Review: epigenetic clocks and accelerated biological aging in people living with HIV
This short review reports that first-generation epigenetic clocks generally estimate people living with HIV as about 5 to 7 years biologically older than HIV-negative people of similar chronological age, while noting that these clocks may be affected by HIV-related immune-cell changes. [1]
Automatic summary · not editorially reviewed
The key findings
The review states that many people living with HIV develop cardiovascular, metabolic, neurocognitive, musculoskeletal and frailty-related conditions earlier or more often than HIV-negative people of similar chronological age. [1]
First-generation clocks such as the Horvath and Hannum clocks generally indicate that people living with HIV are approximately 5 to 7 years biologically older than HIV-negative individuals of similar chronological age. [1]
Antiretroviral therapy may reduce epigenetic age acceleration but does not consistently restore biological age to the level observed in HIV-negative individuals. [1]
The source at a glance
- Study type / format
- Short review (abstract only)
- Population / context
- People living with HIV, compared with HIV-negative individuals of similar chronological age.
- Summary based on
- Study abstract
- Original publication
- September 12, 2026
HIV, earlier age-related conditions and clock aims
The review notes that combination antiretroviral therapy has greatly improved survival among people living with HIV. Still, many develop cardiovascular, metabolic, neurocognitive, musculoskeletal and frailty-related conditions earlier or more often than HIV-negative people of similar chronological age. DNA methylation-based epigenetic clocks estimate biological age and may help explain this burden. The review aims to summarize evidence on epigenetic age acceleration in people living with HIV, describe possible mechanisms, examine effects of antiretroviral therapy and sex-related factors, and discuss possible clinical uses.
Supporting source [1]
Clock estimates and proposed mechanisms in HIV
First-generation clocks, including the Horvath and Hannum clocks, generally indicate that people living with HIV are approximately 5 to 7 years biologically older than HIV-negative individuals of similar chronological age. However, these clocks may be affected by HIV-related changes in immune-cell composition. Newer measures, including PhenoAge, GrimAge, DunedinPACE, Retro-Age and immune-composition-resistant clocks, assess different aspects such as physiological decline, mortality risk, pace of aging and retroelement-associated methylation. HIV-associated epigenetic aging appears to involve persistent viral activity, chronic immune activation, inflammation, immunosenescence, mitochondrial dysfunction, oxidative stress, altered one-carbon metabolism, glutathione deficiency, cellular senescence and treatment-related metabolic or mitochondrial effects.
Supporting source [1]
Therapy, sex factors and validation needs
Antiretroviral therapy may reduce epigenetic age acceleration, but it does not consistently restore biological age to the level seen in HIV-negative individuals. Sex, menopause, metabolic dysfunction and body composition may also influence the relationship between epigenetic aging, frailty and mortality. The review concludes that epigenetic clocks may improve assessment of biological aging in people living with HIV and could support risk stratification, early identification of frailty and evaluation of interventions. However, longitudinal validation, standardized methods, adjustment for immune-cell composition and evidence linking clock changes with meaningful clinical outcomes are required before routine use in HIV care.
Supporting source [1]
How to interpret this
This explainer is based only on the abstract; the full text was not reviewed. The source is a short review, not a new longitudinal study, and it reports no sample sizes, follow-up periods or outcome data. The 5-to-7-year estimates come from first-generation clocks that may be affected by immune-cell composition. The review itself states that longitudinal validation, standardized methods, adjustment for immune-cell composition and evidence linking clock changes to meaningful clinical outcomes are still required. Associations described are not established causes.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Chan ASW. · europepmc.org · September 12, 2026