Longitudinal changes in epigenetic clocks predict survival in the InCHIANTI cohort.

Longitudinal acceleration of multiple epigenetic clocks was associated with increased mortality risk independent of baseline epigenetic age.

• Study included 699 adults from the InCHIANTI cohort followed for up to 24 years.
• First-, second-, and third-generation epigenetic clocks were evaluated.
• Associations were independent of baseline epigenetic age and other confounders.
• The study assessed temporal acceleration (rate of change) rather than cross-sectional epigenetic age measurements.

Dynamic changes in epigenetic aging reflect evolving health status beyond what is captured by baseline epigenetic age measurements.

• Cross-sectional assessments of epigenetic age have been linked consistently to health outcomes and lifespan in prior work.
• The longitudinal rate of change in epigenetic clocks provided additional insight into aging trajectories beyond baseline measures.
• The findings suggest dynamic epigenetic changes may serve as sensitive indicators for interventions aimed at extending healthspan and longevity.
• Multiple clock generations (first, second, and third) were examined to assess robustness across different clock methodologies.

The InCHIANTI cohort provided a longitudinal framework of up to 24 years of follow-up for evaluating epigenetic clock dynamics in 699 adults.

• Sample size was 699 adults.
• Follow-up duration was up to 24 years.
• The study design was longitudinal, allowing assessment of within-person temporal changes in epigenetic clocks.
• Mortality was used as the primary outcome for evaluating the prognostic value of epigenetic clock acceleration.

Epigenetic clocks derived from DNA methylation patterns capture molecular signatures that predict morbidity and mortality beyond chronological age.

• Multiple generations of epigenetic clocks exist, including first-, second-, and third-generation clocks.
• These clocks are described as 'among the most promising biomarkers of biological aging.'
• Prior cross-sectional studies have consistently linked epigenetic age to health outcomes and lifespan.
• The current study extended this by examining whether the rate of change over time provides additional prognostic information.