Journal
AGING-US
Volume 13, Issue 6, Pages 7998-8025Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.202852
Keywords
autophagy; bats; aging; blood mRNA; phylogenomics
Categories
Funding
- European Research Council Research Grant [ERC-2012-StG311000]
- UCD Wellcome Institutional Strategic Support Fund - University College Dublin [204844/Z/16/Z]
- UCD Wellcome Institutional Strategic Support Fund - SFI-HRB-Wellcome Biomedical Research Partnership [204844/Z/16/Z]
- Irish Research Council Consolidator Laureate Award
- UCD School of Biology studentship
- US National Institutes of Health
- Contrat Nature Grant
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Research shows that in bats, the expression of autophagy-related genes increases with age, a phenomenon not commonly seen in other mammals. By analyzing the bat genome, key genes that influence the increase in autophagy signaling have been identified, which may contribute to extending the bats' healthspan.
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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