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

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 del...

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Autores principales: Komarova, Elena A., Antoch, Marina P., Novototskaya, Liliya R., Chernova, Olga B., Paszkiewicz, Geraldine, Leontieva, Olga V., Blagosklonny, Mikhail V., Gudkov, Andrei V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2012
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517941/
https://www.ncbi.nlm.nih.gov/pubmed/23123616
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author Komarova, Elena A.
Antoch, Marina P.
Novototskaya, Liliya R.
Chernova, Olga B.
Paszkiewicz, Geraldine
Leontieva, Olga V.
Blagosklonny, Mikhail V.
Gudkov, Andrei V.
author_facet Komarova, Elena A.
Antoch, Marina P.
Novototskaya, Liliya R.
Chernova, Olga B.
Paszkiewicz, Geraldine
Leontieva, Olga V.
Blagosklonny, Mikhail V.
Gudkov, Andrei V.
author_sort Komarova, Elena A.
collection PubMed
description 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.
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spelling pubmed-35179412012-12-10 Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/− mice Komarova, Elena A. Antoch, Marina P. Novototskaya, Liliya R. Chernova, Olga B. Paszkiewicz, Geraldine Leontieva, Olga V. Blagosklonny, Mikhail V. Gudkov, Andrei V. Aging (Albany NY) Research Paper 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. Impact Journals LLC 2012-10-29 /pmc/articles/PMC3517941/ /pubmed/23123616 Text en Copyright: © 2012 Komarova et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
spellingShingle Research Paper
Komarova, Elena A.
Antoch, Marina P.
Novototskaya, Liliya R.
Chernova, Olga B.
Paszkiewicz, Geraldine
Leontieva, Olga V.
Blagosklonny, Mikhail V.
Gudkov, Andrei V.
Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/− mice
title Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/− mice
title_full Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/− mice
title_fullStr Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/− mice
title_full_unstemmed Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/− mice
title_short Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/− mice
title_sort rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/− mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517941/
https://www.ncbi.nlm.nih.gov/pubmed/23123616
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