Computer prediction and genetic analysis identifies retinoic acid modulation as a driver of conserved longevity pathways in genetically-diverse Caenorhabditis nematodes.

We present a survey of longevity effects for compounds suggested by a previously published computational prediction set using the comprehensive, multi-species approach utilized by the Caenorhabditis Intervention Testing Program (CITP). The compound all-trans retinoic acid extended lifespan in the nematode Caenorhabditis elegans. Given the dependency of lifespan extension under atRA treatment, we used RNA-seq to assess transcriptional changes under atRA treatment in wildtype N2 animals. In order to further dissect transcriptional response in detail, we repeated our transcriptional analysis in hsf-1(sy441) and aak-2(ok524) mutants. Overall design: We performed differential gene expression analysis comparing atRA-treated and DMSO control samples (4 biological replicates each) in 4 day old adult worms in the wildtype N2, PS3551 [hsf-1(sy411)], and RB754 [aak-2(ok524)] strains.