Evolution of longevity improves immunity inDrosophila

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 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.

Distinct genomic signals of lifespan and life history evolution in response to postponed reproduction and larval diet inDrosophila

“…; Fabian et al. ; Flatt and Partridge ), we only found a few loci in this signaling network among our candidates. For instance, among the loci significantly differentiated between the E and P populations, we identified the TOR signaling gene happyhour (Bryk et al.…”

“…() and Fabian et al. () was higher than expected by chance ( P < 0.0014; Bonferroni correction: 0.05/43 intersections). Significant overlaps of the different intersections are indicated by shades of red.…”

“…() ( P = 3.5 × 10 −6 ) and Fabian et al. () ( P = 2.6 × 10 −10 ), but not with the dataset of Remolina et al. () ( P = 0.96).…”

“…; Fabian et al. ). Similar to ours, these studies found only weak support for an involvement of loci in the IIS/TOR or other major longevity pathways in the evolution of longevity (Table ).…”

“…; Fabian et al. ; see Supporting Information Methods for additional information on these E&R studies). Notably, at the candidate gene level (but not at the SNP level), we identified a significant overlap with the datasets of Carnes et al.…”