Review of David Sinclair's Lifespan

Lifespan: Why We Age, and Why We Don't Have To is a 2019 non-fiction book authored by Harvard biologist David Sinclair with journalist Matthew LaPlante. Aging is the increasing probability of death from internal causes. Why do most animals age instead of growing healthier and healthier which each passing year? Sinclair's "information theory of aging" posits that aging is the result of the accumulation of epigenetic damage. He believes certain enzymes, called sirtuins, have the dual function of repairing genomic damage and maintaining epigenetic integrity. He hypothesizes that this dual role is a remnant of an ancient survival circuit that suppressed replication epigenetically in response to DNA damage. Sinclair argues that DNA damage, which occurs as a byproduct of life, first distracts sirtuins from their epigenetic maintenance role. This, in turn, leads to the epigenetic damage accumulation that causes aging.

Seems to think that the body has two modes: (1) growth and reproduction and (2) repair.

Sinclair's evidence for this theory is as follows.

Aging, undoubtedly, has group-fitness benefits. For example, aging gives the young a competitive advantage, aging limits population growth in times of abundance, and aging removes bad-for-the-group individuals (for example, a king that has a proclivity for war, a saint that is a chronic carrier of disease, or a generation of people with a pernicious worldview). However, each of these group-benefits are also kin-benefits. Aging gives the young a competitive advantage with their older relatives, aging limits the size of a family in times of plenty, and aging removes bad-for-the-family individuals from the family. If aging is selected for by evolution, it is still not clear whether it is group-selected or kin-selected.

Evolution has not selected for longevity because (1) not-aging has a reproduction cost; and (2) evolution cannot select for longevity passed external mortality.

In fact, Sinclair hypothesizes that lifespans will double by natural selection simply because human innovation has made external mortality miniscule.

can allocate resources to reproduction or longevity, but not both.

Allocate resources for reproduction and intelligence, reproduction and strength, reproduction and speed, why not both reproduction and longevity.

In the 1950s, however, it become discredited to believe evolution could select for a characteristic because of its group-fitness benefits. Rather, mainstream biologist believe that any characteristic that has group-fitness benefits was selected for its individual-fitness or kin-fitness benefits and just happens to have group-fitness benefits.

Sinclair's theory of aging belongs to a larger class of theories that posit that aging is the result of some type of damage accumulation. The damage-accumulation theories argue that evolution does not have the ability to select for longevity passed external mortality. Specifically, an organism cannot evolve mechanisms to prevent damage from accumulating passed the time when it would have died anyways due to external causes. If this were true, however, then aging would largely be an artifact of the laboratory - only affecting animals protected from external mortality. However, there is now over 100 years of field studies that demonstrate that most animals in nature do in fact die of aging. When a gazelle is eaten by a lion, the lion is a comorbidity and not the cause of death. When studied thoroughly, it becomes clear that this gazelle was eaten because it was at the back of the pack because its body was exponentially losing its ability to function. This gazelle died of aging. Thus, evolution should have selected for longevity if it was indeed trying to maximize individual fitness.

The external mortality theories believe that we live in a dog-eat-dog world. As Sinclair writes, "The circuit begins with gene A, a caretaker that stops cells form reproducing when times are tough. This is key, because on early planet Earth, most times are tough." Most organisms are well-adapted to their environment. Predators prey just lightly on top of prey populations. Times are not tough now, and probably were not tough then.

"Sometimes brutish and sometimes bounteous"

singular reason

There is a well-known correlation between external mortality and longevity.

Quotes

"I propose the reason this gene circuit is conserved is that it is a rather simple and elegant solution to the challenges of a sometimes brutish and sometimes bounteous world that better ensures the survival of the organisms that carry it." (p. 7)