Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning

Clinical Epigenetics

Urho M. Kujala¹  Vuokko Kovanen²  Eija K. Laakkonen²  Sarianna Sipilä²  Anna Kankaanpää²  Aini Paavilainen²  Elina Sillanpää³  Jaakko Kaprio⁴  Miina Ollikainen⁵  Aino Heikkinen⁵  Tuija H. Tammelin⁶  Kirsi H. Pietiläinen⁷ 

[1] Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland;Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, P.O. Box 35 (VIV), 40014, Jyväskylä, Finland;Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, P.O. Box 35 (VIV), 40014, Jyväskylä, Finland;Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland;Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland;Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland;Department of Public Health, University of Helsinki, Helsinki, Finland;LIKES Research Centre for Physical Activity and Health, Jyväskylä, Finland;Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland;Obesity Center, Endocrinology, Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland;

关键词: DNA methylation;    Biological ageing;    Twin study;    Maximal oxygen consumption;    Muscle strength;    Dual-energy X-ray absorptiometry;    Muscle mass;   

DOI  :  10.1186/s13148-021-01094-6

来源: Springer

【 摘 要 】

The aim of this study was to investigate the correspondence of different biological ageing estimates (i.e. epigenetic age) in blood and muscle tissue and their associations with physical activity (PA), physical function and body composition. Two independent cohorts (N = 139 and N = 47) were included, whose age span covered adulthood (23–69 years). Whole blood and m. vastus lateralis samples were collected, and DNA methylation was analysed. Four different DNA methylation age (DNAmAge) estimates were calculated using genome-wide methylation data and publicly available online tools. A novel muscle-specific methylation age was estimated using the R-package ‘MEAT’. PA was measured with questionnaires and accelerometers. Several tests were conducted to estimate cardiorespiratory fitness and muscle strength. Body composition was estimated by dual-energy X-ray absorptiometry. DNAmAge estimates from blood and muscle were highly correlated with chronological age, but different age acceleration estimates were weakly associated with each other. The monozygotic twin within-pair similarity of ageing pace was higher in blood (r = 0.617–0.824) than in muscle (r = 0.523–0.585). Associations of age acceleration estimates with PA, physical function and body composition were weak in both tissues and mostly explained by smoking and sex. The muscle-specific epigenetic clock MEAT was developed to predict chronological age, which may explain why it did not associate with functional phenotypes. The Horvath’s clock and GrimAge were weakly associated with PA and related phenotypes, suggesting that higher PA would be linked to accelerated biological ageing in muscle. This may, however, be more reflective of the low capacity of epigenetic clock algorithms to measure functional muscle ageing than of actual age acceleration. Based on our results, the investigated epigenetic clocks have rather low value in estimating muscle ageing with respect to the physiological adaptations that typically occur due to ageing or PA. Thus, further development of methods is needed to gain insight into muscle tissue-specific ageing and the underlying biological pathways.

【 授权许可】

CC BY