Open AccessChemical activation of a food deprivation signal extends lifespan
Author(s) -
Lucanic Mark,
Garrett Theo,
Yu Ivan,
Calahorro Fernando,
Asadi Shahmirzadi Azar,
Miller Aaron,
Gill Matthew S.,
Hughes Robert E.,
HoldenDye Lindy,
Lithgow Gordon J.
Publication year - 2016
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12492
Subject(s) - biology , caenorhabditis elegans , sensory system , glutamate receptor , signal transduction , model organism , neuroscience , computational biology , genetics , gene , receptor
Summary Model organisms subject to dietary restriction ( DR ) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on multiple metrics. This indicates that pharmacological treatments that mimic the effects of DR could improve health in humans. To find new chemical structures that extend lifespan, we screened 30 000 synthetic, diverse drug‐like chemicals in Caenorhabditis elegans and identified several structurally related compounds that acted through DR mechanisms. The most potent of these NP 1 impinges upon a food perception pathway by promoting glutamate signaling in the pharynx. This results in the overriding of a GPCR pathway involved in the perception of food and which normally acts to decrease glutamate signals. Our results describe the activation of a dietary restriction response through the pharmacological masking of a novel sensory pathway that signals the presence of food. This suggests that primary sensory pathways may represent novel targets for human pharmacology.