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

  • Elena A. Komarova
  • , Marina P. Antoch
  • , Liliya R. Novototskaya
  • , Olga B. Chernova
  • , Geraldine Paszkiewicz
  • , Olga V. Leontieva
  • , Mikhail V. Blagosklonny
  • , Andrei V. Gudkov
  • Roswell Park Cancer Institute
  • OncoTartis, Inc.

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

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.

Original languageEnglish
Pages (from-to)709-714
Number of pages6
JournalAging
Volume4
Issue number10
DOIs
StatePublished - 2012

Keywords

  • Aging
  • cancer
  • Dna damage
  • Mtor
  • Mutations

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