Big brown bats experience slower epigenetic ageing during hibernation

Abstract

Comparative analyses of bats indicate that hibernation is associated with increased longevity among species. However, it is not yet known if hibernation affects biological ageing of individuals. Here, we use DNA methylation (DNAm) as an epigenetic biomarker of ageing to determine the effect of hibernation on the big brown bat, Eptesicus fuscus . First, we compare epigenetic age, as predicted by a multi-species epigenetic clock, between hibernating and non-hibernating animals and find that hibernation is associated with epigenetic age. Second, we identify genomic sites that exhibit hibernation-associated change in DNAm, independent of age, by comparing samples taken from the same individual in hibernating and active seasons. This paired comparison identified over 3000 differentially methylated positions (DMPs) in the genome. Genome-wide association comparisons to tissue-specific functional elements reveals that DMPs with elevated DNAm during winter occur at sites enriched for quiescent chromatin states, whereas DMPs with reduced DNAm during winter occur at sites enriched for transcription enhancers. Furthermore, genes nearest DMPs are involved in regulation of metabolic processes and innate immunity. Finally, significant overlap exists between genes nearest hibernation DMPs and genes nearest previously identified longevity DMPs. Taken together, these results are consistent with hibernation influencing ageing and longevity in bats.

Age estimation based on blood DNA methylation levels in brown bears

“…In general, hibernators live longer than similar-sized non-hibernators (Wilkinson & South 2002;Turbill et al 2011;Wilkinson and Adams 2019). Recent studies of yellow-bellied marmots, Marmota flaviventris , (Pinho et al 2022) and big brown bats, Eptesicus fuscu s, (Sullivan et al 2022) suggest that this difference arises in part because hibernation slows epigenetic aging. Similarly, in bears, the low metabolic state characteristic of hibernation (Tøien et al 2011) may reduce the rate of DNA methylation changes, lowering the epigenetic ages of aged individuals.…”

Age estimation based on blood DNA methylation levels in brown bears

“…Factors linked to lifestyle, including obesity, weight reduction, and overfeeding, have been suggested to affect DNA methylation (Samblas et al, 2019;Yamazaki et al, 2021) Wilkinson & South, 2002). Recent studies of yellow-bellied marmots, Marmota flaviventris, (Pinho et al, 2022) and big brown bats, Eptesicus fuscus, (Sullivan et al, 2022) suggest that this difference arises in part because hibernation slows epigenetic aging. Similarly, in bears, the low metabolic state characteristic of hibernation (Tøien et al, 2011) may reduce the rate of DNA methylation changes, lowering the epigenetic ages of aged individuals.…”

Epigenetic age estimation of wild mice using faecal samples

“…Such epigenetic clocks can provide a more accurate estimate of chronological age among wild animals than visible characteristics (Larison et al., 2021; Mayne et al., 2022). Epigenetic clocks have now been developed for a wide range of animal species including baboons, chimpanzees, humpback whales, wolves, green turtles and zebras (Anderson et al., 2021; Bors et al., 2021; De Paoli‐Iseppi et al., 2017; Fairfield et al., 2021; Ito et al., 2018; Jarman et al., 2015; Larison et al., 2021; Mayne et al., 2022; Pinho et al., 2022; Polanowski et al., 2014; Sullivan et al., 2022; Tangili et al., 2023; Thompson et al., 2017; Wilkinson et al., 2021; Wright et al., 2018), as well as plants (Gardner et al., 2023).…”

“…Insights have also come from the wild: high social rank is associated with accelerated epigenetic ageing in wild baboons (Anderson et al, 2021), and hibernation slows down ageing in marmots and bats (Pinho et al, 2022;Sullivan et al, 2022). Thus, the use of epigenetic clocks may provide a means of estimating chronological age among wild animals while simultaneously providing insight into biological ageing in natural settings.…”