Genome-Wide Analyses for Lifespan and Healthspan in D. Melanogaster Reveal Decima as a Regulator of Insulin-Like Peptide Production

Dietary restriction (DR) extends lifespan and delays age-related diseases across species. An underlying assumption in the aging field is that DR extends both lifespan and healthspan through similar mechanisms, but this has not been rigorously tested in different genetic backgrounds. Furthermore, nutrient response genes responsible for lifespan or healthspan extension remain underexplored in natural populations. To address this, we measured nutrient-dependent changes in lifespan and age-related climbing ability, a measure of healthspan, in the DGRP strains. DR generally extended lifespan and delayed decline in climbing ability, but there was a lack of correlation between these traits across individual strains. We then identified and validated decima as a lifespan determinant and Daedalus for climbing. We found that decima regulates insulin-like peptide transcription in the GABA receptor neurons through sNPF signaling. Modulating these genes produced independent effects on lifespan and climbing, which suggests that these age-related traits are regulated through distinct mechanisms.