title: Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/- mice.
abstract: 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.
authors.affiliation: Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Komarova
authors.forename: Marina P
authors.initials: MP
authors.lastname: Antoch
authors.forename: Liliya R
authors.initials: LR
authors.lastname: Novototskaya
authors.forename: Olga B
authors.initials: OB
authors.lastname: Chernova
authors.forename: Geraldine
authors.initials: G
authors.lastname: Paszkiewicz
authors.forename: Olga V
authors.initials: OV
authors.lastname: Leontieva
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Blagosklonny
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Gudkov
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D005260:Female; D016158:Genes, p53; D016864:Li-Fraumeni Syndrome / Q000188:drug therapy; D008136:Longevity / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020123:Sirolimus / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000903:Antibiotics, Antineoplastic; D020123:Sirolimus