Epigenetic Aging and Musculoskeletal Outcomes in a Cohort of Women Living With HIV

Background. The relationship between accelerated epigenetic aging and musculoskeletal outcomes in women with HIV (WWH) has not been studied. Methods. We measured DNA methylation age using the Infinium MethylationEPIC BeadChip in a cohort from the Women’s Interagency HIV Study (n = 190) with measures of bone mineral density (BMD) and physical function. We estimated 6 biomarkers of epigenetic aging—epigenetic age acceleration (EAA), extrinsic EAA, intrinsic EAA, GrimAge, PhenoAge, and DNA methylation–estimated telomere length—and evaluated associations of epigenetic aging measures with BMD and physical function. We also performed epigenome-wide association studies to examine associations of DNA methylation signatures with BMD and physical function. Results. This study included 118 WWH (mean age, 49.7 years; 69% Black) and 72 without HIV (mean age, 48.9 years; 69% Black). WWH had higher EAA (mean ± SD, 1.44 ± 5.36 vs −1.88 ± 5.07; P < .001) and lower DNA methylation–estimated telomere length (7.13 ± 0.31 vs 7.34 ± 0.23, P < .001) than women without HIV. There were no significant associations between accelerated epigenetic aging and BMD. Rather, measures of accelerated epigenetic aging were associated with lower physical function. Conclusions. Accelerated epigenetic aging was observed in WWH as compared with women without HIV and was associated with lower physical function in both groups.