The role of ATGL-1 in CeTOR regulated longevity in C. elegans

Abstract

Aging is a major risk factor for many chronic diseases and a complex biological phenomenon. The most well studied and characterized pathways involved in metabolism and known to regulate longevity include sirtuins, AMP-activated protein kinase, insulin-like growth factor (IGF) and the mechanistic target of rapamycin (mTOR).1 These signaling pathways and related transcriptional factors are evolutionarily conserved from yeast to primates. Evidence suggests adipose tissue plays an important role in the regulation of lifespan particularly through energy homeostasis during times of scarcity and excess. Our laboratory has shown adipose triglyceride lipase (ATGL), the rate-limiting enzyme within the lipolytic pathway, is the target of dietary restriction and insulin/IGF-1 signaling pathways, both of which regulate lifespan.22 Given the convergence and necessity of ATGL-1 in the longevity response of dietary restriction and reduced insulin/IGF1 signaling pathways and the uncertainty of the downstream effects TOR has on longevity, we hypothesize that ATGL-1 plays an important role in CeTOR regulated longevity in C. elegans. This investigation was carried out by (a) determining whether levels of ATGL-1 are influenced by TOR inhibition via rapamycin and TOR specific RNA interference (RNAi) and (b) examining the role of ATGL-1 in CeTOR regulated longevity in C. elegans. We have found that rapamycin treatment does not increase expression of ATGL-1::GFP in C. elegans, however, continued research with CeTOR inhibition using rapamycin and RNAi treatment is necessary. The RNAi and longevity experiments need to be conducted. Tissue specific regulation of ATGL expression has been shown to be implicated in chronic disease and in longevity. However, there are still many insights to be discovered and understood about its role in longevity pathways, including feedback mechanisms and second messengers lipolytic products play. Elucidating the downstream effects of ATGL within model organisms will impact future chronic disease research and longevity studies. Given that these pathways are widely evolutionarily conserved, future findings will aid in understanding longevity regulatory mechanisms in humans.