Evolution of mammalian longevity: age-related increase in autophagy in bats compared to other mammals

哺乳动物寿命的进化:与其他哺乳动物相比,蝙蝠的自噬随年龄增加

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作者:Joanna Kacprzyk, Andrea G Locatelli, Graham M Hughes, Zixia Huang, Michael Clarke, Vera Gorbunova, Carlotta Sacchi, Gavin S Stewart, Emma C Teeling

Abstract

Autophagy maintains cellular homeostasis and its dysfunction has been implicated in aging. Bats are the longest-lived mammals for their size, but the molecular mechanisms underlying their extended healthspan are not well understood. Here, drawing on >8 years of mark-recapture field studies, we report the first longitudinal analysis of autophagy regulation in bats. Mining of published population level aging blood transcriptomes (M. myotis, mouse and human) highlighted a unique increase of autophagy related transcripts with age in bats, but not in other mammals. This bat-specific increase in autophagy transcripts was recapitulated by the western blot determination of the autophagy marker, LC3II/I ratio, in skin primary fibroblasts (Myotis myotis,Pipistrellus kuhlii, mouse), that also showed an increase with age in both bat species. Further phylogenomic selection pressure analyses across eutherian mammals (n=70 taxa; 274 genes) uncovered 10 autophagy-associated genes under selective pressure in bat lineages. These molecular adaptations potentially mediate the exceptional age-related increase of autophagy signalling in bats, which may contribute to their longer healthspans.

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