ATGL-1 mediates the effect of dietary restriction and the insulin/IGF-1 signaling pathway on longevity in C.?elegans

摘要

Objective Animal lifespan is controlled through genetic pathways that are conserved from nematodes to humans. Lifespan-promoting conditions in nematodes include fasting and a reduction of insulin/IGF signaling. Here we aimed to investigate the input of the Caenorhabditis elegans homologue of the mammalian rate-limiting lipolytic enzyme Adipose Triglyceride Lipase, ATGL-1, in longevity control. Methods We used a combination of genetic and biochemical approaches to determine the role of ATGL-1 in accumulation of triglycerides and regulation of longevity. Results We found that expression of ATGL is increased in the insulin receptor homologue mutant daf-2 in a FoxO/DAF-16-dependent manner. ATGL-1 is also up-regulated by fasting and in the eat-2 loss-of-function mutant strain. Overexpression of ATGL-1 increases basal and maximal oxygen consumption rate and extends lifespan in C.?elegans . Reduction of ATGL-1 function suppresses longevity of the long-lived mutants eat-2 and daf-2 . Conclusion Our results demonstrate that ATGL is required for extended lifespan downstream of both dietary restriction and reduced insulin/IGF signaling.