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An epigenetic clock for human skeletal muscle

journal contribution
posted on 31.08.2020, 00:00 by S Voisin, NR Harvey, LM Haupt, LR Griffiths, KJ Ashton, VG Coffey, Thomas DoeringThomas Doering, JM Thompson, C Benedict, J Cedernaes
Background Ageing is associated with DNA methylation changes in all human tissues, and epigenetic markers can estimate chronological age based on DNA methylation patterns across tissues. However, the construction of the original pan-tissue epigenetic clock did not include skeletal muscle samples and hence exhibited a strong deviation between DNA methylation and chronological age in this tissue. Methods To address this, we developed a more accurate, muscle-specific epigenetic clock based on the genome-wide DNA methylation data of 682 skeletal muscle samples from 12 independent datasets (18–89 years old, 22% women, 99% Caucasian), all generated with Illumina HumanMethylation (HM) arrays (HM27, HM450, or HMEPIC). We also took advantage of the large number of samples to conduct an epigenome-wide association study of age-associated DNA methylation patterns in skeletal muscle. Results The newly developed clock uses 200 cytosine-phosphate–guanine dinucleotides to estimate chronological age in skeletal muscle, 16 of which are in common with the 353 cytosine-phosphate–guanine dinucleotides of the pan-tissue clock.The muscle clock outperformed the pan-tissue clock, with a median error of only 4.6 years across datasets (vs. 13.1 years for the pan-tissue clock, P < 0.0001) and an average correlation of ρ = 0.62 between actual and predicted age across datasets (vs.ρ = 0.51 for the pan-tissue clock). Lastly, we identified 180 differentially methylated regions with age in skeletal muscle at a false discovery rate < 0.005. However, gene set enrichment analysis did not reveal any enrichment for gene ontologies. Conclusions We have developed a muscle-specific epigenetic clock that predicts age with better accuracy than the pantissue clock. We implemented the muscle clock in an R package called Muscle Epigenetic Age Test available on BIOCONDUCTOR to estimate epigenetic age in skeletal muscle samples. This clock may prove valuable in assessing the impact of environmental factors, such as exercise and diet, on muscle-specific biological ageing processes.

Funding

Other

History

Volume

11

Issue

4

Start Page

887

End Page

898

Number of Pages

12

eISSN

2190-6009

ISSN

2190-5991

Publisher

Wiley

Additional Rights

CC BY 4.0

Language

en

Peer Reviewed

Yes

Open Access

Yes

Acceptance Date

30/01/2020

External Author Affiliations

Norwegian School of Sport Sciences; Massey University, NZ; Deakin University; University of California Los Angeles, Stanford University, US; Victoria University; Bond University; Queensland University of Technology; Uppsala University, Sweden

Era Eligible

Yes

Journal

Journal of Cachexia, Sarcopenia and Muscle