Cited by 43Epigenetics and DNA MethylationGenetics, Aging, and Longevity in Model OrganismsTelomeres, Telomerase, and Senescence

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

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Sillanpää, Elina, Heikkinen, Aino, Kankaanpää, Anna, Paavilainen, Aini, Kujala, Urho M., Tammelin, Tuija H., Kovanen, Vuokko, Sipilä, Sarianna +4 more·2021·Clinical Epigenetics

Published version of a preprint

Abstract

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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  • Epigenetic clocks trained in specific tissues have stronger associations with the functional states of those tissues.

    “This idea is further supported by studies that show that epigenetic clocks trained in specific tissues have stronger associations with the functional states of those tissues77–80.”

    From Measuring biological age using omics data (2022) · cites this paper as [80]

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Authors
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.
Affiliations
  • University of Helsinki (FI)
  • University of Jyväskylä (FI)
  • LIKES – Foundation for Sport and Health Sciences (FI)
Corresponding author
Sillanpää, Elina
Venue
Clinical Epigenetics
Published
2021-05-17
Volume
13
Issue
1
Pages
110-110
ISSN
  • 1868-7075 (ISSN-L)
  • 1868-7083
OpenAlex
W3163231593
Cited by
43
References
64
Citations by year
2026: 11 · 2025: 7 · 2024: 10 · 2023: 8 · 2022: 6 · 2021: 1
FWCI
1.96
Type
journal article
Language
en
Open access
Locations
  • Clinical Epigenetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Jyväskylä University Digital Archive (University of Jyväskylä) (submittedVersion, cc-by)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
  • Academy of Finland (260001, 275323, 314383, 266286, 213506, 308248, 312073, 336823, 297908, 251316, 309504, 314181)
  • Juho Vainion Säätiö
  • Yrjö Jahnssonin Säätiö
  • Acedemy of Finland Center of Excellence in Research on Mitochondria, Metabolism and Disease (272376)
  • Suomen Lääketieteen Säätiö
  • Signe ja Ane Gyllenbergin Säätiö
  • Novo Nordisk Fonden (NNF17OC0027232, NNF10OC1013354)
  • Finnish Diabetes foundation
  • Finnish foundation for cardiovascular health
  • Finnish government research funds
  • Helsinki University Hospital
  • EC FP5 GenomEUTwin
  • National Institutes of Health (HL104125)
  • EC MC ITN (EPITRAIN)
  • Sigrid Juséliuksen Säätiö
  • University of Helsinki research funds
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Keywords
epigenetic clocks, DNA methylation age, skeletal muscle aging, physical activity, physical function, body composition, cardiorespiratory fitness, muscle strength, monozygotic twin concordance, Horvath clock, GrimAge, meat, accelerated aging, smoking, sex differences
MeSH terms
Adult, Aged, Aging, Female, Humans, Male, Middle Aged, Cohort Studies, Exercise, Muscle, Skeletal, DNA Methylation, Epigenesis, Genetic, Young Adult, Epigenomics

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