Association of Epigenetic Age Acceleration and Mitochondrial DNA-Based Aging Metrics Provides Insights Into Mechanisms of Aging-Related Diseases.

ABSTRACT: Investigating the interplay between mitochondrial DNA (mtDNA) variations and epigenetic aging metrics may elucidate biological mechanisms associated with age-related diseases. We estimated epigenetic age acceleration (EAA) metrics from DNA methylation data and derived mtDNA metrics, including heteroplasmic variants and mtDNA copy number (mtDNA CN) from whole genome sequencing. Linear regressions and meta-analyses were conducted to assess associations between EAA and mtDNA metrics, adjusting for chronological age, self-identified sex, and other covariates in 6,316 participants (58% female, 41% non-White Americans). Mediation analysis was conducted to examine whether EAA mediated the relationship between mtDNA CN and metabolic traits. A higher burden of rare heteroplasmic variants was associ

SUBMITTER: Wang M 

PROVIDER: S-EPMC12686565 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature