| Title: | Pheromone sensing regulates Caenorhabditis elegans lifespan and stress resistance via the deacetylase SIR-2.1 |
| Author(s): | Ludewig AH; Izrayelit Y; Park D; Malik RU; Zimmermann A; Mahanti P; Fox BW; Bethke A; Doering F; Riddle DL; Schroeder FC; |
| Address: | "Boyce Thompson Institute, and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA" |
| ISSN/ISBN: | 1091-6490 (Electronic) 0027-8424 (Print) 0027-8424 (Linking) |
| Abstract: | "Lifespan in Caenorhabditis elegans, Drosophila, and mice is regulated by conserved signaling networks, including the insulin/insulin-like growth factor 1 (IGF-1) signaling cascade and pathways depending on sirtuins, a family of NAD(+)-dependent deacetylases. Small molecules such as resveratrol are of great interest because they increase lifespan in many species in a sirtuin-dependent manner. However, no endogenous small molecules that regulate lifespan via sirtuins have been identified, and the mechanisms underlying sirtuin-dependent longevity are not well understood. Here, we show that in C. elegans, two endogenously produced small molecules, the dauer-inducing ascarosides ascr#2 and ascr#3, regulate lifespan and stress resistance through chemosensory pathways and the sirtuin SIR-2.1. Ascarosides extend adult lifespan and stress resistance without reducing fecundity or feeding rate, and these effects are reduced or abolished when nutrients are restricted. We found that ascaroside-mediated longevity is fully abolished by loss of SIR-2.1 and that the effect of ascr#2 requires expression of the G protein-coupled receptor DAF-37 in specific chemosensory neurons. In contrast to many other lifespan-modulating factors, ascaroside-mediated lifespan increases do not require insulin signaling via the FOXO homolog DAF-16 or the insulin/IGF-1-receptor homolog DAF-2. Our study demonstrates that C. elegans produces specific small molecules to control adult lifespan in a sirtuin-dependent manner, supporting the hypothesis that endogenous regulation of metazoan lifespan functions, in part, via sirtuins. These findings strengthen the link between chemosensory inputs and conserved mechanisms of lifespan regulation in metazoans and suggest a model for communal lifespan regulation in C. elegans" |
| Keywords: | "Animals Caenorhabditis elegans/metabolism/*physiology Caenorhabditis elegans Proteins/*metabolism Floxuridine Glycolipids/*metabolism Longevity/*physiology Oxidative Stress/physiology Receptors, G-Protein-Coupled/metabolism Sirtuins/*metabolism Stress, Ph;" |
| Notes: | "MedlineLudewig, Andreas H Izrayelit, Yevgeniy Park, Donha Malik, Rabia U Zimmermann, Anna Mahanti, Parag Fox, Bennett W Bethke, Axel Doering, Frank Riddle, Donald L Schroeder, Frank C eng AG033839/AG/NIA NIH HHS/ R21 AG033839/AG/NIA NIH HHS/ T32 GM008500/GM/NIGMS NIH HHS/ T32GM008500/GM/NIGMS NIH HHS/ GM088290/GM/NIGMS NIH HHS/ R01 GM088290/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural 2013/03/20 Proc Natl Acad Sci U S A. 2013 Apr 2; 110(14):5522-7. doi: 10.1073/pnas.1214467110. Epub 2013 Mar 18" |
