Dietary restriction is evolutionarily conserved on the phenotypic and mechanistic level

The anti-ageing response to Dietary Restriction (DR) is thought to be mechanistically ancient, reasoning from its phenotypic conservation. However, DR is implemented differently across species and evidence for conserved mechanisms remains limited. Here, we tested longevity and fecundity in response to DR across eight different Drosophila species, finding that DR is, on balance, phenotypically conserved. Next, we used comparative transcriptomics and found strongly concordant responses to DR. We studied the evolutionary history of the top concordantly differentially expressed orthologous genes and identified that many are "young" genes, suggesting that the genetic basis of DR is not widely conserved. To validate this hypothesis, we tested the longevity effects of the 15 most conserved genes that change in transcription in response to DR. Surprisingly, we found that 12 out of 15 genes tested had a lifespan phenotype, with 9 extending lifespan. Our findings suggest that while large parts of the DR response are taxonomically specific, some core mechanisms appear conserved. The comparative approaches we used here hold promise to identify shared mechanisms relevant to our own species.