Epigenetic clocks and their association with trajectories in perceived discrimination and depressive symptoms among US middle-aged and older adults

Background: Perceived discrimination may be associated with accelerated aging later in life, with depressive symptoms acting as potential mediator. Methods: A nationally representative sample of older adults was used [Health and Retirement Study 2010-2016, Age: 50-100 y in 2016, N = 2,806, 55.6% female, 82.3% Non-Hispanic White (NHW)] to evaluate associations of perceived discrimination measures [Experience of discrimination or EOD; and Reasons for Perceived discrimination or RPD) and depressive symptoms (DEP)] with 13 DNAm-based measures of epigenetic aging. Group-based trajectory and four-way mediation analyses were used. Results: Overall, and mostly among female and NHW participants, greater RPD in 2010-2012 had a significant adverse total effect on epigenetic aging [2016: DNAm GrimAge, DunedinPoAm38 (MPOA), Levine (PhenoAge) and Horvath 2], with 20-50% of this effect being explained by a pure indirect effect through DEP in 2014-2016. Among females, sustained elevated DEP (2010-2016) was associated with greater LIN DNAm age (beta +/- SE: +1.506 +/- 0.559, p = 0.009, reduced model), patterns observed for elevated DEP (high vs. low) for GrimAge and MPOA DNAm markers. Overall and in White adults, the relationship of the Levine clock with perceived discrimination in general (both EOD and RPD) was mediated through elevated DEP. Conclusions: Sustained elevations in DEP and RPD were associated with select biological aging measures, consistently among women and White adults, with DEP acting as mediator in several RPD-EPICLOCK associations.