A multi‐omics investigation of sarcopenia and frailty: Integrating genomic, epigenomic and telomere length data

Ginevičienė, V; Pranckevičienė, E; Urnikytė, A; Jurkūnaitė, L; Gutauskaitė, K; Dadelienė, R; Kilaitė, J; Jamontaitė, IE; Mastavičiūtė, A; Ahmetov, II; Alekna, V

A multi‐omics investigation of sarcopenia and frailty: Integrating genomic, epigenomic and telomere length data

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Ginevičienė, V ORCID: 0000-0003-4956-6307, Pranckevičienė, E, Urnikytė, A, Jurkūnaitė, L, Gutauskaitė, K, Dadelienė, R, Kilaitė, J, Jamontaitė, IE, Mastavičiūtė, A, Ahmetov, II ORCID: 0000-0002-6335-4020 and Alekna, V (2025) A multi‐omics investigation of sarcopenia and frailty: Integrating genomic, epigenomic and telomere length data. Experimental Physiology. ISSN 0958-0670

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Publisher URL: https://doi.org/10.1113/ep092853

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.

Item Type:	Article
Uncontrolled Keywords:	0606 Physiology; 1106 Human Movement and Sports Sciences; 1116 Medical Physiology; Physiology; 3109 Zoology; 3208 Medical physiology; 4207 Sports science and exercise
Subjects:	Q Science > QP Physiology
Divisions:	Sport and Exercise Sciences
Publisher:	Wiley
Date of acceptance:	28 August 2025
Date of first compliant Open Access:	29 September 2025
Date Deposited:	29 Sep 2025 10:43
Last Modified:	29 Sep 2025 11:00
DOI or ID number:	10.1113/ep092853
URI:	https://researchonline.ljmu.ac.uk/id/eprint/27215

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