Metabolism is exceedingly complex, and incompletely understood. This is true of individual cells, let alone organisms made up of very large numbers of those cells. Most of the work done on interventions intended to slow aging takes the form of attempts to alter metabolism into a more favorable state in which aging progresses at a modestly slower pace, usually via the use of small molecules. This approach is doomed to failure at this stage of technological progress. We do not know enough of metabolism, we cannot control enough of metabolism. Studies show that combining any two marginally aging-slowing small molecules is as likely as not to produce an interaction that results in a marginal acceleration of aging. Similarly, researchers here demonstrate that a sizable fraction of marginally aging-slowing interventions only work at certain ages, and become marginally aging-accelerating at other ages. And at the end of the day, why is so much of the focus placed on interventions that cannot achieve more than a small benefit?
A growing number of compounds are reported to extend lifespan, but it remains unclear whether they reduce mortality across the entire life course or only at specific ages. This uncertainty persists because the commonly used log-rank test cannot detect age-specific effects. Here, we introduce a new analytical method that addresses this limitation by revealing when, how long, and to what extent interventions alter mortality risk.
Applied to survival data from 42 compounds tested in mice by the National Institute on Aging Interventions Testing Program, our method identified 22 that reduced mortality at certain ages, more than detected by the log-rank test, while 15 increased mortality at certain ages. Most compounds were effective only within restricted age ranges; just 8 reduced mortality late in life, when burdens of aging are greatest. Compared to conventional methods, this approach uncovers more beneficial and harmful effects, offers deeper insight into timing and mechanism, and can guide development of future anti-aging therapies.
Link: https://doi.org/10.1038/s41467-025-65158-4
View the full article at FightAging
