Neuronal expression of p53 dominant-negative proteins in adult Drosophila melanogaster extends life span
Neuronal expression of p53 dominant-negative proteins in adult Drosophila melanogaster extends life span
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DOI：
10.1016/j.cub.2005.10.051
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发表时间：
2005-11-22
期刊：
影响因子：
9.2
通讯作者：
Helfand, SL
中科院分区：
文献类型：
--
作者：
Bauer, JH;Poon, PC;Helfand, SL
在两种不同的模型系统中，p53的超活化导致肿瘤形成减少和寿命意外缩短[1，2]。寿命缩短伴随着加速老化的迹象，如骨质疏松症、体重减轻、器官萎缩、抗应激能力下降和造血干细胞耗竭。这些观察结果表明p53在寿命的决定中的作用，并推测降低p53活性可能对某些衰老表型产生积极影响[3，4]。在这份报告中，我们表明，表达显性阴性版本的果蝇p53在成年神经元延长寿命，增加遗传毒性应激抗性的苍蝇。与此相一致，具有降低的p53活性的天然存在的等位基因与人类的延长生存期相关[5]。显性负性果蝇p53结构的表达并没有进一步增加被热量限制的果蝇的寿命延长，这表明p53活性的降低可能介导果蝇中热量限制寿命延长途径的一个组成部分。
Hyperactivation of p53 leads to a reduction in tumor formation and an unexpected shortening of life span in two different model systems [1, 2]. The decreased life span occurs with signs of accelerated aging, such as osteoporosis, reduction in body weight, atrophy of organs, decreased stress resistance, and depletion of hematopoietic stem cells. These observations suggest a role for p53 in the determination of life span and the speculation that decreasing p53 activity may result in positive effects on some aging phenotypes [3, 4]. In this report, we show that expression of dominant-negative versions of Drosophila melanogaster p53 in adult neurons extends life span and increases genotoxic stress resistance in the fly. Consistent with this, a naturally occurring allele with decreased p53 activity has been associated with extended survival in humans [5]. Expression of the dominant-negative Drosophila melanogaster p53 constructs does not further increase the extended life span of flies that are calorie restricted, suggesting that a decrease in p53 activity may mediate a component of the calorie-restriction life span-extending pathway in flies.