Epigenetic predictors of maximum lifespan and other life history traits in mammals

Chengzhang Li(University of California, Los Angeles), Amin Haghani, Todd R. Robeck, Diego Villar, Aimei Lu, Joshua Zhang, Christopher G. Faulkes, Ha Vu, Julia Ablaeva, Denise M. Adams, Reza Ardehali, A Arneson, C. Scott Baker, Katherine Belov, Daniel T. Blumstein, Eleanor K. Bors, Charles E. Breeze, Robert T. Brooke, Janine L. Brown, Alex Caulton, Julie M. Cavin, Ioulia Chatzistamou, Hao Chen, Priscila Chiavellini, Oi‐Wa Choi, Shannon Clarke, Joseph DeYoung, Candice K. Emmons, Stephan Emmrich, Zhe Fei, Steven H. Ferguson, Carrie J. Finno, Jennifer E. Flower, Jean‐Michel Gaillard, Eva Garde, Vadim N. Gladyshev, Rodolfo G. Goya, M. Bradley Hanson, Martin Haulena, K. Herrick, Andrew N. Hogan, Carolyn J. Hogg, T.A. Hore, 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, Brenda Larison, Sang‐Goo Lee, Marina Lehmann, Jean‐François Lemaître, Andrew J. Levine, Chunquan Li, X. Li, David Lin, D. Lindemann, Nicholas Macoretta, Debra Maddox, Craig O. Matkin, Julie A. Mattison, June Mergl, J.J. Meudt, Gisele Montano, Khyobeni Mozhui, Asieh Naderi, Martina Nagy, Pritika Narayan, Peter W. Nathanielsz, Ngọc Bích Nguỹên, Christof Niehrs, Duncan T. Odom, Alexander G. Ophir, Elaine A. Ostrander, Perrie O’Tierney-Ginn, Kim M. Parsons, Kaninika Paul, Matteo Pellegrini, Gabriela Medeiros de Pinho, Jocelyn Plassais, Natalia A. Prado, 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, Lars Schomacher, Lawrence B. Schook, Karen E. Sears, Ashley W. Seifert, Anastasia V. Shindyapina, Kavita Singh, Indranil Sinha, Russell G. Snell, Elham Soltanmohammadi, Matthew L Spangler, Matthew Spriggs, Karen J. Steinman, Victoria J Sugrue, Balázs Szladovits, M. Takasugi, Emma C. Teeling, B. Van Bonn, Sonja C. Vernes, Harry V. Vinters, Mary C. Wallingford, Nan Wang, Gerald S. Wilkinson, Robert W. Williams, X. William Yang, B. G. Young, Bohan Zhang, Zhihui Zhang, P. Zhao, Yang Zhao, Wei Zhou, Joseph A. Zoller, Jason Ernst, Andrei Seluanov, K. Raj, Vera Gorbunova, Steve Horvath
bioRxiv (Cold Spring Harbor Laboratory)
May 18, 2021
10.1101/2021.05.16.444078
Cited by 17Open Access
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Abstract

Abstract Maximum lifespan of a species is the oldest that individuals can survive, reflecting the genetic limit of longevity in an ideal environment. Here we report methylation-based models that accurately predict maximum lifespan (r=0.89), gestational time (r=0.96), and age at sexual maturity (r=0.87), using cytosine methylation patterns collected from over 12,000 samples derived from 192 mammalian species. Our epigenetic maximum lifespan predictor corroborated the extended lifespan in growth hormone receptor knockout mice and rapamycin treated mice. Across dog breeds, epigenetic maximum lifespan correlates positively with breed lifespan but negatively with breed size. Lifespan-related cytosines are located in transcriptional regulatory regions, such as bivalent chromatin promoters and polycomb-repressed regions, which were hypomethylated in long-lived species. The epigenetic estimators of maximum lifespan and other life history traits will be useful for characterizing understudied species and for identifying interventions that extend lifespan.

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