MnSOD overexpression extends the yeast chronological (G0) life span but acts independently of Sir2p histone deacetylase to shorten the replicative life span of dividing cells
MnSOD overexpression extends the yeast chronological (G0) life span but acts independently of Sir2p histone deacetylase to shorten the replicative life span of dividing cells
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DOI：
10.1016/s0891-5849(03)00210-7
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发表时间：
2003-06-15
影响因子：
7.4
通讯作者：
Piper, PW
中科院分区：
文献类型：
--
作者：
Harris, N;Costa, V;Piper, PW
对果蝇和秀丽隐杆线虫的研究表明，随着氧化剂清除酶的过度表达，自由基清除能力增加，寿命延长。这项研究使用酵母，另一种衰老研究模型，来探讨过表达线粒体呼吸链产生的主要活性保护超氧化物的影响。锰超氧化物歧化酶（MnSOD）过表达增加了时间寿命（随着时间的推移，静止（G（0））酵母的最佳存活），表明这是一种最终受氧化应激限制的存活。相比之下，同样的过度表达大大减少了分裂细胞的复制寿命（每个新生母细胞产生的子芽的数量）。MnSOD过表达的世代寿命的这种减少大于酵母复制寿命的主要氧化还原反应调节剂NAD+依赖性Sir2p组蛋白脱乙酰酶的损失所产生的。它也独立于后者的活动。在MnSOD过表达子中表达一种靶向细胞的绿色荧光蛋白，表明该过表达子的老母细胞分裂了几代，在从母细胞到子细胞的分离中存在缺陷。因此，线粒体缺陷是MnSOD过表达缩短复制寿命的可能原因。(C)2003年爱思唯尔公司
Studies in Drosophila and Caenorhabditis elegans have shown increased longevity with the increased free radical scavenging that accompanies overexpression of oxidant-scavenging enzymes. This study used yeast, another model for aging research, to probe the effects of overexpressing the major activity protecting against superoxide generated by the mitochondrial respiratory chain. Manganese superoxide dismutase (MnSOD) overexpression increased chronological life span (optimized survival of stationary (G(0)) yeast over time), showing this is a survival ultimately limited by oxidative stress. In contrast, the same overexpression dramatically reduced the replicative life span of dividing cells (the number of daughter buds produced by each newly born mother cell). This reduction in the generational life span by MnSOD overexpression was greater than that generated by loss of the major redox-responsive regulator of the yeast replicative life span, NAD+-dependent Sir2p histone deacetylase. It was also independent of the latter activity. Expression of a mitochondrially targeted green fluorescent protein in the MnSOD overexpressor revealed that the old mother cells of this overexpressor, which had divided for a few generations, were defective in segregation of the mitochondrion from the mother to daughter. Mitochondrial defects are, therefore, the probable reason that MnSOD overexpression shortens replicative life span. (C) 2003 Elsevier Inc.