Sex differences in epigenetic ageing for older people living with HIV

作者：Carrie D. Johnston, Alina P.S. Pang, Eugenia L. Siegler, Charlene Thomas, Chelsie O. Burchett, Mia Crowley, Rochelle O’Brien, Lishomwa C. Ndhlovu, Marshall J. Glesby, Michael J. Corley · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2025.105588 · 被引用次数：9 · 研究领域：Epigenetics and DNA Methylation、HIV-related health complications and treatments、HIV Research and Treatment

BACKGROUND: HIV-1 infection impacts biological ageing, and epigenetic clocks highlight epigenetic age acceleration in people with HIV. Despite evidence indicating sex differences in clinical, immunological, and virological measures, females have been underrepresented in most HIV epigenetic studies. Hence, we generated a more representative epigenetic dataset to examine sex differences in epigenetic ageing and relationships to clinical phenotypes and proteomics. METHODS: We calculated first, second, and third-generation epigenetic ages using DNA methylation data in an observational cohort of 52 females and 106 males with HIV age 50 and over. We profiled plasma biomarkers with Olink high-throughput proteomics to test associations with epigenetic age acceleration. Survival was ascertained over 5 years. FINDINGS: Epigenetic age acceleration measured by three principal-component based chronological epigenetic age clocks (p = 0.0029, 0.021, 0.010) and one epigenetic mortality risk clock was significantly lower in females living with HIV compared to males (p = 0.0011). Additionally, sex was significantly associated with epigenetic biomarker scores for proportion of naïve CD4+ T cells (p = 0.0006), physical fitness including DNAmGait (p = 0.0010), DNAmGrip (p < 0.0001), and DNAmV02 max (p < 0.0001). We found epigenetic age acceleration associated with plasma proteomic markers involved in inflammation, senescence, immune regulation, kidney function, and tissue homoeostasis (p < 0.0001...