Effect of Pro-longevity drugs on Lipid profile, link between lipid signalling and longevity

We report the effect of four lifespan modifying drugs and of combinations of these drugs on lipid profile in Caenorhabditis elegans. We investigated drug-drug interactions and identified beneficial drug interactions between drugs selected to target synergistic longevity mechanisms and pathways. We employ ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) to compare the abundance of lipid species in treated and control animals. Adult nematodes were treated with rapamycin, rifampicin, psora-4 and allantoin and combinations of these compounds and the resulting change in lipid profiles, specifically in those of triacylglycerol (TAG), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were determined. We quantified changes resulting from treatment with the drug combinations relative to untreated controls and relative to animals treated with each constituent single drugs. We further determined the dependence of changes in lipid profiles on genes know to affect lipid metabolism using strains carrying mutations in these pathways. In particular, we determined lipid profiles in genetic model of caloric restriction (eat-2), strain lacking homolog of TGFβ (daf-7) and in strain lacking the SREBP/sbp-1 transcription factor.