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Gene expression in the liver of female, but not male mice treated with rapamycin resembles changes observed under dietary restriction

It is well known that in mice the extension in lifespan by rapamycin is sexually dimorphic, in that it has a larger effect in females than males. In a previous study we showed that in male C57BL6 mice, rapamycin had less profound effects in both gene expression and liver metabolites when compared to...

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Autores principales: Yu, Zhen, Sunchu, Bharath, Fok, Wilson C, Alshaikh, Nahla, Pérez, Viviana I
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447730/
https://www.ncbi.nlm.nih.gov/pubmed/26034704
http://dx.doi.org/10.1186/s40064-015-0909-7
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author Yu, Zhen
Sunchu, Bharath
Fok, Wilson C
Alshaikh, Nahla
Pérez, Viviana I
author_facet Yu, Zhen
Sunchu, Bharath
Fok, Wilson C
Alshaikh, Nahla
Pérez, Viviana I
author_sort Yu, Zhen
collection PubMed
description It is well known that in mice the extension in lifespan by rapamycin is sexually dimorphic, in that it has a larger effect in females than males. In a previous study we showed that in male C57BL6 mice, rapamycin had less profound effects in both gene expression and liver metabolites when compared to dietary restriction (DR), but no data was available in females. Because recent studies showed that rapamycin increases longevity in a dose dependent manner and at every dose tested the effect remains larger in females than in males, we hypothesized that rapamycin should have a stronger effect on gene expression in females, and this effect could be dose dependent. To test this hypothesis, we measured the changes in liver gene expression induced by rapamycin (14 ppm) with a focus on several genes involved in pathways known to play a role in aging and that are altered by DR. To investigate whether any effects are dose dependent, we also analyzed females treated with two additional doses of rapamycin (22 and 42 ppm). We observed striking differences between male and female in gene expression at 14 ppm, where females have a larger response to rapamycin than males, and the effects of rapamycin in females resemble what we observed under DR. However, these effects were generally not dose dependent. These data support the notion that female mice respond better to rapamycin, and at least with the set of genes studied here, the effect of rapamycin in females resemble the effect of DR. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-0909-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-44477302015-06-01 Gene expression in the liver of female, but not male mice treated with rapamycin resembles changes observed under dietary restriction Yu, Zhen Sunchu, Bharath Fok, Wilson C Alshaikh, Nahla Pérez, Viviana I Springerplus Research It is well known that in mice the extension in lifespan by rapamycin is sexually dimorphic, in that it has a larger effect in females than males. In a previous study we showed that in male C57BL6 mice, rapamycin had less profound effects in both gene expression and liver metabolites when compared to dietary restriction (DR), but no data was available in females. Because recent studies showed that rapamycin increases longevity in a dose dependent manner and at every dose tested the effect remains larger in females than in males, we hypothesized that rapamycin should have a stronger effect on gene expression in females, and this effect could be dose dependent. To test this hypothesis, we measured the changes in liver gene expression induced by rapamycin (14 ppm) with a focus on several genes involved in pathways known to play a role in aging and that are altered by DR. To investigate whether any effects are dose dependent, we also analyzed females treated with two additional doses of rapamycin (22 and 42 ppm). We observed striking differences between male and female in gene expression at 14 ppm, where females have a larger response to rapamycin than males, and the effects of rapamycin in females resemble what we observed under DR. However, these effects were generally not dose dependent. These data support the notion that female mice respond better to rapamycin, and at least with the set of genes studied here, the effect of rapamycin in females resemble the effect of DR. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-0909-7) contains supplementary material, which is available to authorized users. Springer International Publishing 2015-04-11 /pmc/articles/PMC4447730/ /pubmed/26034704 http://dx.doi.org/10.1186/s40064-015-0909-7 Text en © Yu et al.; licensee Springer. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Research
Yu, Zhen
Sunchu, Bharath
Fok, Wilson C
Alshaikh, Nahla
Pérez, Viviana I
Gene expression in the liver of female, but not male mice treated with rapamycin resembles changes observed under dietary restriction
title Gene expression in the liver of female, but not male mice treated with rapamycin resembles changes observed under dietary restriction
title_full Gene expression in the liver of female, but not male mice treated with rapamycin resembles changes observed under dietary restriction
title_fullStr Gene expression in the liver of female, but not male mice treated with rapamycin resembles changes observed under dietary restriction
title_full_unstemmed Gene expression in the liver of female, but not male mice treated with rapamycin resembles changes observed under dietary restriction
title_short Gene expression in the liver of female, but not male mice treated with rapamycin resembles changes observed under dietary restriction
title_sort gene expression in the liver of female, but not male mice treated with rapamycin resembles changes observed under dietary restriction
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447730/
https://www.ncbi.nlm.nih.gov/pubmed/26034704
http://dx.doi.org/10.1186/s40064-015-0909-7
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