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Short-Term Treatment With Rapamycin and Dietary Restriction Have Overlapping and Distinctive Effects in Young Mice

Because rapamycin, an inhibitor of the nutrient sensor mammalian target of rapamycin, and dietary restriction both increase life span of mice, it has been hypothesized that they act through similar mechanisms. To test this hypothesis, we compared various biological parameters in dietary restriction...

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Autores principales: Fok, Wilson C., Zhang, Yiqiang, Salmon, Adam B., Bhattacharya, Arunabh, Gunda, Rakesh, Jones, Dean, Ward, Walter, Fisher, Kathleen, Richardson, Arlan, Pérez, Viviana I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598360/
https://www.ncbi.nlm.nih.gov/pubmed/22570137
http://dx.doi.org/10.1093/gerona/gls127
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author Fok, Wilson C.
Zhang, Yiqiang
Salmon, Adam B.
Bhattacharya, Arunabh
Gunda, Rakesh
Jones, Dean
Ward, Walter
Fisher, Kathleen
Richardson, Arlan
Pérez, Viviana I.
author_facet Fok, Wilson C.
Zhang, Yiqiang
Salmon, Adam B.
Bhattacharya, Arunabh
Gunda, Rakesh
Jones, Dean
Ward, Walter
Fisher, Kathleen
Richardson, Arlan
Pérez, Viviana I.
author_sort Fok, Wilson C.
collection PubMed
description Because rapamycin, an inhibitor of the nutrient sensor mammalian target of rapamycin, and dietary restriction both increase life span of mice, it has been hypothesized that they act through similar mechanisms. To test this hypothesis, we compared various biological parameters in dietary restriction mice (40% food restriction) and mice fed rapamycin (14 ppm). Both treatments led to a significant reduction in mammalian target of rapamycin signaling and a corresponding increase in autophagy. However, we observed striking differences in fat mass, insulin sensitivity, and expression of cell cycle and sirtuin genes in mice fed rapamycin compared with dietary restriction. Thus, although both treatments lead to significant downregulation of mammalian target of rapamycin signaling, these two manipulations have quite different effects on other physiological functions suggesting that they might increase life span through a common pathway as well as pathways that are altered differently by dietary restriction and rapamycin.
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spelling pubmed-35983602013-03-15 Short-Term Treatment With Rapamycin and Dietary Restriction Have Overlapping and Distinctive Effects in Young Mice Fok, Wilson C. Zhang, Yiqiang Salmon, Adam B. Bhattacharya, Arunabh Gunda, Rakesh Jones, Dean Ward, Walter Fisher, Kathleen Richardson, Arlan Pérez, Viviana I. J Gerontol A Biol Sci Med Sci Original Article Because rapamycin, an inhibitor of the nutrient sensor mammalian target of rapamycin, and dietary restriction both increase life span of mice, it has been hypothesized that they act through similar mechanisms. To test this hypothesis, we compared various biological parameters in dietary restriction mice (40% food restriction) and mice fed rapamycin (14 ppm). Both treatments led to a significant reduction in mammalian target of rapamycin signaling and a corresponding increase in autophagy. However, we observed striking differences in fat mass, insulin sensitivity, and expression of cell cycle and sirtuin genes in mice fed rapamycin compared with dietary restriction. Thus, although both treatments lead to significant downregulation of mammalian target of rapamycin signaling, these two manipulations have quite different effects on other physiological functions suggesting that they might increase life span through a common pathway as well as pathways that are altered differently by dietary restriction and rapamycin. Oxford University Press 2013-02 2012-05-08 /pmc/articles/PMC3598360/ /pubmed/22570137 http://dx.doi.org/10.1093/gerona/gls127 Text en © The Author 2012. Published by Oxford University Press on behalf of The Gerontological Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Fok, Wilson C.
Zhang, Yiqiang
Salmon, Adam B.
Bhattacharya, Arunabh
Gunda, Rakesh
Jones, Dean
Ward, Walter
Fisher, Kathleen
Richardson, Arlan
Pérez, Viviana I.
Short-Term Treatment With Rapamycin and Dietary Restriction Have Overlapping and Distinctive Effects in Young Mice
title Short-Term Treatment With Rapamycin and Dietary Restriction Have Overlapping and Distinctive Effects in Young Mice
title_full Short-Term Treatment With Rapamycin and Dietary Restriction Have Overlapping and Distinctive Effects in Young Mice
title_fullStr Short-Term Treatment With Rapamycin and Dietary Restriction Have Overlapping and Distinctive Effects in Young Mice
title_full_unstemmed Short-Term Treatment With Rapamycin and Dietary Restriction Have Overlapping and Distinctive Effects in Young Mice
title_short Short-Term Treatment With Rapamycin and Dietary Restriction Have Overlapping and Distinctive Effects in Young Mice
title_sort short-term treatment with rapamycin and dietary restriction have overlapping and distinctive effects in young mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598360/
https://www.ncbi.nlm.nih.gov/pubmed/22570137
http://dx.doi.org/10.1093/gerona/gls127
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