College of Nursing, University of Colorado Anschutz Medical Campus, Colorado, Aurora, USA.
Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Colorado, Aurora, USA.
Aging Cell. 2024 Jan;23(1):e14025. doi: 10.1111/acel.14025. Epub 2023 Nov 3.
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.
衰老、人类免疫缺陷病毒（HIV）感染和抗逆转录病毒治疗会改变细胞和组织的表观遗传特征和功能，包括骨骼肌（SkM）。在某些细胞中，HIV 感染后最初阶段，表观遗传衰老就会加速，这可能为虚弱的早期发生奠定基础。运动可使 SkM 产生表观遗传修饰，这可能是 HIV 感染者（PWH）健康获益的基础，包括延迟虚弱。在这项关于 PWH 骨骼肌 DNA 甲基化与运动相关变化的首次报告中，我们研究了 24 周有氧运动和抗阻运动训练对衰老、病毒抑制的 PWH（n=12）和未感染对照者（n=18）SkM（股外侧肌）DNA 甲基化谱和表观遗传年龄加速（EAA）的影响，以及 EAA 与基线身体功能的相关性。我们在 PWH 和对照组中发现了 983 个在基线时有差异的甲基化位置（DMP）和 237 个在训练后有差异的 DMP。HIV 血清状态对 SkM 甲基化的影响比运动训练更显著。在每组中，与训练后差异最显著的探针相关的基因之间几乎没有重叠。PWH 的 EAA 基线值（均值±标准差）与对照组相似（分别为-0.4±2.5 岁和 0.2±2.6 岁），且运动训练的影响不显著（p=0.79）。EAA 和基线时的身体功能无显著相关性（所有 p 值均≥0.10）。这项初步研究表明，运动训练可使 SkM 产生 HIV 特异性的表观遗传适应，但需要更大规模的研究来证实，该研究还需包含转录组分析。
