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<p>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, it 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.</p>

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Deciphering the timing and impact of life-extending interventions: temporal efficacy profiler distinguishes early, midlife, and senescence phase efficacies

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月19日

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  • Nisi Jiang,
  • Catherine J. Cheng,
  • Qianqian Liu,
  • Randy Strong,
  • Jonathan Gelfond,
  • James F. Nelson

摘要

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, it 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.