ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2026
Epigenetic Modulation of the ACE System Underlies the Slow Aerobic Muscle Phenotype and Metabolic Exercise Response.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Epigenetic regulation of the angiotensin-converting enzyme (ACE)-particularly CpG methylation within its promoter-may modulate gene expression and skeletal muscle adaptation to endurance exercise, complementing the known effects of the ACE I/D polymorphism (rs1799752). We hypothesized that ACE promoter methylation correlates with markers of aerobic metabolism and interacts with genotype and enzyme activity to explain interindividual variability in muscle oxidative capacity. 114 samples from healthy, physically diverse white Caucasian men (age: 29.5 ± 8.1 years; weight: 76.9 ± 14.5 kg) were analyzed for aerobic capacity, metabolic profiles and cellular composition of m. vastus lateralis. Molecular endpoints of the ACE system included ACE genotype, promoter methylation (23 CpG sites), mRNA expression, enzyme activity, angiotensin 2 levels, and markers of mitochondrial, glycolytic, and lipid metabolism. ACE promoter methylation in muscle was compared to the methylation in capillary blood from a second study group of 24 VO2max- and genotype-matched male white Caucasian subjects. Statistical analyses comprised Pearson correlations, regression modeling (α = 0.05), network analysis, and ANOVA. Participants exhibited a wide range in VO₂max (2.1-5.4 L·min
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