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Aging01:26

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Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
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First-generation versus next-generation epigenetic aging clocks: Differences in performance and utility.

Adiv A Johnson1, Maxim N Shokhirev2

  • 1Tally Health, New York, NY, USA. adiv@tallyhealth.com.

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|June 18, 2025
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Summary
This summary is machine-generated.

Next-generation epigenetic aging clocks, trained on health outcomes, show greater association with health signals and responsiveness to interventions than first-generation clocks. Prioritize next-generation models for health and interventional studies.

Keywords:
Age-related outcomesAging biomarkerEpigenetic aging clockFirst-generation clockMortality riskNext-generation clock

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Area of Science:

  • Epigenetics
  • Biomarkers
  • Aging Research

Background:

  • Epigenetic aging clocks predict biological age using methylomic data.
  • First-generation clocks predict chronological age.
  • Next-generation clocks are trained on health, lifestyle, and age-related outcomes.

Purpose of the Study:

  • Define and differentiate first-generation versus next-generation epigenetic clocks.
  • Summarize existing next-generation clocks, their training, and accessibility.
  • Tabulate literature on interventions influencing epigenetic clocks.

Main Methods:

  • Review and define epigenetic clock generations.
  • Compile and describe existing next-generation clocks.
  • Systematically review intervention studies impacting epigenetic clocks.

Main Results:

  • Next-generation clocks associate with more health/disease signals than first-generation clocks.
  • Next-generation clocks are more predictive of age-related outcomes and interventions.
  • Evidence supports interventions influencing epigenetic aging clocks.

Conclusions:

  • Next-generation epigenetic clocks offer greater utility for health-related research.
  • Prioritize next-generation models for association and interventional studies.
  • Further sub-categorization of next-generation clocks may be beneficial.