Evolution of longevity improves immunity in <i>Drosophila</i>.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_EB38605C9A56
Type
Article: article from journal or magazin.
Collection
Publications
Title
Evolution of longevity improves immunity in <i>Drosophila</i>.
Journal
Evolution Letters
Author(s)
Fabian D.K., Garschall K., Klepsatel P., Santos-Matos G., Sucena É., Kapun M., Lemaitre B., Schlötterer C., Arking R., Flatt T.
ISSN
2056-3744 (Electronic)
ISSN-L
2056-3744
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
2
Number
6
Pages
567-579
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Much has been learned about the genetics of aging from studies in model organisms, but still little is known about naturally occurring alleles that contribute to variation in longevity. For example, analysis of mutants and transgenes has identified insulin signaling as a major regulator of longevity, yet whether standing variation in this pathway underlies microevolutionary changes in lifespan and correlated fitness traits remains largely unclear. Here, we have analyzed the genomes of a set of <i>Drosophila melanogaster</i> lines that have been maintained under direct selection for postponed reproduction and indirect selection for longevity, relative to unselected control lines, for over 35 years. We identified many candidate loci shaped by selection for longevity and late-life fertility, but - contrary to expectation - we did not find overrepresentation of canonical longevity genes. Instead, we found an enrichment of immunity genes, particularly in the Toll pathway, suggesting that evolutionary changes in immune function might underpin - in part - the evolution of late-life fertility and longevity. To test whether this genomic signature is causative, we performed functional experiments. In contrast to control flies, long-lived flies tended to downregulate the expression of antimicrobial peptides upon infection with age yet survived fungal, bacterial, and viral infections significantly better, consistent with alleviated immunosenescence. To examine whether genes of the Toll pathway directly affect longevity, we employed conditional knockdown using in vivo RNAi. In adults, RNAi against the <i>Toll</i> receptor extended lifespan, whereas silencing the pathway antagonist <i>cactus</i> --causing immune hyperactivation - dramatically shortened lifespan. Together, our results suggest that genetic changes in the age-dependent regulation of immune homeostasis might contribute to the evolution of longer life.
Keywords
Aging, Drosophila, evolve, immunity, longevity, resequence
Pubmed
Web of science
Open Access
Yes
Create date
14/01/2019 18:19
Last modification date
20/08/2019 17:13
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