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Epigenetic aging biomarkers associated with cognitive impairment in older African American adults with HIV.

BACKGROUND
Accelerated epigenetic aging using DNA methylation (DNAm)-based biomarkers has been reported in people with HIV (PWH), but limited data are available among African Americans (AA), women, and older PWH.


METHODS
DNAm was measured using Illumina EPIC Arrays for 107 (69 PWH and 38 HIV-seronegative controls) AA adults ≥60 years in New York City. Six DNAm-based biomarkers of aging were estimated: (1) epigenetic age acceleration (EAA), (2) extrinsic epigenetic age acceleration (EEAA), (3) intrinsic epigenetic age acceleration (IEAA), (4) GrimAge, (5) PhenoAge, and (6) DNAm-estimated telomere length (DNAm-TL). The NIH Toolbox Cognition Battery (domains: executive function, attention, working memory, processing speed, and language) and Montreal Cognitive Assessment (MoCA) were administered. Participants were assessed for frailty by the Fried criteria.


RESULTS
The PWH and control groups did not differ by sex, chronological age, or ethnicity. 83% of PWH had a viral load <50 copies/mL and 94% had a recent CD4 ≥200 cells/µL. The PWH group had a higher EAA, EEAA, GrimAge, and PhenoAge, and a lower DNAm-TL compared to the controls. IEAA was not different between groups. For PWH, there were significant negative correlations between IEAA and executive function, attention, and working memory and PhenoAge and attention. No associations between biomarkers and frailty were detected.


CONCLUSION
Evidence of epigenetic age acceleration was observed in AA older PWH using DNAm-based biomarkers of aging. There was no evidence of age acceleration independent of cell type composition (IEAA) associated with HIV, but this measure was associated with decreased cognitive function among PWH.