Universal DNA methylation age across mammalian tissues

被引：159

作者：

Lu, A. T. ^{[1
,2
]}

Fei, Z. ^{[3
,4
]}

Haghani, A. ^{[1
,2
]}

Robeck, T. R. ^{[5
]}

Zoller, J. A. ^{[3
]}

Li, C. Z. ^{[3
]}

Lowe, R. ^{[6
]}

Yan, Q. ^{[2
]}

Zhang, J. ^{[1
]}

Vu, H. ^{[79
]}

Ablaeva, J. ^{[9
]}

Acosta-Rodriguez, V. A. ^{[10
]}

Adams, D. M. ^{[11
]}

Almunia, J. ^{[12
]}

Aloysius, A. ^{[13
]}

Ardehali, R. ^{[14
]}

Arneson, A. ^{[7
,8
]}

Baker, C. S. ^{[15
]}

Banks, G. ^{[16
]}

Belov, K. ^{[17
]}

Bennett, N. C. ^{[18
]}

Black, P. ^{[19
]}

Blumstein, D. T. ^{[20
,21
]}

Bors, E. K. ^{[15
]}

Breeze, C. E. ^{[22
]}

Brooke, R. T. ^{[23
]}

Brown, J. L. ^{[24
]}

Carter, G. G. ^{[25
]}

Caulton, A. ^{[26
,27
]}

Cavin, J. M. ^{[28
]}

Chakrabarti, L. ^{[29
]}

Chatzistamou, I. ^{[30
]}

Chen, H. ^{[31
]}

Cheng, K. ^{[32
]}

Chiavellini, P. ^{[33
]}

Choi, O. W. ^{[34
]}

Clarke, S. M. ^{[26
]}

Cooper, L. N. ^{[35
]}

Cossette, M. L. ^{[36
]}

Day, J. ^{[37
]}

DeYoung, J. ^{[34
]}

DiRocco, S. ^{[38
]}

Dold, C. ^{[39
]}

Ehmke, E. E. ^{[40
]}

Emmons, C. K. ^{[41
]}

Emmrich, S. ^{[42
,43
]}

Erbay, E. ^{[44
]}

Erlacher-Reid, C. ^{[45
]}

Faulkes, C. G. ^{[46
]}

Ferguson, S. H. ^{[47
,48
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA

[2] San Diego Inst Sci, Altos Labs, San Diego, CA 90095 USA

[3] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA

[4] Univ Calif Riverside, Dept Stat, Riverside, CA USA

[5] Zool SeaWorld Parks & Entertainment, Orlando, FL USA

[6] Cambridge Inst Sci, Altos Labs, Cambridge, England

[7] Univ Calif Los Angeles, Bioinformat Interdept Program, Los Angeles, CA USA

[8] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA USA

[9] Univ Rochester, Dept Biol, Rochester, NY 14627 USA

[10] Univ Texas Southwestern Med Ctr Dallas, Peter ODonnell Jr Brain Inst, Dept Neurosci, Dallas, TX USA

[11] Univ Maryland, Dep Biol, College Pk, MD USA

[12] Loro Parque Fdn, Puerto La Cruz, Spain

[13] Univ Kentucky, Dept Biol, Lexington, KY USA

[14] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Dept Internal Med, Los Angeles, CA USA

[15] Oregon State Univ, Marine Mammal Inst, Newport, OR USA

[16] Nottingham Trent Univ, Sch Sci & Technol, Clifton Campus, Nottingham, England

[17] Univ Sydney, Sch Life & Environm Sci, Sydney, NSW, Australia

[18] Univ Pretoria, Dept Zool & Entomol, Hatfield, Herts, South Africa

[19] Busch Gardens Tampa, Tampa, FL USA

[20] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA

[21] Rocky Mt Biol Labs, Crested Butte, CO USA

[22] Altius Inst Biomed Sci, Seattle, WA USA

[23] Epigenet Clock Dev Fdn, Los Angeles, CA USA

[24] Smithsonian Conservat Biol Inst, Ctr Species Survival, Front Royal, VA USA

[25] Ohio State Univ, Dept Evolut Ecol & Organismal Biol, Columbus, OH USA

[26] AgResearch, Invermay Agr Ctr, Mosgiel, New Zealand

[27] Univ Otago, Dept Biochem, Dunedin, New Zealand

[28] Dolphin Co, Gulf World, Panama City, FL USA

[29] Univ Nottingham, Sch Vet Med & Sci, Nottingham, England

[30] Univ South Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC USA

[31] Univ Tennessee Hlth Sci Ctr, Dept Pharmacol Addict Sci & Toxicol, Memphis, TN USA

[32] Univ Calif Los Angeles, David Geffen Sch Med, Med Informat, Los Angeles, CA USA

[33] Univ La Plata, Biochem Res Inst La Plata Histol & Pathol, Sch Med, La Plata, Argentina

[34] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, David Geffen Sch Med, Dept Psychiat & Biobehav Sci,Ctr Neurobehav Genet, Los Angeles, CA USA

[35] Northeast Ohio Med Univ, Dept Anat & Neurobiol, Rootstown, OH USA

[36] Trent Univ, Dept Environm & Life Sci, Peterborough, ON, Canada

[37] Taronga Conservat Soc Australia, Taronga Inst Sci & Learning, Mosman, NSW, Australia

[38] SeaWorld Florida, Orlando, FL USA

[39] SeaWorld Parks & Entertainment, Zool Operat, Orlando, FL USA

[40] Duke Lemur Ctr, Durham, NC USA

[41] NOAA, Conservat Biol Div, Northwest Fisheries Sci Ctr, Natl Marine Fisheries Serv, Seattle, WA USA

[42] Univ Rochester, Dept Biol, Rochester, NY USA

[43] Univ Rochester, Dept Med, Rochester, NY USA

[44] Altos Labs, San Francisco, CA USA

[45] SeaWorld Orlando, Orlando, FL USA

[46] Queen Mary Univ London, Sch Biol & Behav Sci, London, England

[47] Fisheries & Oceans Canada, Inst Freshwater, Winnipeg, MB, Canada

[48] Univ Manitoba, Dept Biol Sci, Winnipeg, MB, Canada

[49] Univ Calif Los Angeles, Davis Sch Vet Med, Dept Populat Hlth & Reprod, Davis, CA USA

[50] Myst Aquarium, Mystic, CT USA

来源：

NATURE AGING | 2023年 / 3卷 / 09期

基金：

欧洲研究理事会; 美国国家卫生研究院;

关键词：

LIFE-SPAN; LONGEVITY; MICE; INFORMATION; METABOLISM; MECHANISMS; FEATURES; CELLS;

D O I：

10.1038/s43587-023-00462-6

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals. This study identifies and characterizes evolutionarily conserved cytosine methylation patterns related to age across mammals and establishes pan-mammalian epigenetic clocks.

引用

页码：1144 / +

页数：53

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