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Aging by the clock and yet without a program
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AI
DOI：10.1038/s43587-025-00975-2.png)
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Abstract
En 中文
The mechanisms of aging are becoming increasingly well mapped; however, there remains ongoing debate about the ultimate and proximate causes of aging. The recent development of highly precise aging clocks led to a resurgence of arguments in support of a biological program of aging. However, the declining force of natural selection after the onset of reproduction means that cellular function could deteriorate without requiring a specific program. Here, we argue that aging clocks do not imply an intrinsic program but rather reflect the stochastic accumulation of molecular errors and damage. Damage accumulates due to insufficient maintenance and repair and contributes to system-wide entropy. In support of this, cross-species comparisons indicate that enhanced DNA repair capacity is a key determinant of exceptional longevity in mammals. By better understanding the nature of the stochasticity that governs the aging process, we will have a stronger mechanistic basis for developing geroprotective interventions to promote healthy aging in humans. Meyer and colleagues refute the idea that, as aging can be tracked precisely by clocks, it must be driven by a biological program. They propose that imperfect maintenance and repair processes resulting from a selection shadow facilitate the accumulation of stochastically occurring damage, which in turn advance the aging process with the precision of a clock.
Keywords:
Aging clocks
Stochastic damage accumulation
Biological program
Natural selection
DNA repair
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