CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics

Abstract

The overarching aim of this proposal is to delineate the common molecular networks in adipose tissue involved in the lifespan and health promoting effects of dietary restriction and its mimetics such as dietary Methionine Restriction (MR) and dietary supplementation with Nicotinamide Riboside (NR) - a dairy constituent that maintains NAD metabolism. To achieve that, we designed a pipeline to sort out biologically relevant pathways affected by these interventions. Briefly, we will perform omics of samples obtained from C. elegans, and adipose tissue and serum of mice and humans (healthy and/or type 2 diabetic) subjected to DR or its mimetic interventions. We will correlate these findings with lifespan and/or metabolic profiling and use bioinformatics tools to identify evolutionary conserved pathways that are commonly affected by the dietary interventions. The relevant pathways will then be scrutinized using gain- or loss-of-function models in C. elegans, mice and mammalian preadipocyte cell lines, providing new insights into how these dietary interventions affect health span in multiple organisms, including humans. (AU)