Associations between psychosocial and lifestyle factors and biological age acceleration among long-term survivors of childhood cancer: A prospective study from the St. Jude Lifetime Cohort

10049 Background: Survivors of childhood cancers may be at risk for premature, or accelerated, biological age aging, which is associated with cancer treatment exposures. However, life course theory and a growing body of evidence suggest that psychosocial and lifestyle factors may also contribute. The objective of this study was to explore associations between psychosocial and lifestyle factors and biological age acceleration in the St. Jude Lifetime Cohort. Methods: In this cross-sectional study, we applied physiology-based methods (Klemera-Doubal method and Phenotypic Age) and DNA methylation-based epigenetic clocks (Horvath’s, Hannum’s, Levine’s PhenoAge, GrimAge, and DunedinPACE clocks) to compare biological age acceleration, estimated as the residual from regressing biological age on chronological age, among survivors (n = 4,117) and age- and sex-frequency-matched non-cancer community controls (n = 606). We compared psychosocial and lifestyle factors between survivors and controls using t-tests/Wilcoxan rank sums, and chi-square. Multivariable linear regression was used to assess associations of self-reported smoking, alcohol use, physical activity, overweight/obesity, and depressive symptoms with biological age acceleration in survivors, adjusted for age, race/ethnicity, sex, education, and cancer treatment. Results: Childhood cancer survivors at a mean chronological age of 35.1 years (SD 10.2) were biologically older than controls according to KDM-BA, Phenotypic Age, Hannum’s clock, Levine’s PhenoAge clock, and DunedinPACE, with biological age acceleration ranging from 1.7-4.7 years (p < 0.05.) A greater proportion of survivors reported elevated depressive symptoms (10.3% v. 8.7%), current smoking (17.8% v. 12.3%), < 150 minutes of physical activity (47.3% v. 38.2%), and were overweight/obese (66.0% v. 59.9%) compared to controls (p’s < 0.001). In survivors, < 150 minutes of physical activity (B’s (difference in biological age acceleration [years]) = 1.10-2.68), current (B’s = 1.18-5.96) and former smoking (B’s = 2.53-4.29) were consistently associated with higher biological age acceleration across measures (p’s < 0.05). Risky drinking and higher depressive symptoms were associated with higher biological age acceleration, but only for KDM (B = 1.26, p < 0.021) and DunedinPACE measures (B = 0.15, p < 0.001), respectively. Conclusions: Biological aging in childhood cancer survivors is associated with psychosocial and lifestyle factors. Interventions designed to optimize healthy behaviors and mitigate poor emotional health may have potential to prevent or remediate this phenotype in childhood cancer survivors.