First-generation versus next-generation epigenetic aging clocks: Differences in performance and utility.

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.