Ruan Hongyu, Tang Xiang Dong, Chen Mai-Lei, Joiner Mei-Ling A, Sun Guangrong, Brot Nathan, Weissbach Herbert, Heinemann Stefan H, Iverson Linda, Wu Chun-Fang, Hoshi Toshinori
Department of Biological Sciences, University of Iowa, Iowa City, IA 52242, USA.
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2748-53. doi: 10.1073/pnas.032671199. Epub 2002 Feb 26.
Cumulative oxidative damages to cell constituents are considered to contribute to aging and age-related diseases. The enzyme peptide methionine sulfoxide reductase A (MSRA) catalyzes the repair of oxidized methionine in proteins by reducing methionine sulfoxide back to methionine. However, whether MSRA plays a role in the aging process is poorly understood. Here we report that overexpression of the msrA gene predominantly in the nervous system markedly extends the lifespan of the fruit fly Drosophila. The MSRA transgenic animals are more resistant to paraquat-induced oxidative stress, and the onset of senescence-induced decline in the general activity level and reproductive capacity is delayed markedly. The results suggest that oxidative damage is an important determinant of lifespan, and MSRA may be important in increasing the lifespan in other organisms including humans.
细胞成分的累积氧化损伤被认为与衰老及与年龄相关的疾病有关。酶肽甲硫氨酸亚砜还原酶A（MSRA）通过将甲硫氨酸亚砜还原回甲硫氨酸来催化修复蛋白质中氧化的甲硫氨酸。然而，MSRA是否在衰老过程中发挥作用却知之甚少。在此我们报告，msrA基因主要在神经系统中的过表达显著延长了果蝇的寿命。MSRA转基因动物对百草枯诱导的氧化应激更具抗性，并且衰老诱导的一般活动水平和生殖能力下降的起始被显著延迟。这些结果表明氧化损伤是寿命的一个重要决定因素，并且MSRA在延长包括人类在内的其他生物体的寿命方面可能很重要。
