Unravelling Extended Longevity Mechanism in Bats: Insights From Life-History Traits and Comparative Genomics

Chiroptera species (hereafter bats) exhibit extraordinarily long lifespans compared to non-flying mammals of similar body size, yet the underlying ecological drivers and molecular mechanisms remain poorly understood. In this study, we employed phylogenetic regression models to explain maximum longevity (MLg) variation using 24 life-history traits from 101 bat species. In parallel, we conducted comprehensive comparative genomics analyses on 39 high-quality bat genomes to identify candidate genes and biological processes involved in longevity regulation. Our results revealed that female age at sexual maturity and maximum latitude explain the greatest proportion of MLg variation within bats, and genes involved in DNA damage repair, inflammation, immunity and mitochondrial function may play critical roles in various extremely long-lived bat species. We also identified the potential importance of lipid metabolism, specifically the cholesterol metabolism pathway and APO gene family, as a previously under-appreciated mechanism in bat longevity regulation. Given the distinct ecological and physiological features, our family-specific analyses on Vespertilionidae and Pteropodidae uncovered divergent life-history predictors and genetic strategies for extended longevity. In Vespertilionidae, MLg is most strongly associated with latitude and may be regulated primarily through the maintenance of DNA stability, while MLg in Pteropodidae is best predicted by body mass and is linked to tumour suppression and immune response. Overall, our study elucidates the complex interplay between life-history factors and genomic adaptations underlying extended lifespans in bats, providing valuable insights into mammalian longevity evolution and potential targets for improving human healthspan.