Open AccessRegulation of longevity by regulator of G‐protein signaling protein, Loco
Author(s) -
Lin YuhRu,
Kim Keetae,
Yang Yanfei,
Ivessa Andreas,
Sadoshima Junichi,
Park Yongkyu
Publication year - 2011
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/j.1474-9726.2011.00678.x
Subject(s) - biology , longevity , gtpase activating protein , rgs2 , signal transduction , g protein , drosophila melanogaster , microbiology and biotechnology , regulation of gene expression , gene , genetics
Summary Regulator of G‐protein signaling (RGS) proteins contribute to G‐protein signaling pathways as activators or repressors with GTPase‐activating protein (GAP) activity. To characterize whether regulation of RGS proteins influences longevity in several species, we measured stress responses and lifespan of RGS‐overexpressing and RGS‐lacking mutants. Reduced expression of Loco, a RGS protein of Drosophila melanogaster , resulted in a longer lifespan for both male and female flies, also exhibiting stronger resistance to three different stressors (starvation, oxidation, and heat) and higher manganese‐containing superoxide dismutase (MnSOD) activity. In addition, this reduction in Loco expression increased fat content and diminished cAMP levels. In contrast, overexpression of both genomic and cDNA loco gene significantly shortened the lifespan with weaker stress resistance and lower fat content. Deletion analysis of the Loco demonstrated that its RGS domain is required for the regulation of longevity. Consistently, when expression of RGS14, mammalian homologue of Loco, was reduced in rat fibroblast cells, the resistance to oxidative stress increased with higher MnSOD expression. The changes of yeast Rgs2 expression, which shares a conserved RGS domain with the fly Loco protein, also altered lifespan and stress resistance in Saccharomyces cerevisiae . Here, we provide the first evidence that RGS proteins with GAP activity affect both stress resistance and longevity in several species.