Summary
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.
Competing Interest Statement
The authors have declared no competing interest.
