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Sarcopenia is associated with hypomethylation of TWEAK and increased plasma levels of TWEAK and its downstream inflammatory factor TNF-α in older adults: A case-control study
Experimental Gerontology ( IF 3.9 ) Pub Date : 2024-03-06 , DOI: 10.1016/j.exger.2024.112390 Saiyare Xuekelati , Zhuoya Maimaitiwusiman , Xue Bai , Hong Xiang , Yangjing Li , Hongmei Wang
Experimental Gerontology ( IF 3.9 ) Pub Date : 2024-03-06 , DOI: 10.1016/j.exger.2024.112390 Saiyare Xuekelati , Zhuoya Maimaitiwusiman , Xue Bai , Hong Xiang , Yangjing Li , Hongmei Wang
Sarcopenia is a harmful condition common among older adults for which no treatment is available. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (FN14) are known to play important roles in the pathogenesis of sarcopenia. This study investigated alterations in methylation in and to identify potential targets for the managing sarcopenia. Through an epidemiological investigation, we detected methylation of CpG islands (CpGs) in TWEAK and Fn14 in community-dwelling older adult of Xinjiang by bisulfite sequencing. Significant CpGs associated with sarcopenia were selected for detection in 152 older individuals by pyrosequencing. Associations between CpG methylation, plasma inflammatory marker levels, and sarcopenia were analyzed. Of 38 CpGs in and 30 CpGs in detected in 60 individuals, 6 CpGs showed lower methylation in sarcopenia patients compared with control individuals. In 152 older adults, covariance analysis with adjustment for age, gender, triglyceride level, obesity, diabetes, and hypertension showed that the methylation levels of 6 CpGs (CpG8, CpG12, CpG13, CpG20 and CpG21of , and CpG24 of ) were significantly lower in sarcopenia patients than in control individuals. With adjustment for additional confounding factors, covariate variance analysis showed that plasma TWEAK, TNF-α and IL-10 levels in the sarcopenia group were significant higher than those in the control group ( = 0.007, < 0.001, = 0.003). Multivariate logistic regression analysis showed that CpG8, CpG13, CpG21, and total methylation of (OR = 0.767, 95 % CI = 0.622–0.947; OR = 0.740, 95 % CI = 0.583–0.941; OR = 0.734, 95 % CI = 0.561–0.958; OR = 0.883, 95 % CI = 0.795–0.980) as well as CpG22 and total methylation of were significantly associated with sarcopenia (OR = 826, 95 % CI = 0.704–0.968; OR = 0.918, 95 % CI = 0.852–0.989). From partial correlation analysis, plasma TWEAK was correlated with plasma TNF-α ( = 0.172, = 0.042). Sarcopenia is associated with hypomethylation of and increased plasma levels of TWEAK and its downstream inflammatory factor TNF-α in a community-dwelling population of older adults in Xinjiang.
更新日期：2024-03-06
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