Waskar Morris, Landis Gary N, Shen Jie, Curtis Christina, Tozer Kevin, Abdueva Diana, Skvortsov Dmitriy, Tavaré Simon, Tower John
Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2910, USA.
Aging (Albany NY). 2009 Oct 27;1(11):903-36. doi: 10.18632/aging.100099.
Truncated and mutant forms ofp53 affect life span in Drosophila, nematodes and mice, however the role of wild-type p53 in aging remains unclear. Here conditional over-expression of both wild-type and mutant p53 transgenes indicated that, in adult flies, p53 limits life span in females but favors life span in males. In contrast, during larval development, moderate over-expression of p53 produced both male and female adults with increased life span. Mutations of the endogenous p53 gene also had sex-specific effects on life span under control and stress conditions: null mutation of p53 increased life span in females, and had smaller, more variable effects in males. These developmental stage-specific and sex-specific effects of p53 on adult life span are consistent with a sexual antagonistic pleiotropy model.
截短型和突变型p53会影响果蝇、线虫和小鼠的寿命，然而野生型p53在衰老过程中的作用仍不清楚。在此，野生型和突变型p53转基因的条件性过表达表明，在成年果蝇中，p53限制雌性寿命，但有利于雄性寿命。相反，在幼虫发育期间，p53的适度过表达产生了寿命延长的雌雄成虫。内源性p53基因的突变在对照和应激条件下对寿命也有性别特异性影响：p53基因敲除增加了雌性的寿命，而对雄性的影响较小且更具变异性。p53对成年寿命的这些发育阶段特异性和性别特异性影响与性拮抗多效性模型一致。
