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. 2024 Jan;23(1):e14025.
doi: 10.1111/acel.14025. Epub 2023 Nov 3.

Skeletal muscle DNA methylation: Effects of exercise and HIV

Catherine M Jankowski  1 , Iain R Konigsberg  2 , Melissa P Wilson  3 , Jing Sun  4 , Todd T Brown  5 , Colleen G Julian  2 , Kristine M Erlandson  3   6
Affiliations

Skeletal muscle DNA methylation: Effects of exercise and HIV

Catherine M Jankowski et al. Aging Cell. 2024 Jan.

Abstract

Aging, human immunodeficiency virus (HIV) infection, and antiretroviral therapy modify the epigenetic profile and function of cells and tissues, including skeletal muscle (SkM). In some cells, accelerated epigenetic aging begins very soon after the initial HIV infection, potentially setting the stage for the early onset of frailty. Exercise imparts epigenetic modifications in SkM that may underpin some health benefits, including delayed frailty, in people living with HIV (PWH). In this first report of exercise-related changes in SkM DNA methylation among PWH, we investigated the impact of 24 weeks of aerobic and resistance exercise training on SkM (vastus lateralis) DNA methylation profiles and epigenetic age acceleration (EAA) in older, virally suppressed PWH (n = 12) and uninfected controls (n = 18), and associations of EAA with physical function at baseline. We identified 983 differentially methylated positions (DMPs) in PWH and controls at baseline and 237 DMPs after training. The influence of HIV serostatus on SkM methylation was more pronounced than that of exercise training. There was little overlap in the genes associated with the probes most significantly differentiated by exercise training within each group. Baseline EAA (mean ± SD) was similar between PWH (-0.4 ± 2.5 years) and controls (0.2 ± 2.6 years), and the exercise effect was not significant (p = 0.79). EAA and physical function at baseline were not significantly correlated (all p ≥ 0.10). This preliminary investigation suggests HIV-specific epigenetic adaptations in SkM with exercise training but confirmation in a larger study that includes transcriptomic analysis is warranted.

Keywords: DNA methylation; HIV; aging; epigenetic; epigenetic clock; exercise training; skeletal muscle.

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Conflict of interest statement

The authors have not and do not currently have a commercial or other association that might pose of conflict of interest with the research.

Figures

FIGURE 1
FIGURE 1
Exercise for healthy aging epigenetic sub‐study overview. PWH, people with HIV.
FIGURE 2
FIGURE 2
Volcano plots of differentially methylated CpG sites in skeletal muscle of people with HIV (PWH) and controls at (a) pre‐training (i.e., baseline) and (b) post‐training. Significant differentiation, gray; nonsignificant, black. FDR, false discovery rate.
FIGURE 3
FIGURE 3
Principal component analysis (PCA) plots of SkM DNA methylation (DNAm) for people with (PWH) and uninfected controls pre‐ and postexercise training. The PCA plots show distinct clustering by HIV serostatus and minimal clustering by exercise training. Each dot represents a unique individual. PWH are designated by red (baseline) or purple (postexercise training) dots. Uninfected controls are designated by blue (baseline) or green (postexercise training) dots. Enlarged points represent the median centroid for each group.
FIGURE 4
FIGURE 4
Skeletal muscle epigenetic age acceleration (SkM EAA) pre‐ and postexercise training in PWH (n = 12) and controls (n = 18). The dotted line represents the mean chronological age (pre‐training). SkM EAA estimated using the MEAT V2.0 epigenetic clock (Voisin et al., 2021). Pre‐training comparison, p = 0.50; post‐training comparison, p = 0.79).
See this image and copyright information in PMC

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