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Research Paper|Volume 4, Issue 10|pp 709—714

Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/− mice

Elena A. Komarova1, Marina P. Antoch2, Liliya R. Novototskaya1, Olga B. Chernova3, Geraldine Paszkiewicz1, Olga V. Leontieva1, Mikhail V. Blagosklonny1, Andrei V. Gudkov1
  • 1Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC, L3-312, Buffalo, NY 14263, USA
  • 2Department of Molecular & Cellular Biology, Roswell Park Cancer Institute, BLSC, L3-312, Buffalo, NY 14263, USA
  • 3Tartis Aging, Inc., Buffalo, NY 14203, USA
Received: August 30, 2012Accepted: October 27, 2012Published: October 29, 2012

Abstract

The 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.