Cell-type specific impact of metformin on monocyte epigenetic age reversal in virally suppressed older people living with HIV.
Level 2 - randomized trial
Secondary analysis of biological samples from a randomized controlled trial and a single-arm trial
PubMed 37675817 · doi:10.1111/acel.13926
What was done
Researchers retrospectively measured epigenetic age using principal component (PC)-based epigenetic clocks, mitotic clocks, and pace of aging in isolated peripheral monocytes and CD8+ T cells from normoglycemic, virologically suppressed people living with HIV across two clinical studies. The first was a 24-week randomized trial comparing adjunctive metformin to an observation control group. The second was a single-arm trial evaluating adjunctive metformin in 8 participants with assessments at baseline, 4 weeks, and 8 weeks.
What was found
In the randomized trial, participants receiving metformin showed significant reductions in monocyte epigenetic age from baseline to week 24, with PCPhenoAge decreasing by a mean of 3.53 years and PCGrimAge decreasing by a mean of 1.84 years, whereas the observation arm showed no significant changes across PC clocks. Monocyte epigenetic mitotic clocks significantly increased in the metformin group over 24 weeks. In the single-arm study (n = 8), metformin produced no significant changes across any epigenetic clocks assessed in CD8+ T cells at 4 or 8 weeks.
Why it matters
This study provides proof-of-concept human data that metformin may exert cell-type-specific effects on biological aging markers in monocytes among individuals with treated HIV.
Limits
The randomized trial sample size is described only as small without a specific count in the abstract, the single-arm trial included only 8 participants, the analysis was retrospective, and the control group in the 24-week trial was unblinded observation rather than a placebo.
Cited by
- supports Studies suggest metformin affects epigenetic age, though its effect is much weaker than antiretroviral or anti-TNF therapies.