Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.

Rapamycin was found to increase (11% to 16%) the lifespan of male and female C57BL/6J mice most likely by reducing the increase in the hazard for mortality (i.e., the rate of aging) term in the Gompertz mortality analysis. To identify the pathways that could be responsible for rapamycin's longe...

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Main Authors: Wilson C Fok, Yidong Chen, Alex Bokov, Yiqiang Zhang, Adam B Salmon, Vivian Diaz, Martin Javors, William H Wood, Yongqing Zhang, Kevin G Becker, Viviana I Pérez, Arlan Richardson
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3883653?pdf=render
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author Wilson C Fok
Yidong Chen
Alex Bokov
Yiqiang Zhang
Adam B Salmon
Vivian Diaz
Martin Javors
William H Wood
Yongqing Zhang
Kevin G Becker
Viviana I Pérez
Arlan Richardson
author_facet Wilson C Fok
Yidong Chen
Alex Bokov
Yiqiang Zhang
Adam B Salmon
Vivian Diaz
Martin Javors
William H Wood
Yongqing Zhang
Kevin G Becker
Viviana I Pérez
Arlan Richardson
author_sort Wilson C Fok
collection DOAJ
description Rapamycin was found to increase (11% to 16%) the lifespan of male and female C57BL/6J mice most likely by reducing the increase in the hazard for mortality (i.e., the rate of aging) term in the Gompertz mortality analysis. To identify the pathways that could be responsible for rapamycin's longevity effect, we analyzed the transcriptome of liver from 25-month-old male and female mice fed rapamycin starting at 4 months of age. Few changes (<300 transcripts) were observed in transcriptome of rapamycin-fed males; however, a large number of transcripts (>4,500) changed significantly in females. Using multidimensional scaling and heatmap analyses, the male mice fed rapamycin were found to segregate into two groups: one group that is almost identical to control males (Rapa-1) and a second group (Rapa-2) that shows a change in gene expression (>4,000 transcripts) with more than 60% of the genes shared with female mice fed Rapa. Using ingenuity pathway analysis, 13 pathways were significantly altered in both Rapa-2 males and rapamycin-fed females with mitochondrial function as the most significantly changed pathway. Our findings show that rapamycin has a major effect on the transcriptome and point to several pathways that would likely impact the longevity.
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spelling doaj.art-b87bcfcb78e646c3b77649ae5180f55d2022-12-21T19:00:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8398810.1371/journal.pone.0083988Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.Wilson C FokYidong ChenAlex BokovYiqiang ZhangAdam B SalmonVivian DiazMartin JavorsWilliam H WoodYongqing ZhangKevin G BeckerViviana I PérezArlan RichardsonRapamycin was found to increase (11% to 16%) the lifespan of male and female C57BL/6J mice most likely by reducing the increase in the hazard for mortality (i.e., the rate of aging) term in the Gompertz mortality analysis. To identify the pathways that could be responsible for rapamycin's longevity effect, we analyzed the transcriptome of liver from 25-month-old male and female mice fed rapamycin starting at 4 months of age. Few changes (<300 transcripts) were observed in transcriptome of rapamycin-fed males; however, a large number of transcripts (>4,500) changed significantly in females. Using multidimensional scaling and heatmap analyses, the male mice fed rapamycin were found to segregate into two groups: one group that is almost identical to control males (Rapa-1) and a second group (Rapa-2) that shows a change in gene expression (>4,000 transcripts) with more than 60% of the genes shared with female mice fed Rapa. Using ingenuity pathway analysis, 13 pathways were significantly altered in both Rapa-2 males and rapamycin-fed females with mitochondrial function as the most significantly changed pathway. Our findings show that rapamycin has a major effect on the transcriptome and point to several pathways that would likely impact the longevity.http://europepmc.org/articles/PMC3883653?pdf=render
spellingShingle Wilson C Fok
Yidong Chen
Alex Bokov
Yiqiang Zhang
Adam B Salmon
Vivian Diaz
Martin Javors
William H Wood
Yongqing Zhang
Kevin G Becker
Viviana I Pérez
Arlan Richardson
Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.
PLoS ONE
title Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.
title_full Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.
title_fullStr Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.
title_full_unstemmed Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.
title_short Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.
title_sort mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome
url http://europepmc.org/articles/PMC3883653?pdf=render
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