Pro-aging effects of glucose signaling through a G protein-coupled glucose receptor in fission yeast.
Pro-aging effects of glucose signaling through a G protein-coupled glucose receptor in fission yeast.
复制标题
DOI：
10.1371/journal.pgen.1000408
复制
发表时间：
2009-03
期刊：
影响因子：
4.5
通讯作者：
Rokeach LA
中科院分区：
文献类型：
--
作者：
Roux AE;Leroux A;Alaamery MA;Hoffman CS;Chartrand P;Ferbeyre G;Rokeach LA
Glucose is the preferred carbon and energy source in prokaryotes, unicellular eukaryotes, and metazoans. However, excess of glucose has been associated with several diseases, including diabetes and the less understood process of aging. On the contrary, limiting glucose (i.e., calorie restriction) slows aging and age-related diseases in most species. Understanding the mechanism by which glucose limits life span is therefore important for any attempt to control aging and age-related diseases. Here, we use the yeast Schizosaccharomyces pombe as a model to study the regulation of chronological life span by glucose. Growth of S. pombe at a reduced concentration of glucose increased life span and oxidative stress resistance as reported before for many other organisms. Surprisingly, loss of the Git3 glucose receptor, a G protein-coupled receptor, also increased life span in conditions where glucose consumption was not affected. These results suggest a role for glucose-signaling pathways in life span regulation. In agreement, constitutive activation of the Gα subunit acting downstream of Git3 accelerated aging in S. pombe and inhibited the effects of calorie restriction. A similar pro-aging effect of glucose was documented in mutants of hexokinase, which cannot metabolize glucose and, therefore, are exposed to constitutive glucose signaling. The pro-aging effect of glucose signaling on life span correlated with an increase in reactive oxygen species and a decrease in oxidative stress resistance and respiration rate. Likewise, the anti-aging effect of both calorie restriction and the Δgit3 mutation was accompanied by increased respiration and lower reactive oxygen species production. Altogether, our data suggest an important role for glucose signaling through the Git3/PKA pathway to regulate S. pombe life span. Lowering caloric intake by limiting glucose (the preferred carbon and energy source) increases life span in various species. Excess glucose can have deleterious effects, but it is not clear whether this is due to the caloric contribution of glucose or to some other effect. Glucose sensed by the cells activates signaling pathways that, in yeast, favor the metabolic machinery that makes energy (glycolysis) and cell growth. The sensing of glucose also reduces stress resistance and the ability to live long. Does glucose provoke a pro-aging effect as a result of its metabolic activity or by activating signaling pathways? Here we addressed this question by studying the role of a glucose-signaling pathway in the life span of the fission yeast S. pombe. Genetic inactivation of the glucose-signaling pathway prolonged life span in this yeast, while its constitutive activation shortened it and blocked the longevity effects of calorie restriction. The pro-aging effects of glucose signaling correlated with a decrease in mitochondrial respiration and an increase in reactive oxygen species production. Moreover, a strain without glucose metabolism is still sensitive to detrimental effects of glucose due to signaling. Our work shows that glucose signaling through the glucose receptor GIT3 constitutes the main cause responsible for the pro-aging effects of glucose in fission yeast.
登录
查看更多内容
影响因子：
10.5
作者：
HOFFMAN, CS;WINSTON, F
通讯作者：
WINSTON, F
影响因子：
5.3
作者：
Higuchi, T;Watanabe, Y;Yamamoto, M
通讯作者：
Yamamoto, M
影响因子：
4.3
作者：
Bonini, BM;Van Dijck, P;Thevelein, JM
通讯作者：
Thevelein, JM
DOI：
10.1099/13500872-142-6-1399
发表时间：
1996-06-01
期刊：
MICROBIOLOGY-UK
影响因子：
--
作者：
deJongGubbels, P;vanDijken, JP;Pronk, JT
通讯作者：
Pronk, JT
影响因子：
4.4
作者：
Jansen, MLA;De Winde, JH;Pronk, JT
通讯作者：
Pronk, JT