{"title":"A multi-omics investigation of sarcopenia and frailty: Integrating genomic, epigenomic and telomere length data.","authors":"Valentina Ginevičienė, Erinija Pranckevičienė, Alina Urnikytė, Laura Jurkūnaitė, Kristijona Gutauskaitė, Rūta Dadelienė, Justina Kilaitė, Ieva Eglė Jamontaitė, Asta Mastavičiūtė, Ildus I Ahmetov, Vidmantas Alekna","doi":"10.1113/EP092853","DOIUrl":null,"url":null,"abstract":"<p><p>Sarcopenia and frailty are complex geriatric syndromes influenced by a combination of genetic and environmental factors. Recent studies suggest that specific genetic variants, DNA methylation patterns and shortened telomeres are associated with age-related diseases and might contribute to the development of both sarcopenia and frailty. In this study, we investigated the contribution of multi-omics data to sarcopenia, frailty, lean mass index (LMI) and handgrip strength in an elderly Lithuanian population. A total of 204 participants (age 82.2 ± 7.6 years) were included, comprising 122 individuals diagnosed with sarcopenia and/or frailty and 82 healthy, community-dwelling older adults. The results showed that LMI was associated with various health and lifestyle factors. Two genetic variants, CLIC5 rs75652203 and GHITM rs17102732, were found to be significantly associated with handgrip strength at the genome-wide level. Additionally, 12 polymorphisms previously linked to sarcopenia were replicated in relationship to LMI: BOK rs76993203, VAMP5 rs1374370, TMEM18 rs12714414, SFMBT1 rs36033494, BANK1 rs13136118, TET2 rs2647239, FOXO3 rs9384679, L3MBTL3 rs13209574, ZFAT rs13267329, CEP57 rs35793328, PCGF2 rs1985352 and MC4R rs66922415. Furthermore, several genes, many of which are involved in immune system processes, were significantly enriched with differentially methylated sites associated with LMI. Shorter telomeres were also associated with both sarcopenia and frailty. Notably, a significant relationship was observed between telomere length and methylation levels in genes related to lifestyle traits and the risk of developing these conditions. These findings provide new insights into the biological mechanisms underlying sarcopenia and frailty, underscoring the important roles of genetic and epigenetic factors in their pathogenesis among older adults.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1113/EP092853","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Sarcopenia and frailty are complex geriatric syndromes influenced by a combination of genetic and environmental factors. Recent studies suggest that specific genetic variants, DNA methylation patterns and shortened telomeres are associated with age-related diseases and might contribute to the development of both sarcopenia and frailty. In this study, we investigated the contribution of multi-omics data to sarcopenia, frailty, lean mass index (LMI) and handgrip strength in an elderly Lithuanian population. A total of 204 participants (age 82.2 ± 7.6 years) were included, comprising 122 individuals diagnosed with sarcopenia and/or frailty and 82 healthy, community-dwelling older adults. The results showed that LMI was associated with various health and lifestyle factors. Two genetic variants, CLIC5 rs75652203 and GHITM rs17102732, were found to be significantly associated with handgrip strength at the genome-wide level. Additionally, 12 polymorphisms previously linked to sarcopenia were replicated in relationship to LMI: BOK rs76993203, VAMP5 rs1374370, TMEM18 rs12714414, SFMBT1 rs36033494, BANK1 rs13136118, TET2 rs2647239, FOXO3 rs9384679, L3MBTL3 rs13209574, ZFAT rs13267329, CEP57 rs35793328, PCGF2 rs1985352 and MC4R rs66922415. Furthermore, several genes, many of which are involved in immune system processes, were significantly enriched with differentially methylated sites associated with LMI. Shorter telomeres were also associated with both sarcopenia and frailty. Notably, a significant relationship was observed between telomere length and methylation levels in genes related to lifestyle traits and the risk of developing these conditions. These findings provide new insights into the biological mechanisms underlying sarcopenia and frailty, underscoring the important roles of genetic and epigenetic factors in their pathogenesis among older adults.
期刊介绍：
Experimental Physiology publishes research papers that report novel insights into homeostatic and adaptive responses in health, as well as those that further our understanding of pathophysiological mechanisms in disease. We encourage papers that embrace the journal’s orientation of translation and integration, including studies of the adaptive responses to exercise, acute and chronic environmental stressors, growth and aging, and diseases where integrative homeostatic mechanisms play a key role in the response to and evolution of the disease process. Examples of such diseases include hypertension, heart failure, hypoxic lung disease, endocrine and neurological disorders. We are also keen to publish research that has a translational aspect or clinical application. Comparative physiology work that can be applied to aid the understanding human physiology is also encouraged.
Manuscripts that report the use of bioinformatic, genomic, molecular, proteomic and cellular techniques to provide novel insights into integrative physiological and pathophysiological mechanisms are welcomed.
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