Back to Debating Limits to Human Life Span Again

While it is self-evident that longevity is limited in the practical sense, in that one or more degenerative processes of aging eventually make it so unlikely for survival to continue that everyone dies somewhere before age 120, that doesn't mean that longevity is limited in any other sense. If we alter the consequences of the underlying processes of aging, by repairing the damage that they cause, by changing the process, and so forth, then longevity will increase. While the authors of today's open access paper make generally sensible statements about the nature of aging, they seem far too skeptical that anything of practical use can be achieved in the near future in the field of rejuvenation research. They mount an argument from complexity, against the ability to increase maximum life span from any single intervention into processes of aging, that doesn't seem at all sound to me.

If anything, the demonstrated network of interactions between processes of aging, and between processes and cellular metabolism, is an argument for addressing any one process to be broadly beneficial, eliminating harmful effects throughout cellular biochemistry and tissue function. That evolution has not produced this outcome in any given species is not an argument against the benefits of, for example, removing senescent cells from aging tissues. It is more an argument against the idea that evolutionary selection operates strongly on matters relating to later life. Species lifespan is most likely a consequence of evolutionary pressures operating on the early life environment, a byproduct of that tooth and nail competition, not a selected outcome.

Why Gilgamesh failed: the mechanistic basis of the limits to human lifespan

Thus far, geroscience has been remarkably successful in increasing our insight into aging and convincingly demonstrating that lifespan, at least mean lifespan, as well as healthspan, can be modulated, based on interventions targeting the molecular pathways first discovered in the worm. What it has not done, however, is demonstrate that the maximum lifespan of a vertebrate can be radically extended. The possibility of doing just that, however, is suggested by the large diversity of mortality curves across species.

Confidence in technological progress has now become so high that it has been argued that new medical interventions will soon emerge and radically increase human longevity. Such optimism is the driving force behind the very large sums of money recently donated by billionaires to new organizations active in geroscience. These include: the Methuselah Foundation, which has set up a series of prizes to demonstrate longevity extension in mice; the SENS Research Foundation, which has funded research into aging and rejuvenation; Calico, launched by Google, has engaged in multiple collaborations with academic and commercial researchers; Human Longevity, founded by Craig Venter of human genome fame, and largely focused on a concierge longevity service; and Altos Labs, a newcomer with $3 billion of funding.

Despite their impressive rosters and large cash flows, these organizations face great difficulty in achieving their lofty goals. Currently, there is little consensus as to the cause, or causes, of aging. Most would agree that aging is the result of damage, that is, deleterious changes, that are ultimately molecular in nature. Although preventative measures can be useful, a damage-repair approach, like the one advocated by the SENS Research Foundation and others, will be necessary

While in theory targeting cellular defense systems, including systems for DNA repair, detoxification, immune response and programmed cell death, to boost the quick removal of damage to biological macromolecules, protein aggregates, and senescent cells, should be feasible in the long term, singular causes of aging are conflicting with evolutionary theory. Indeed, if there would be one highly conserved central cause of aging, possibly going back in evolutionary time to the early replicators, multicellular organisms would fall prey to the late-life adverse effects of mutations that accumulate in the germline due to the age-related decline in efficacy of natural selection. This would mean that, independent of any hypothetical central cause of aging, a host of additional adverse late-life effects have to be taken into account.

This would essentially mean that any fix of the limits to lifespan would require interventions at many choke points. Such multipoint targeting would also need to be fine-balanced so as to avoid side effects. Indeed, there are few if any gene regulatory pathways exclusively involved in somatic maintenance and it is this complexity that essentially rules out successful interventions aiming to exclusively extend maximum lifespan of a species. In essence, what needs to be done is to mimic evolution as to how this gave rise to extremely long-lived species, such as those mentioned above, but in real time. As this would involve possibly millions of genetic variants, this seems an impossible quest.

Based on the above, geroscientists should clearly distinguish between mean and maximum lifespan and not give the impression that their research can substantially increase the current limits to human lifespan. Their focus should be on improving life expectancy and healthspan, that is, bringing more people closer to the maximum lifespan possible for members of Homo sapiens and improving the quality of those years.