ArticleJournal of cachexia, sarcopenia and muscle2022
Epigenome-wide association study of sarcopenia: findings from the Hertfordshire Sarcopenia Study (HSS).
Article in Journal of cachexia, sarcopenia and muscle, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Association of muscle mass and strength with blood-based epigenetic aging among middle-aged and older adults in the United States.GeroScience · 2026Article
- Epigenetic Aging of Critical Illness Survivors Assessed by the Muscle-Specific "Clock" and Its Relationship With Reduced Long-Term Muscle Strength.Aging cell · 2026Article
- Single-Cell RNAseq Identifies Heterogeneity in Myoblasts From Older Adults With Differences Related to Muscle Mass and Function.Journal of cachexia, sarcopenia and muscle · 2026Article
- Malnutrition-Sarcopenia Syndrome in older adults: Causes, consequences, and countermeasures.EXCLI journal · 2026Review
- Insights into WDR5: unveiling its functions, regulation, and impact on skeletal muscle.Epigenetics · 2025Review
- Article
- Neural Cues and Genomic Clues: NGS Insights into Neurogenic Sarcopenia and Muscle Atrophy.International journal of molecular sciences · 2025Review
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- The skeletal muscle proteomic determinants of neuromuscular function in young and older women following 8 weeks of resistance training.Experimental physiology · 2025Article
- Exploration of Pathogenesis and Cutting-Edge Treatment Strategies of Sarcopenia: A Narrative Review.Clinical interventions in aging · 2025Review
- Dietary polyphenols and sarcopenia: epigenetic mechanisms and geroscience perspectives for muscle health in aging.Frontiers in aging · 2025Review
- Age-related histone H3.3 accumulation associates with a repressive chromatin in mouse tibialis anterior muscle.The journal of physiological sciences : JPS · 2024Article
- DNA methylation of skeletal muscle function-related secretary factors identifies FGF2 as a potential biomarker for sarcopenia.Journal of cachexia, sarcopenia and muscle · 2024Article
- Sarcopenic obesity in older adults: a clinical overview.Nature reviews. Endocrinology · 2024Review
- Trigonelline is an NADNature metabolism · 2024Article
- Research Progress on the Effect and Mechanism of Exercise Intervention on Sarcopenia Obesity.Clinical interventions in aging · 2024Review
- Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twins.Frontiers in cell and developmental biology · 2024Article
- Skeletal muscle DNA methylation: Effects of exercise and HIV.Aging cell · 2024Article
- Effects of household solid fuel use on sarcopenia in middle-aged and older adults: evidence from a nationwide cohort study.Frontiers in public health · 2024Article
- Hallmarks of ageing in human skeletal muscle and implications for understanding the pathophysiology of sarcopenia in women and men.Clinical science (London, England : 1979) · 2023Article
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Authors and funding
23 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundSarcopenia is the age-related loss of muscle mass, strength, and function. Epigenetic processes such as DNA methylation, which integrate both genetic and environmental exposures, have been suggested to contribute to the development of sarcopenia. This study aimed to determine whether differences in the muscle methylome are associated with sarcopenia and its component measures: grip strength, appendicular lean mass index (ALMi), and gait speed.
methodsUsing the Infinium Human MethylationEPIC BeadChip, we measured DNA methylation in vastus lateralis muscle biopsies of 83 male participants (12 with sarcopenia) with a mean (standard deviation) age of 75.7 (3.6) years from the Hertfordshire Sarcopenia Study (HSS) and Hertfordshire Sarcopenia Study extension (HSSe) and examined associations with sarcopenia and its components. Pathway, histone mark, and transcription factor enrichment of the differentially methylated CpGs (dmCpGs) were determined, and sodium bisulfite pyrosequencing was used to validate the sarcopenia-associated dmCpGs. Human primary myoblasts (n = 6) isolated from vastus lateralis muscle biopsies from male individuals from HSSe were treated with the EZH2 inhibitor GSK343 to assess how perturbations in epigenetic processes may impact myoblast differentiation and fusion, measured by PAX7 and MYHC immunocytochemistry, and mitochondrial bioenergetics determined using the Seahorse XF96.
resultsSarcopenia was associated with differential methylation at 176 dmCpGs (false discovery rate ≤ 0.05) and 141 differentially methylated regions (Stouffer ≤ 0.05). The sarcopenia-associated dmCpGs were enriched in genes associated with myotube fusion (P = 1.40E-03), oxidative phosphorylation (P = 2.78E-02), and voltage-gated calcium channels (P = 1.59E-04). ALMi was associated with 71 dmCpGs, grip strength with 49 dmCpGs, and gait speed with 23 dmCpGs (false discovery rate ≤ 0.05). There was significant overlap between the dmCpGs associated with sarcopenia and ALMi (P = 3.4E-35), sarcopenia and gait speed (P = 4.78E-03), and sarcopenia and grip strength (P = 7.55E-06). There was also an over-representation of the sarcopenia, ALMi, grip strength, and gait speed-associated dmCpGs with sites of H3K27 trimethylation (all P ≤ 0.05) and amongst EZH2 target genes (all P ≤ 0.05). Furthermore, treatment of human primary myoblasts with the EZH2 inhibitor GSK343 inhibitor led to an increase in PAX7 expression (P ≤ 0.05), decreased myotube fusion (P = 0.043), and an increase in ATP production (P = 0.008), with alterations in the DNA methylation of genes involved in oxidative phosphorylation and myogenesis.
conclusionsThese findings show that differences in the muscle methylome are associated with sarcopenia and individual measures of muscle mass, strength, and function in older individuals. This suggests that changes in the epigenetic regulation of genes may contribute to impaired muscle function in later life.
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