Dietary restriction is evolutionary conserved on the phenotypic and mechanistic level

The anti-ageing response of Dietary Restriction (DR) is thought to be an ancient mechanistic response, reasoning from its phenotypic conservation in a wide range of organisms. However, DR is implemented using different diets and methods across species, and evidence for conservation at the mechanistic level remains limited. Here we tested the longevity and fecundity response to DR across eight different species of Drosophila using the same diets in a reaction norm framework. We confirm that DR is phenotypically conserved across Drosophila. Next, we used comparative transcriptomics across six species and found strongly concordant differential expression in response to DR (rs > 0.28, < 0.72, P < 0.0001). We studied the evolutionary history of the top concordantly differentially expressed orthologous genes and identified that the large majority of these genes are "young" genes and are Diptera specific. Our results indicate that large parts of the DR response are likely to be taxonomic specific, suggesting that the genetic basis of DR is not widely conserved. To validate this hypothesis we tested whether the 15 most conserved genes that change in transcription in response to DR using conditional in vivo RNAi. Surprisingly, we found that 12 out of 15 genes tested had a lifespan phenotype, with 9 extending lifespan. Five of these genes are related to cysteine metabolism implicating it in the mechanisms of DR, further suggesting physiological compensation to DR is ubiquitous and providing a possible biomedical target. Our findings suggest that while large parts of the DR response are taxonomically specific, some core mechanisms are conserved across divergent species. The comparative approaches we used here hold promise to identify shared mechanisms relevant to our own species and therefore ultimately anti-ageing interventions.