DNA methylation-based epigenetic clocks highlight immune-driven aging acceleration in COVID-19 across diverse populations

COVID-19 patients exhibited accelerated epigenetic aging as measured by DNA methylation markers, particularly in older and female individuals.

• PCGrimAge, an advanced epigenetic clock, correlated strongly with chronological age in European COVID-19 patients.
• Other epigenetic clocks, including DunedinPACE and ZhangY2017, also indicated accelerated aging in older and female patients.
• First-generation clocks like Hannum2013 suggested a significant reduction in epigenetic aging, likely due to their limited sensitivity to infection-related changes.
• Immune dysregulation, rather than intrinsic cellular aging, may primarily drive accelerated epigenetic aging in COVID-19 patients.
• Stronger associations were found with Age Acceleration and Extrinsic Epigenetic Age Acceleration compared to Intrinsic Epigenetic Age Acceleration.
• Significant differences were noted between European and non-European populations, with higher intrinsic aging markers in non-European COVID-19 patients.

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