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Sökning: WFRF:(Lee Jeffrey E.) > (2020) > An epigenetic clock...

An epigenetic clock for human skeletal muscle

Voisin, Sarah (författare)
Victoria Univ, Inst Hlth & Sport, Melbourne, Vic 8001, Australia.
Harvey, Nicholas R. (författare)
Bond Univ, Fac Hlth Sci & Med, Gold Coast, Australia.;Queensland Univ Technol, Sch Biomed Sci, Inst Hlth & Biomed Innovat, Genom Res Ctr, Brisbane, Qld, Australia.
Haupt, Larisa M. (författare)
Queensland Univ Technol, Sch Biomed Sci, Inst Hlth & Biomed Innovat, Genom Res Ctr, Brisbane, Qld, Australia.
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Griffiths, Lyn R. (författare)
Queensland Univ Technol, Sch Biomed Sci, Inst Hlth & Biomed Innovat, Genom Res Ctr, Brisbane, Qld, Australia.
Ashton, Kevin J. (författare)
Bond Univ, Fac Hlth Sci & Med, Gold Coast, Australia.
Coffey, Vernon G. (författare)
Bond Univ, Fac Hlth Sci & Med, Gold Coast, Australia.
Doering, Thomas M. (författare)
Bond Univ, Fac Hlth Sci & Med, Gold Coast, Australia.;Cent Queensland Univ, Sch Hlth Med & Appl Sci, Rockhampton, Qld, Australia.
Thompson, Jamie-Lee M. (författare)
Bond Univ, Fac Hlth Sci & Med, Gold Coast, Australia.
Benedict, Christian, Docent, 1976- (författare)
Uppsala Univ, Dept Neurosci, Sleep Res Lab, Uppsala, Sweden.
Cedernaes, Jonathan (författare)
Uppsala universitet,Transplantation och regenerativ medicin
Lindholm, Malene E. (författare)
Karolinska Institutet
Craig, Jeffrey M. (författare)
Deakin Univ, Ctr Mol & Med Res, Geelong, Vic, Australia.;Royal Childrens Hosp, Murdoch Childrens Res Inst, Epigenet, Melbourne, Vic, Australia.
Rowlands, David S. (författare)
Massey Univ, Sch Sport Exercise & Nutr, Wellington, New Zealand.
Sharples, Adam P. (författare)
Norwegian Sch Sport Sci, Dept Phys Performance, Oslo, Norway.;Liverpool John Moores Univ, Res Inst Sport & Exercise Sci, Exercise Metab & Adaptat Res Grp, Stem Cells Ageing & Mol Physiol Unit, Liverpool, Merseyside, England.
Horvath, Steve (författare)
Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet & Biostat, Los Angeles, CA 90095 USA.
Eynon, Nir (författare)
Victoria Univ, Inst Hlth & Sport, Melbourne, Vic 8001, Australia.
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Victoria Univ, Inst Hlth & Sport, Melbourne, Vic 8001, Australia Bond Univ, Fac Hlth Sci & Med, Gold Coast, Australia.;Queensland Univ Technol, Sch Biomed Sci, Inst Hlth & Biomed Innovat, Genom Res Ctr, Brisbane, Qld, Australia. (creator_code:org_t)
2020-02-17
2020
Engelska.
Ingår i: Journal of Cachexia, Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 11:4, s. 887-898
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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 pan‐tissue 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. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

Skeletal muscle
Epigenetic clock
Ageing
DNA methylation
Epigenetic age
Biological age

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