Epigenetic Age Acceleration and Frailty Among People with HIV

Area of Science:

• Epigenetics and aging research
• HIV/AIDS and aging studies
• Gerontology and frailty research

Background:

• DNA methylation is a key indicator of biological aging.
• Epigenetic age acceleration (EAA) and frailty are common in people with HIV (PWH), but their relationship is poorly understood.
• Understanding EAA's role in frailty is crucial for developing targeted interventions for aging PWH.

Purpose of the Study:

• To investigate the association between EAA markers and frailty in people with HIV (PWH).
• To determine if EAA can predict frailty independently of traditional risk factors.
• To explore potential therapeutic targets for frailty in PWH based on EAA.

Main Methods:

• Observational study using data from the Veterans Aging Cohort Study (VACS).
• Epigenome-wide DNA methylation data analyzed using four epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge) to derive EAA markers.
• Frailty assessed using a validated VACS frailty-related phenotype; logistic regression used to test associations.

Main Results:

• Frailty was present in 36.9% of the 1,076 PWH studied.
• GrimAge acceleration (GrimAA), PhenoAge acceleration (PhenoAA), and HannumAge acceleration (HannumAA) were significantly associated with frailty.
• GrimAA was independently associated with a 45% increased odds of frailty (ORadj: 1.45) and showed a link with exercise frequency.

Conclusions:

• Select EAA markers, especially GrimAA, are associated with frailty in PWH, independent of conventional predictors.
• GrimAA may serve as a valuable biomarker for identifying PWH at higher risk of frailty.
• Future research can leverage GrimAA to develop personalized frailty management strategies for PWH.