonzi

Adam is a writer, independent researcher, documentary maker, and author of two novels. He is the director of marketing for BioViva Science. Visit adamalonzi.com for more.

References and Suggested Reading

Andziak, Blazej, et al. “High oxidative damage levels in the longest‐living rodent, the naked mole‐rat.” Aging cell 5.6 (2006): 463–471.

Austad, Steven N., and Jessica M. Hoffman. “Is antagonistic pleiotropy ubiquitous in aging biology?.” Evolution, medicine, and public health 2018.1 (2018): 287–294.

Austad, Steven N. “The comparative biology of mitochondrial function and the rate of aging.” Integrative and comparative biology 58.3 (2018): 559–566.

Buffenstein, Rochelle. “The naked mole-rat: a new long-living model for human aging research.” The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60.11 (2005): 1369–1377.

Caulin, Aleah F., and Carlo C. Maley. “Peto’s Paradox: evolution’s prescription for cancer prevention.” Trends in ecology & evolution 26.4 (2011): 175–182.

Dali‐Youcef, Nassim, et al. “Sirtuins: the ‘magnificent seven’, function, metabolism and longevity.” Annals of medicine 39.5 (2007): 335–345.

Foley, Nicole M., et al. “Drivers of longitudinal telomere dynamics in a long‐lived bat species, Myotis myotis.” Molecular Ecology 29.16 (2020): 2963–2977.

Goldsmith, Theodore C. The Evolution of Aging: How new theories will change the future of medicine. Azinet, 2006.

Goldsmith, Theodore C. “On the programmed/non-programmed aging controversy.” Biochemistry (Moscow) 77.7 (2012): 729–732.

Ioviţă, Anca. The Aging Gap Between Species. Anca Ioviţă, 2016.

Kaiser, Alexander, et al. “Increase in tracheal investment with beetle size supports hypothesis of oxygen limitation on insect gigantism.” Proceedings of the National Academy of Sciences 104.32 (2007): 13198–13203.

Martell, L., et al. “Life cycle, morphology and medusa ontogenesis of Turritopsis dohrnii (Cnidaria: Hydrozoa).” Italian Journal of Zoology 83.3 (2016): 390–399.

McCusker, Catherine, and David M. Gardiner. “The axolotl model for regeneration and aging research: a mini-review.” Gerontology 57.6 (2011): 565–571.

Munro, Daniel, et al. “The exceptional longevity of the naked mole‐rat may be explained by mitochondrial antioxidant defenses.” Aging Cell 18.3 (2019): e12916.

Holmes, D. J., R. Flückiger, and S. N. Austad. “Comparative biology of aging in birds: an update.” Experimental gerontology 36.4–6 (2001): 869–883.

Howes, Randolph M. Reactive Oxygen Species Vs. Antioxidants: The Oxypocalypse Or the War that Never was. Free Radical Publ., 2014.

Lindstedt, S. L., and W. A. Calder III. “Body size, physiological time, and longevity of homeothermic animals.” The Quarterly Review of Biology 56.1 (1981): 1–16.

Ricklefs, Robert E. “Insights from comparative analyses of aging in birds and mammals.” Aging cell 9.2 (2010): 273–284.

Saldmann F, Viltard M, Leroy C, Friedlander G. The Naked Mole Rat: A Unique Example of Positive Oxidative Stress. Oxid Med Cell Longev. 2019 Feb 7;2019:4502819. doi: 10.1155/2019/4502819. PMID: 30881592; PMCID: PMC6383544.

Salmon, Adam B., et al. “The long lifespan of two bat species is correlated with resistance to protein oxidation and enhanced protein homeostasis.” The FASEB Journal 23.7 (2009): 2317–2326.

Skulachev, Vladimir P., et al. “Neoteny, prolongation of youth: from naked mole rats to “naked apes” (humans).” Physiological reviews (2017).

Speakman, John R., and Colin Selman. “The free‐radical damage theory: accumulating evidence against a simple link of oxidative stress to ageing and lifespan.” Bioessays 33.4 (2011): 255–259.

Sutherland, Jayne S., et al. “Activation of thymic regeneration in mice and humans following androgen blockade.” The Journal of Immunology 175.4 (2005): 2741–2753.

Tasaki, Eisuke, Mamoru Takata, and Kenji Matsuura. “Why and how do termite kings and queens live so long?.” Philosophical Transactions of the Royal Society B 376.1823 (2021): 20190740.

Voituron, Yann, et al. “Extreme lifespan of the human fish (Proteus anguinus): a challenge for ageing mechanisms.” Biology Letters 7.1 (2011): 105–107.



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