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

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

Wilkinson GS; Adams DM; Haghani A; Lu AT; Zoller J; Breeze CE; Arnold BD; Ball HC; Carter GG; Cooper LN; Dechmann DKN; Devanna P; Fasel NJ; Galazyuk AV; Günther L; Hurme E; Jones G; Knörnschild M; Lattenkamp EZ; Li CZ; Mayer F; Reinhardt JA; Medellin RA; Nagy M; Pope B; Power ML; Ransome RD; Teeling EC; Vernes Sonja C; Zamora-Mejías D; Zhang J; Faure PA; Greville LJ; Horvath S

Nature Communications

2021

2021-03-12

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.

Journal Article

12

NEOMED College of Medicine

Department of Anatomy & Neurobiology

Jan to Aug list 2021