Identification of key pathways and metabolic fingerprints of longevity in C. elegans

Abstract

Impaired insulin/IGF-1 signaling (IIS) pathway and caloric restriction (CR) are two well-established interventions to prolong lifespan in worm C. elegans. However, a cross comparison of these longevity pathways using a multi-omics integration approach is lacking. In this study, we aimed to identify key pathways and metabolite fingerprints of longevity that are shared between IIS and CR worm models using a multi-omics integration approach. We generated transcriptomics and metabolomics data from two long-lived mutant worm strains, i.e. daf-2 (impaired IIS pathway) and eat-2 (CR model) and compared them with the N2 strain. Transcriptional profiling identified shared longevity signatures between the two strains, such as an upregulation of lipid storage and defense responses and downregulation of macromolecule synthesis and developmental processes. The shared longevity signatures revealed by metabolomics profiling included an increase in the levels of glycerol-3P, ademine, xanthine, and AMP, and a decrease in the levels of the amino acid pool, the C18:0 and C17:1 fatty acids. After we integrated transcriptomics and metabolomics data based on the annotations in KEGG, our results highlighted a downregulation of pyrimidine metabolism and upregulation of purine metabolism as a commonality between the two longevity mechanisms. Overall, our findings point towards the existence of shared metabolic pathways that are likely important for lifespan extension and provide novel insights into potential regulators and metabolic fingerprints for longevity.