Longitudinal changes in epigenetic clocks predict survival in the InCHIANTI cohort

Area of Science:

• Biochemistry
• Genetics
• Gerontology

Background:

• Epigenetic clocks using DNA methylation are key biomarkers of biological aging.
• Previous studies linked cross-sectional epigenetic age to health outcomes and lifespan.
• The prognostic value of temporal changes in epigenetic clocks for mortality is not well understood.

Purpose of the Study:

• To investigate the association between the rate of change in epigenetic clocks and mortality risk.
• To determine if temporal acceleration of epigenetic clocks provides additional predictive information beyond baseline age.

Main Methods:

• Longitudinal study of 699 adults from the InCHIANTI cohort over up to 24 years.
• Evaluation of temporal acceleration in first-, second-, and third-generation epigenetic clocks.
• Statistical analysis accounting for baseline epigenetic age and other confounders.

Main Results:

• Faster increases in several epigenetic clocks were robustly associated with an increased risk of death.
• This association remained significant independent of baseline epigenetic age and other risk factors.
• Dynamic changes in epigenetic aging appear to reflect evolving health status.

Conclusions:

• Temporal acceleration of epigenetic clocks is a significant predictor of mortality.
• Monitoring changes in epigenetic age may offer insights into health trajectories.
• These findings support the potential of epigenetic clocks for interventions targeting healthspan and longevity.