Epigenetic Aging Slows During Hiberation in a Common Bat Species

This open access paper on epigenetic age and hibernation in bats makes an interesting companion piece to similar research into marmots from earlier in the year. It seems that hibernation may slow epigenetic aging in a range of species, though it may not be enough to explain differences in life span between all similar hibernating and non-hibernating species. Nonetheless, researchers have for some years shown interest in the biochemistry of hibernation in the context of aging. It remains to be seen what there is to learn here, and whether it can form the basis for therapies or enhancements in human medicine.

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.

In conclusion, application of a multi-species bat epigenetic clock provides strong evidence that hibernation is associated with slower epigenetic ageing. The multi-species clock explains 94% of the variation in the chronological ages of both hibernating and non-hibernating big brown bats; however, the clock estimates are equal to or greater than the chronological age, suggesting big brown bats age slightly faster than a 'typical' bat, especially during the active period.

Link: https://doi.org/10.1098/rspb.2022.0635

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