Journal
NATURE ECOLOGY & EVOLUTION
Volume 3, Issue 7, Pages 1110-1120Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41559-019-0913-3
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Funding
- Irish Centre for High-End Computing
- 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
- China Scholarship Council studentship (under the UCD-CSC funding programme)
- Contrat Nature Grant
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Bats are the longest-lived mammals, given their body size. However, the underlying molecular mechanisms of their extended healthspans are poorly understood. To address this question we carried out an eight-year longitudinal study of ageing in long-lived bats (Myotis myotis). We deep-sequenced similar to 1.7 trillion base pairs of RNA from 150 blood samples collected from known aged bats to ascertain the age-related transcriptomic shifts and potential microRNA-directed regulation that occurred. We also compared ageing transcriptomic profiles between bats and other mammals by analysis of 298 longitudinal RNA sequencing datasets. Bats did not show the same transcriptomic changes with age as commonly observed in humans and other mammals, but rather exhibited a unique, age-related gene expression pattern associated with DNA repair, autophagy, immunity and tumour suppression that may drive their extended healthspans. We show that bats have naturally evolved transcriptomic signatures that are known to extend lifespan in model organisms, and identify novel genes not yet implicated in healthy ageing. We further show that bats' longevity profiles are partially regulated by microRNA, thus providing novel regulatory targets and pathways for future ageing intervention studies. These results further disentangle the ageing process by highlighting which ageing pathways contribute most to healthy ageing in mammals.
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