Today's open access paper illustrates one of the many issues inherent in the study of the biochemistry and genetics of exceptionally long-lived people, which is that the data from various different initiatives rarely agrees. The effects of individual or even groups of gene variants are small and hard to pin down. Past studies have suggested that exceptional longevity is correlated with a lack of cardiovascular risk factors, whether genetic or measured aspects of biochemistry such as lipid levels in blood. That seems a sensible hypothesis: cardiovascular disease removes people from the population, therefore older cohorts should exhibit fewer signs of risk for cardiovascular disease. Yet that is not the case in the work presented here: there is no good association between longevity and lesser presence of risk factors.

What this sort of distribution of results should tell us is that the biochemistry of exceptional human longevity is a poor area of study if the goal is to produce reliable therapies with large effects on human aging. Old people who survive to very late life do so largely because they are either lucky (in exposure to pathogens, in the way in which the damage of aging progressed in a stochastic manner in their case) or because they made good lifestyle choices for much of their span of years. Or both. Beneficial genetic variants and consequent differences in cellular metabolism appear to confer only very modest increases in the odds of living for a long time, and even for those people who do live longer, the impact of degenerative aging is very significant. An environment of small, unreliable effects should be skipped in favor of research strategies with larger potential gains at the end of the day.

Exceptional Longevity and Polygenic Risk for Cardiovascular Health