BiogerontologyDec 2, 2025

Epigenetic clocks based on DNA methylation show faster immune-related aging in COVID-19 across different populations

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

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.

Simplified

The SARS-CoV-2 pandemic has affected millions worldwide, with aging being a key risk factor for severe disease outcomes. This study examines the rate of epigenetic aging, as measured by DNA methylation-based aging markers, in COVID-19 patients versus healthy individuals. We found that PCGrimAge, a next-generation epigenetic clock associated with immune dysregulation and inflammation, showed the strongest correlation with the chronological age of the European COVID-19 patients. Several other next-generation epigenetic clocks, including PCGrimAge, DunedinPACE, and ZhangY2017, also exhibited accelerated aging in both older and female COVID-19 patients. Interestingly, first-generation clocks, such as Hannum2013, indicated a significant reduction in epigenetic aging, likely reflecting limitations in their sensitivity to infection-related biological changes rather than an actual deceleration of the aging process. Our results also showed that immune dysregulation, rather than intrinsic cellular aging, may be the primary driver of accelerated epigenetic aging in COVID-19. This is supported by stronger associations observed in Age Acceleration (AA) and Extrinsic Epigenetic Age Acceleration (EEAA) compared to Intrinsic Epigenetic Age Acceleration (IEAA). Furthermore, immune dysregulation may be linked to CpG site demethylation, which in turn influences epigenetic clock dynamics. We also identified disparities between European and non-European populations, characterized by significantly higher IEAA for PCPhenoAge and DunedinPACE among non-European patients with COVID-19. In summary, our results underscore the differential sensitivity of epigenetic clocks to COVID-19-related biological changes.

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Competing interests

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: This article involves only computational work and contains no studies with human participants or animals.

PubMed

Epigenetic clocks based on DNA methylation show faster immune-related aging in COVID-19 across different populations

Abstract

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