Komarova Elena A, Antoch Marina P, Novototskaya Liliya R, Chernova Olga B, Paszkiewicz Geraldine, Leontieva Olga V, Blagosklonny Mikhail V, Gudkov Andrei V
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Aging (Albany NY). 2012 Oct;4(10):709-14. doi: 10.18632/aging.100498.
TOR (Target of Rapamycin) pathway accelerates cellular and organismal aging. Similar to rapamycin, p53 can inhibit the mTOR pathway in some mammalian cells. Mice lacking one copy of p53 (p53+/- mice) have an increased cancer incidence and a shorter lifespan. We hypothesize that rapamycin can delay cancer in heterozygous p53+/- mice. Here we show that rapamycin (given in a drinking water) extended the mean lifespan of p53+/- mice by 10% and when treatment started early in life (at the age less than 5 months) by 28%. In addition, rapamycin decreased the incidence of spontaneous tumors. This observation may have applications in management of Li-Fraumeni syndrome patients characterized by heterozygous mutations in the p53 gene.
雷帕霉素靶蛋白(TOR)信号通路会加速细胞和机体衰老。与雷帕霉素类似,p53在某些哺乳动物细胞中可抑制mTOR信号通路。缺失一个p53拷贝的小鼠(p53+/-小鼠)癌症发病率增加且寿命缩短。我们推测雷帕霉素可延缓杂合p53+/-小鼠患癌。在此我们表明,雷帕霉素(通过饮用水给予)使p53+/-小鼠的平均寿命延长了10%,若在生命早期(小于5个月龄)开始治疗则延长了28%。此外,雷帕霉素降低了自发肿瘤的发生率。这一观察结果可能对以p53基因杂合突变为特征的李-佛美尼综合征患者的治疗有应用价值。