Data from: Evolution of longevity improves immunity in Drosophila

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 Drosophila melanogaster 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 Toll receptor extended lifespan,
whereas silencing the pathway antagonist cactus – 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.