TY - JOUR
T1 - DNA methylation predicts age and provides insight into exceptional longevity of bats
AU - Wilkinson, Gerald S.
AU - Adams, Danielle M.
AU - Haghani, Amin
AU - Lu, Ake T.
AU - Zoller, Joseph
AU - Breeze, Charles E.
AU - Arnold, Bryan D.
AU - Ball, Hope C.
AU - Carter, Gerald G.
AU - Cooper, Lisa Noelle
AU - Dechmann, Dina K.N.
AU - Devanna, Paolo
AU - Fasel, Nicolas J.
AU - Galazyuk, Alexander V.
AU - Günther, Linus
AU - Hurme, Edward
AU - Jones, Gareth
AU - Knörnschild, Mirjam
AU - Lattenkamp, Ella Z.
AU - Li, Caesar Z.
AU - Mayer, Frieder
AU - Reinhardt, Josephine A.
AU - Medellin, Rodrigo A.
AU - Nagy, Martina
AU - Pope, Brian
AU - Power, Megan L.
AU - Ransome, Roger D.
AU - Teeling, Emma C.
AU - Vernes, Sonja C.
AU - Zamora-Mejías, Daniel
AU - Zhang, Joshua
AU - Faure, Paul A.
AU - Greville, Lucas J.
AU - Horvath, Steve
PY - 2021/3/12
Y1 - 2021/3/12
N2 - 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.
AB - 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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U2 - 10.1038/s41467-021-21900-2
DO - 10.1038/s41467-021-21900-2
M3 - Article
C2 - 33712580
AN - SCOPUS:85102504493
SN - 2041-1723
VL - 12
SP - 1615
JO - Nature communications
JF - Nature communications
IS - 1
ER -