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.

中文翻译：

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通过 G 蛋白信号蛋白 Loco 的调节器调节寿命。

G 蛋白信号传导 (RGS) 蛋白的调节剂作为具有 GTP 酶激活蛋白 (GAP) 活性的激活剂或阻遏物参与 G 蛋白信号传导途径。为了表征 RGS 蛋白的调节是否影响多个物种的寿命，我们测量了 RGS 过表达和 RGS 缺失突变体的应激反应和寿命。黑腹果蝇的一种 RGS 蛋白 Loco 的表达降低，导致雄性和雌性果蝇的寿命更长，并且对三种不同的压力因素（饥饿、氧化和热）和更高的含锰超氧化物歧化酶 (MnSOD) 表现出更强的抵抗力活动。此外，Loco 表达的这种减少增加了脂肪含量并降低了 cAMP 水平。与此相反，这两个基因组和cDNA的过量表达机车基因显着缩短寿命，抗逆性较弱，脂肪含量较低。Loco 的缺失分析表明，其 RGS 域是调节寿命所必需的。一致地，当大鼠成纤维细胞中 Loco 的哺乳动物同源物 RGS14 的表达降低时，对氧化应激的抵抗力随着 MnSOD 表达的升高而增加。酵母 Rgs2 表达的变化与果蝇 Loco 蛋白共享一个保守的 RGS 结构域，也改变了酿酒酵母的寿命和抗逆性。在这里，我们提供了第一个证据，证明具有 GAP 活性的 RGS 蛋白会影响几个物种的抗逆性和寿命。