The pace of biological aging varies between people independently of chronological age and mitochondria dysfunction is a key hallmark of biological aging. We hypothesized that higher functional impact (FI) score of mitochondrial DNA (mtDNA) variants might contribute to premature aging and tested the relationships between a novel FI score of mtDNA variants and epigenetic and biological aging in young adulthood. A total of 81 participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort had good quality genetic data as well as blood-based markers to estimate biological aging in the late 20. A subset of these participants (n = 69) also had epigenetic data to estimate epigenetic aging in the early 20s using Horvath's epigenetic clock. The novel FI score was calculated based on 7 potentially pathogenic mtDNA variants. Greater FI score of mtDNA variants was associated with older epigenetic age in the early 20s and older biological age in the late 20s. These medium to large effects were independent of sex, current BMI, cigarette smoking, cannabis, and alcohol use. These findings suggest that elevated FI score of mtDNA variants might contribute to premature aging in young adulthood.

1st Department of Neurology St Anne's University Hospital and Faculty of Medicine Masaryk University Brno Czech Republic

Brain and Mind Research Central European Institute of Technology Masaryk University Brno Czech Republic

Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health Toronto ON Canada

Department of Psychiatry University of Saskatchewan Saskatoon SK Canada

Department of Psychiatry University of Toronto Toronto ON Canada

Faculty of Informatics Masaryk University Brno Czechia

RECETOX Faculty of Science Masaryk Univeristy Brno Czech Republic

Tanenbaum Centre for Pharmacogenetics Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health Toronto ON Canada

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