AbstractBackgroundYoung adult cancer survivors experience early aging‐related morbidities and mortality. Biological aging biomarkers may identify at‐risk survivors and increase our understanding of mechanisms underlying this accelerated aging.MethodsUsing an observational study design, we cross‐sectionally measured DNA methylation‐based epigenetic age in young adult cancer survivors at a tertiary, academic state cancer hospital. Participants were a convenience sample of consecutively enrolled survivors of childhood, adolescent, and young adult cancers treated with either an anthracycline or alkylating agent, and who were at least 3 months post‐treatment. Similarly aged healthy comparators were consecutively enrolled. Cancer treatment and treatment intensity were compared to DNA methylation‐based epigenetic age and pace of aging.ResultsSixty survivors (58 completing assessments, mean age 20.5 years, range 18–29) and 27 comparators (mean age 20 years, range 17–29) underwent DNA methylation measurement. Survivors were predominantly female (62%) and white (60%) and averaged nearly 6 years post‐treatment (range 0.2–25 years). Both epigenetic age (AgeAccelGrim: 1.5 vs. −2.4,p< 0.0001; AgeAccelPheno 2.3 vs. −3.8,p= 0.0013) and pace of aging (DunedinPACE 0.99 vs. 0.83,p< 0.0001) were greater in survivors versus comparators. In case–case adjusted analysis, compared to survivors with normal muscle mass, myopenic survivors had higher AgeAccelGrim (2.2 years, 95% CI 0.02–4.33,p= 0.02), AgeAccelPheno (6.2 years, 2.36–10.09,p< 0.001), and DunedinPACE (0.11, 0.05–0.17,p< 0.001).ConclusionsEpigenetic age is older and pace of aging is faster in young adult cancer survivors compared to noncancer peers, which is evident in the early post‐therapy period. Survivors with physiological impairment demonstrate greater epigenetic age advancement. Measures of epigenetic age may identify young adult survivors at higher risk for poor functional and health outcomes.