DNA methylation predicts age and provides insight into exceptional longevity of bats

Gerald S. Wilkinson(University of Maryland, College Park), Danielle M. Adams(University of Maryland, College Park), Amin Haghani(University of California, Los Angeles), Ake T. Lu(University of California, Los Angeles), Joseph A. Zoller(University of California, Los Angeles), Charles E. Breeze(Altius Institute for Biomedical Sciences), Bryan D. Arnold(Illinois College), Hope C. Ball(Northeast Ohio Medical University), Gerald G. Carter(The Ohio State University), Lisa Noelle Cooper(Northeast Ohio Medical University), Dina K. N. Dechmann(Smithsonian Tropical Research Institute), Paolo Devanna(Max Planck Institute for Psycholinguistics), Nicolas J. Fasel(University of Lausanne), Alexander V. Galazyuk(Northeast Ohio Medical University), Linus Günther(Museum für Naturkunde), Edward Hurme(University of Konstanz), Gareth Jones(University of Bristol), Mirjam Knörnschild(Smithsonian Tropical Research Institute), Ella Zoe Lattenkamp(Max Planck Institute for Psycholinguistics), Caesar Z. Li(University of California, Los Angeles), Frieder Mayer(Museum für Naturkunde), Josephine A. Reinhardt(SUNY Geneseo), Rodrigo A. Medellín(Instituto de Ecología), Martina Nagy(Museum für Naturkunde), Brian Pope, Megan L. Power(University College Dublin), Roger D. Ransome(University of Bristol), Emma C. Teeling(University College Dublin), Sonja C. Vernes(Radboud University Nijmegen), Daniel Zamora-Mejías(Instituto de Ecología), Joshua Zhang(University of California, Los Angeles), Paul A. Faure(McMaster University), Lucas J. Greville(McMaster University), L. Gerardo Herrera M.(Universidad Nacional Autónoma de México), José Juan Flores‐Martínez(Universidad Nacional Autónoma de México), Steve Horvath(University of California, Los Angeles)
Nature Communications
March 12, 2021
10.1038/s41467-021-21900-2
Cited by 167Open Access
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Abstract

Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.

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