Cargando…

An epigenetic clock for human skeletal muscle

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 an...

Descripción completa

Detalles Bibliográficos
Autores principales: Voisin, Sarah, Harvey, Nicholas R., Haupt, Larisa M., Griffiths, Lyn R., Ashton, Kevin J., Coffey, Vernon G., Doering, Thomas M., Thompson, Jamie‐Lee M., Benedict, Christian, Cedernaes, Jonathan, Lindholm, Malene E., Craig, Jeffrey M., Rowlands, David S., Sharples, Adam P., Horvath, Steve, Eynon, Nir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432573/
https://www.ncbi.nlm.nih.gov/pubmed/32067420
http://dx.doi.org/10.1002/jcsm.12556
_version_ 1783571829500149760
author Voisin, Sarah
Harvey, Nicholas R.
Haupt, Larisa M.
Griffiths, Lyn R.
Ashton, Kevin J.
Coffey, Vernon G.
Doering, Thomas M.
Thompson, Jamie‐Lee M.
Benedict, Christian
Cedernaes, Jonathan
Lindholm, Malene E.
Craig, Jeffrey M.
Rowlands, David S.
Sharples, Adam P.
Horvath, Steve
Eynon, Nir
author_facet Voisin, Sarah
Harvey, Nicholas R.
Haupt, Larisa M.
Griffiths, Lyn R.
Ashton, Kevin J.
Coffey, Vernon G.
Doering, Thomas M.
Thompson, Jamie‐Lee M.
Benedict, Christian
Cedernaes, Jonathan
Lindholm, Malene E.
Craig, Jeffrey M.
Rowlands, David S.
Sharples, Adam P.
Horvath, Steve
Eynon, Nir
author_sort Voisin, Sarah
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7432573
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-74325732020-08-20 An epigenetic clock for human skeletal muscle Voisin, Sarah Harvey, Nicholas R. Haupt, Larisa M. Griffiths, Lyn R. Ashton, Kevin J. Coffey, Vernon G. Doering, Thomas M. Thompson, Jamie‐Lee M. Benedict, Christian Cedernaes, Jonathan Lindholm, Malene E. Craig, Jeffrey M. Rowlands, David S. Sharples, Adam P. Horvath, Steve Eynon, Nir J Cachexia Sarcopenia Muscle Original Articles 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. John Wiley and Sons Inc. 2020-02-17 2020-08 /pmc/articles/PMC7432573/ /pubmed/32067420 http://dx.doi.org/10.1002/jcsm.12556 Text en © 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Voisin, Sarah
Harvey, Nicholas R.
Haupt, Larisa M.
Griffiths, Lyn R.
Ashton, Kevin J.
Coffey, Vernon G.
Doering, Thomas M.
Thompson, Jamie‐Lee M.
Benedict, Christian
Cedernaes, Jonathan
Lindholm, Malene E.
Craig, Jeffrey M.
Rowlands, David S.
Sharples, Adam P.
Horvath, Steve
Eynon, Nir
An epigenetic clock for human skeletal muscle
title An epigenetic clock for human skeletal muscle
title_full An epigenetic clock for human skeletal muscle
title_fullStr An epigenetic clock for human skeletal muscle
title_full_unstemmed An epigenetic clock for human skeletal muscle
title_short An epigenetic clock for human skeletal muscle
title_sort epigenetic clock for human skeletal muscle
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432573/
https://www.ncbi.nlm.nih.gov/pubmed/32067420
http://dx.doi.org/10.1002/jcsm.12556
work_keys_str_mv AT voisinsarah anepigeneticclockforhumanskeletalmuscle
AT harveynicholasr anepigeneticclockforhumanskeletalmuscle
AT hauptlarisam anepigeneticclockforhumanskeletalmuscle
AT griffithslynr anepigeneticclockforhumanskeletalmuscle
AT ashtonkevinj anepigeneticclockforhumanskeletalmuscle
AT coffeyvernong anepigeneticclockforhumanskeletalmuscle
AT doeringthomasm anepigeneticclockforhumanskeletalmuscle
AT thompsonjamieleem anepigeneticclockforhumanskeletalmuscle
AT benedictchristian anepigeneticclockforhumanskeletalmuscle
AT cedernaesjonathan anepigeneticclockforhumanskeletalmuscle
AT lindholmmalenee anepigeneticclockforhumanskeletalmuscle
AT craigjeffreym anepigeneticclockforhumanskeletalmuscle
AT rowlandsdavids anepigeneticclockforhumanskeletalmuscle
AT sharplesadamp anepigeneticclockforhumanskeletalmuscle
AT horvathsteve anepigeneticclockforhumanskeletalmuscle
AT eynonnir anepigeneticclockforhumanskeletalmuscle
AT voisinsarah epigeneticclockforhumanskeletalmuscle
AT harveynicholasr epigeneticclockforhumanskeletalmuscle
AT hauptlarisam epigeneticclockforhumanskeletalmuscle
AT griffithslynr epigeneticclockforhumanskeletalmuscle
AT ashtonkevinj epigeneticclockforhumanskeletalmuscle
AT coffeyvernong epigeneticclockforhumanskeletalmuscle
AT doeringthomasm epigeneticclockforhumanskeletalmuscle
AT thompsonjamieleem epigeneticclockforhumanskeletalmuscle
AT benedictchristian epigeneticclockforhumanskeletalmuscle
AT cedernaesjonathan epigeneticclockforhumanskeletalmuscle
AT lindholmmalenee epigeneticclockforhumanskeletalmuscle
AT craigjeffreym epigeneticclockforhumanskeletalmuscle
AT rowlandsdavids epigeneticclockforhumanskeletalmuscle
AT sharplesadamp epigeneticclockforhumanskeletalmuscle
AT horvathsteve epigeneticclockforhumanskeletalmuscle
AT eynonnir epigeneticclockforhumanskeletalmuscle