Genome Methylation Predicts Age and Longevity of Bats

Bats hold considerable potential for understanding exceptional longevity because some species can live eight times longer than other mammals of similar size [1]. Estimating their age or longevity is difficult because they show few signs of aging. DNA methylation (DNAm) provides a potential solution given its utility for estimating age [2-4] and lifespan [5-7] in humans. Here, we profile DNAm from wing biopsies of nearly 700 individuals representing 26 bat species and demonstrate that DNAm can predict chronological age accurately. Furthermore, the rate DNAm changes at age-informative sites is negatively related to longevity. To identify longevity-informative sites, we compared DNAm rates between three long-lived and two short-lived species. Hypermethylated age and longevity sites are enriched for histone and chromatin features associated with transcriptional regulation and preferentially located in the promoter regions of helix-turn-helix transcription factors (TFs). 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, in part, from augmented immune response and cancer suppression.