Map of epigenetic age acceleration: A worldwide analysis

Area of Science:

• Epigenetics
• Genomics
• Population Health

Background:

• Epigenetic age acceleration is a biomarker for biological aging.
• Global variations in epigenetic age acceleration are not well understood.
• Existing epigenetic clocks have limitations in cross-tissue and cross-population applicability.

Purpose of the Study:

• To systematically analyze global epigenetic age acceleration using the largest public DNA methylation dataset.
• To evaluate the performance and consistency of popular epigenetic clocks across diverse geographic and ethnic groups.
• To investigate the influence of geography, ethnicity, and health status on epigenetic age acceleration.

Main Methods:

• Analysis of 93 public DNA methylation datasets (23K healthy samples) from 25 countries and 31 ethnicities.
• Utilized popular epigenetic clocks (PhenoAge, GrimAge, DunedinPACE) to assess age acceleration.
• Examined model quality metrics and extrapolation capabilities to different tissues and age ranges.

Main Results:

• Significant inconsistencies were observed among different epigenetic clock models.
• PhenoAge tended to underestimate, while GrimAge versions overestimated epigenetic age.
• DunedinPACE correlated with socioeconomic indicators but is limited to blood data.
• Males exhibited faster epigenetic aging than females across most populations.

Conclusions:

• Current epigenetic clocks show limitations in global application and consistency.
• Geographic, ethnic, and healthiness factors are challenging to disentangle due to data limitations.
• DunedinPACE shows promise for reflecting population-level health disparities.
• Sex-based differences in epigenetic aging are a consistent global finding.