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Journal of Cachexia, Sarcopenia and Muscle
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An epigenetic clock for human skeletal muscle

Authors: Voisin, S; Harvey, NR; Haupt, LM; Griffiths, LR; Ashton, KJ; Coffey, VG; Doering, TM; +9 Authors

An epigenetic clock for human skeletal muscle

Abstract

Abstract 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 arrays (HM27, HM450 or HMEPIC). We also took advantage of the large number of samples to conduct an epigenome-wide association study (EWAS) of age-associated DNA methylation patterns in skeletal muscle. Results The newly developed clock uses 200 CpGs to estimate chronological age in skeletal muscle, 16 of which are in common with the 353 CpGs 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 (DMRs) 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 pan-tissue clock. We implemented the muscle clock in an R package called MEAT 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.

Countries
Australia, Sweden, United Kingdom
Keywords

Adult, Epigenomics, Male, 570, Epigenetic clock, Adolescent, Epigenetic age, Institute for Health and Sport, QH301 Biology, Biological age, DMPs, 610, Skeletal muscle, QH426 Genetics, Diseases of the musculoskeletal system, Medical Genetics and Genomics, QH301, Young Adult, RC925, chromatin states, Humans, Fysiologi och anatomi, Muscle, Skeletal, QH426, 060404 Epigenetics (incl. Genome Methylation and Epigenomics), Aged, QM, Aged, 80 and over, 0604 Genetics, DNA methylation, QM1-695, Original Articles, Differentially Methylated Positions, Physiology and Anatomy, Middle Aged, human skeletal muscle, DNA methylation datasets, QM Human anatomy, R1, Medicinsk genetik och genomik, Ageing, RC925-935, 1116 Medical Physiology, Human anatomy, Female

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    selected citations
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    99
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
99
Top 1%
Top 10%
Top 1%
Green
Published in a Diamond OA journal