Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning
Sillanpää, E., Heikkinen, A., Kankaanpää, A., Paavilainen, A., Kujala, U. M., Tammelin, T. H., Kovanen, V., Sipilä, S., Pietiläinen, K. H., Kaprio, J., Ollikainen, M., & Laakkonen, E. K. (2021). Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning. Clinical Epigenetics, 13, Article 110. https://doi.org/10.1186/s13148-021-01094-6
Published inClinical Epigenetics
DisciplineLiikuntalääketiedeGerontologia ja kansanterveysGerontologian tutkimuskeskusSports and Exercise MedicineGerontology and Public HealthGerontology Research Center
© The Author(s) 2021
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. ...
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- Liikuntatieteiden tiedekunta 
Related funder(s)Academy of Finland
Funding program(s)Research post as Academy Research Fellow, AoF; Academy Project, AoF; Research costs of Academy Research Fellow, AoF
Additional information about fundingES was supported by the Academy of Finland (Grant No. 260001), the Juho Vainio foundation and the Yrjö Jahnsson foundation. VK was supported by the Academy of Finland (275323). KHP was funded by the Academy of Finland (Grant Nos. 314383 and 266286), the Academy of Finland Center of Excellence in Research on Mitochondria, Metabolism and Disease (FinMIT; Grant No. 272376), the Finnish Medical Foundation, the Gyllenberg Foundation, the Novo Nordisk Foundation (Grant Nos. NNF17OC0027232 and NNF10OC1013354), the Finnish Diabetes Research Foundation, the Finnish Foundation for Cardiovascular Research, Government Research Funds, the University of Helsinki and Helsinki University Hospital. JK was supported by the Academy of Finland (213506, 308248, 312073, 336823), EC FP5 GenomEUtwin, NIH NIH/NHLBI (grant HL104125), EC MC ITN Project EPITRAIN and Sigrid Juselius Foundation. MO was supported by the Academy of Finland (297908 and 251316), EC MC ITN Project EPITRAIN, University of Helsinki Research Funds and Sigrid Juselius Foundation. EKL was supported by the Academy of Finland (309504 and 314181) and the Juho Vainio Foundation. ...
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