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Record W4385726786 · doi:10.1038/s43587-023-00462-6

Universal DNA methylation age across mammalian tissues

2023· article· en· W4385726786 on OpenAlexaff
Ake T. Lu, Zhe Fei, Amin Haghani, Todd R. Robeck, Joseph A. Zoller, Caesar Z. Li, Robert Lowe, Qi Yan, Joshua Zhang, Hoang‐Giang Vu, Julia Ablaeva, Victoria A. Acosta-Rodríguez, Danielle M. Adams, Javier Almunia, Ajoy Aloysius, Reza Ardehali, A Arneson, C. Scott Baker, Gareth Banks, Katherine Belov, Nigel C. Bennett, Peter C. Black, Daniel T. Blumstein, Eleanor K. Bors, Charles E. Breeze, Robert T. Brooke, Janine L. Brown, Gerald G. Carter, Alex Caulton, Julie M. Cavin, Lisa Chakrabarti, Ioulia Chatzistamou, Hao Chen, Kai Cheng, Priscila Chiavellini, Oi‐Wa Choi, Shannon Clarke, Lisa Noelle Cooper, Marie‐Laurence Cossette, Joanna Day, Joseph DeYoung, Stacy DiRocco, Christopher Dold, Erin E. Ehmke, Candice K. Emmons, Stephan Emmrich, Ebru Erbay, Claire Erlacher‐Reid, Chris G. Faulkes, Steven H. Ferguson, Carrie J. Finno, Jennifer E. Flower, Jean‐Michel Gaillard, Eva Garde, Livia Gerber, Vadim N. Gladyshev, Vera Gorbunova, Rodolfo G. Goya, Myles J.A. Grant, C. B. Green, Erin N. Hales, M. Bradley Hanson, Daniel W. Hart, Martin Haulena, K. Herrick, Andrew N. Hogan, Carolyn J. Hogg, Timothy A. Hore, Taosheng Huang, Juan Carlos Izpisúa Belmonte, Anna J. Jasinska, Gareth Jones, Eve Jourdain, Olga Kashpur, Harold L. Katcher, Etsuko Katsumata, Vimala Kaza, Hippokratis Kiaris, Michael S. Kobor, Paweł Kordowitzki, William R. Koski, Michael Krützen, Soon‐Bae Kwon, Brenda Larison, Sang‐Goo Lee, Marina Lehmann, Jean‐François Lemaître, Arnold J. Levine, Chunquan Li, X. Li, A. R. Lim, David Lin, D. Lindemann, Tom J. Little, Nicholas Macoretta, Debra Maddox, Craig O. Matkin, Julie A. Mattison, Mélanie McClure, June Mergl, Jennifer J. Meudt, Gisele Montano, Khyobeni Mozhui, Jason Munshi‐South, Asieh Naderi, Martina Nagy, Pritika Narayan, Peter W. Nathanielsz, Ngọc Bích Nguỹên, Christof Niehrs, Justine K. O’Brien, Perrie O’Tierney-Ginn, Duncan T. Odom, Alexander G. Ophir, S. B. Osborn, Elaine A. Ostrander, Kim M. Parsons, Kaninika Paul, Matteo Pellegrini, Katharina J. Peters, Amy B. Pedersen, Jessica L. Petersen, Darren W. Pietersen, Gabriela Medeiros de Pinho, Jocelyn Plassais, Jesse R. Poganik, Natalia A. Prado, Pradeep Reddy, Benjamin Rey, Beate Ritz, Jooke Robbins, Magdalena Rodríguez, Jennifer Russell, Elena Rydkina, Lindsay L. Sailer, Adam B. Salmon, Akshay Sanghavi, Kyle M. Schachtschneider, Dennis Schmitt, Todd L. Schmitt, Lars Schomacher, Lawrence B. Schook, Karen E. Sears, A. W. Seifert, Andrei Seluanov, Aaron B. A. Shafer, Dhanansayan Shanmuganayagam, Anastasia V. Shindyapina, M. Simmons, Kavita Singh, Indranil Sinha, Jesse Slone, Russell G. Snell, E. Soltanmaohammadi, Matthew L Spangler, M. C. Spriggs, Lydia Staggs, Nicole Stedman, Karen J. Steinman, Donald T. Stewart, Victoria J Sugrue, Balázs Szladovits, Joseph S. Takahashi, M. Takasugi, Emma C. Teeling, Michael J. Thompson, B. Van Bonn, Sonja C. Vernes, Diego Villar, Harry V. Vinters, Mary C. Wallingford, Nan Wang, Robert K. Wayne, Gerald S. Wilkinson, Christopher K. Williams, Robert W. Williams, X. William Yang, M. Yao, Brent G. Young, Bohan Zhang, Zhihui Zhang, Yang Zhao, Wanding Zhou, Jörg Zimmermann, Jason Ernst, Ken Raj, Steve Horvath

Bibliographic record

VenueNature Aging · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsBC Children's HospitalLGL (Canada)University of British ColumbiaAcadia UniversityVancouver AquariumUniversity of ManitobaFisheries and Oceans CanadaTrent University
FundersNHLBI Division of Intramural ResearchNational Heart, Lung, and Blood InstituteNational Institute on AgingCenter for Information TechnologyPaul G. Allen Family FoundationNatural Environment Research CouncilDepartment of Science and Technology, Ministry of Science and Technology, IndiaJonsson Comprehensive Cancer CenterOpen Philanthropy ProjectNational Geographic SocietySight Research UKPaul G. Allen Frontiers GroupU.S. Department of Health and Human ServicesNational Institutes of HealthCancer Research UK
KeywordsDNA methylationBiologyEpigeneticsMethylationGenomic imprintingGeneticsGeneDevelopmental biologySenescenceEvolutionary biologyGene expression

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.312
Teacher spread0.301 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations387
Published2023
Admission routes1
Has abstractyes

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