Are you cuckoo for clocks, dotty for DNA methylation, and avid about aging? Well, a “batty” new study of epigenetic aging in certain long-lived winged mammals has just added to the zoo of clues about epigenetic age by providing a bat epigenetic clock.
Specifically, an ardent team of researchers led by the levels heads of Gerald S. Wilkinson (University of Maryland) and Steve Horvath (University of California, Los Angeles) sought to develop an epigenetic clock to predict aging and analyze longevity in various species of bats. As certain species display maximum lifespans over four times greater than similar-sized mammals, with fewer signs of aging, figuring out just why some species differ in lifespan could reveal the epigenetic fountain of youth. To learn more, the team used a custom array of 37,492 conserved CpG sites, known as the HorvathMammalMethylChip40, to generate DNA methylation profiles from 712 wing tissue biopsies of known-age bats from twenty-six species to identify those changes associated with age and longevity.
So let’s hear all the details on the new bat epigenetic clock from the study from Wilkinson and colleagues:
- Elastic-net regression predicts the chronological age of bats with high accuracy from a linear combination of DNA methylation values (DNAmAge) using 162 CpG sites (similar to human epigenetic clocks)
- A DNA methylation analysis from a wing biopsy reveals an animal’s age to within a year
- Analysis of cross-species DNA methylation kinetics at age-associated sites suggests that better epigenetic maintenance (low rate of change) associates with a longer maximum lifespan, independent of body size
- The hypermethylated sites associated with age and longevity, which are generally distinct, locate to the promoter regions of crucial transcription factors involved in developmental processes
- Furthermore, these developmental processes influence age-related methylation kinetics
- DNA methylation changes linked to longevity impact genes associate with innate immunity or tumorigenesis, suggesting that augmented immune responses and inhibited tumorigenic pathways support healthy aging
Overall, this definitely not daffy description of a DNA methylation-based epigenetic clock for bats has allowed the authors to propose epigenetic stability at genes supporting innate immunity and suppressing tumorigenesis as one of the main reasons behind the observed exceptional longevity in bats.
Regarding the relevance of this research to a better understanding of the causes for age-related declines across many species, co-first author Gerald S. Wilkinson added: “Bats live a long time, and yet their hearing doesn’t decay with age, the way ours does. You could use this method to see whether there are differences in methylation that are associated with hearing. There are all kinds of questions like this we can ask now.”
See how echolocation might just lead us to the epigenetic clock controlling the fountain of youth over at Nature Communications, March 2021.