ArticleJournal of cachexia, sarcopenia and muscle2023
Gene polymorphisms associated with heterogeneity and senescence characteristics of sarcopenia in chronic obstructive pulmonary disease.
Article in Journal of cachexia, sarcopenia and muscle, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 14 citations in OpenAlex.
- Attenuated FTO induces necroptosis of alveolar epithelium via the mRedox biology · 2026Article
- Integrative GWAS Catalog Analysis of Proxy-Trait Intersection in Sarcopenia-Related Musculoskeletal Aging with Multi-Criteria Evidence Integration.Life (Basel, Switzerland) · 2026Article
- Mitochondrial and Epigenetic Drivers of Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease.Antioxidants (Basel, Switzerland) · 2026Review
- Pathological changes and therapeutic strategies for sarcopenia.EFORT open reviews · 2026Review
- Development and validation of a clinical nomogram for frailty prediction in older COPD patients: a machine learning approach.BMC geriatrics · 2026Article
- From Weight Loss to Standardized Sarcopenia Assessment: A Multi-Database Bibliometric Study of COPD with Sarcopenia (2005-2025).International journal of chronic obstructive pulmonary disease · 2026Article
- The lung-muscle axis in COPD: a conceptual framework integrating evidence, mechanisms, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Body composition in stable COPD: associations with disease severity and early sarcopenia prediction.Frontiers in nutrition · 2026Article
- FTO Suppresses Dental Pulp Stem Cell Senescence by DestabilizingBiomolecules · 2025Article
- Decoding LncRNA in COPD: Unveiling Prognostic and Diagnostic Power and Their Driving Role in Lung Cancer Progression.International journal of molecular sciences · 2024Review
- Sarcopenia as a Risk Factor for Alzheimer's Disease: Genetic and Epigenetic Perspectives.Genes · 2024Review
- Muscle loss phenotype in COPD is associated with adverse outcomes in the UK Biobank.BMC pulmonary medicine · 2024Article
- Higher ultra processed foods intake is associated with low muscle mass in young to middle-aged adults: a cross-sectional NHANES study.Frontiers in nutrition · 2024Article
- Gene polymorphisms associated with heterogeneity and senescence characteristics of sarcopenia in chronic obstructive pulmonary disease.Journal of cachexia, sarcopenia and muscle · 2023Article
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundSarcopenia, or loss of skeletal muscle mass and decreased contractile strength, contributes to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). The severity of sarcopenia in COPD is variable, and there are limited data to explain phenotype heterogeneity. Others have shown that COPD patients with sarcopenia have several hallmarks of cellular senescence, a potential mechanism of primary (age-related) sarcopenia. We tested if genetic contributors explain the variability in sarcopenic phenotype and accelerated senescence in COPD.
methodsTo identify gene variants [single nucleotide polymorphisms (SNPs)] associated with sarcopenia in COPD, we performed a genome-wide association study (GWAS) of fat free mass index (FFMI) in 32 426 non-Hispanic White (NHW) UK Biobank participants with COPD. Several SNPs within the fat mass and obesity-associated (FTO) gene were associated with sarcopenia that were validated in an independent COPDGene cohort (n = 3656). Leucocyte telomere length quantified in the UK Biobank cohort was used as a marker of senescence. Experimental validation was done by genetic depletion of FTO in murine skeletal myotubes exposed to prolonged intermittent hypoxia or chronic hypoxia because hypoxia contributes to sarcopenia in COPD. Molecular biomarkers for senescence were also quantified with FTO depletion in murine myotubes.
resultsMultiple SNPs located in the FTO gene were associated with sarcopenia in addition to novel SNPs both within and in proximity to the gene AC090771.2, which transcribes long non-coding RNA (lncRNA). To replicate our findings, we performed a GWAS of FFMI in NHW subjects from COPDGene. The SNP most significantly associated with FFMI was on chromosome (chr) 16, rs1558902A > T in the FTO gene (β = 0.151, SE = 0.021, P = 1.40 × 10
conclusionsGenetic polymorphisms of FTO and AC090771.2 were associated with sarcopenia in COPD in independent cohorts. Knockdown of FTO in murine myotubes caused a molecular phenotype consistent with senescence that was exacerbated by hypoxia, a common condition in COPD. Genetic variation may interact with hypoxia and contribute to variable severity of sarcopenia and skeletal muscle molecular senescence phenotype in COPD.
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