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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Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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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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institution | Directory Open Access Journal |
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language | English |
last_indexed | 2024-12-21T14:43:39Z |
publishDate | 2014-01-01 |
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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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