Castration delays epigenetic aging and feminizes DNA methylation at androgen-regulated loci.

Autor:	Sugrue VJ; Department of Anatomy, University of Otago, Dunedin, New Zealand., Zoller JA; Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, United States., Narayan P; Applied Translational Genetics Group, School of Biological Sciences, Centre for Brain Research, The University of Auckland, Auckland, New Zealand., Lu AT; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States., Ortega-Recalde OJ; Department of Anatomy, University of Otago, Dunedin, New Zealand., Grant MJ; Applied Translational Genetics Group, School of Biological Sciences, Centre for Brain Research, The University of Auckland, Auckland, New Zealand., Bawden CS; Livestock and Farming Systems, South Australian Research and Development Institute, Roseworthy, Australia., Rudiger SR; Livestock and Farming Systems, South Australian Research and Development Institute, Roseworthy, Australia., Haghani A; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States., Bond DM; Department of Anatomy, University of Otago, Dunedin, New Zealand., Hore RR; Blackstone Hill Station, Becks, RD2, Omakau, New Zealand., Garratt M; Department of Anatomy, University of Otago, Dunedin, New Zealand., Sears KE; Department of Ecology and Evolutionary Biology, UCLA, Los Angeles, United States., Wang N; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles (UCLA), Los Angeles, United States., Yang XW; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles (UCLA), Los Angeles, United States.; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, United States., Snell RG; Applied Translational Genetics Group, School of Biological Sciences, Centre for Brain Research, The University of Auckland, Auckland, New Zealand., Hore TA; Department of Anatomy, University of Otago, Dunedin, New Zealand., Horvath S; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Jul 06; Vol. 10. Date of Electronic Publication: 2021 Jul 06.
DOI:	10.7554/eLife.64932
Abstrakt:	In mammals, females generally live longer than males. Nevertheless, the mechanisms underpinning sex-dependent longevity are currently unclear. Epigenetic clocks are powerful biological biomarkers capable of precisely estimating chronological age and identifying novel factors influencing the aging rate using only DNA methylation data. In this study, we developed the first epigenetic clock for domesticated sheep ( Ovis aries ), which can predict chronological age with a median absolute error of 5.1 months. We have discovered that castrated male sheep have a decelerated aging rate compared to intact males, mediated at least in part by the removal of androgens. Furthermore, we identified several androgen-sensitive CpG dinucleotides that become progressively hypomethylated with age in intact males, but remain stable in castrated males and females. Comparable sex-specific methylation differences in MKLN1 also exist in bat skin and a range of mouse tissues that have high androgen receptor expression, indicating that it may drive androgen-dependent hypomethylation in divergent mammalian species. In characterizing these sites, we identify biologically plausible mechanisms explaining how androgens drive male-accelerated aging. Competing Interests: VS, JZ, PN, AL, OO, MG, CB, SR, AH, MG, KS, NW, XY, RS No competing interests declared, DB Director and shareholder of Totovision, a small agricultural consultancy. RH Commercial sheep famer, TH is a shareholder and director of Totovision Ltd, a small agricultural and biotechnology consultancy. SH is a founder of the non-profit Epigenetic Clock Development Foundation which plans to license several patents from his employer UC Regents, including a patent for the mammalian assay utilised in this study (WO2020150705). (© 2021, Sugrue et al.)
Databáze:	MEDLINE
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