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Mice Fed Rapamycin Have an Increase in Lifespan Associated with Major Changes in the Liver Transcriptome

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Title Mice Fed Rapamycin Have an Increase in Lifespan Associated with Major Changes in the Liver Transcriptome
Names Fok, Wilson C. (creator)
Chen, Yidong (creator)
Bokov, Alex (creator)
Zhang, Yiqiang (creator)
Salmon, Adam B. (creator)
Diaz, Vivian (creator)
Javors, Martin (creator)
Wood, William H., III (creator)
Zhang, Yongqing (creator)
Becker, Kevin G. (creator)
Pérez, Viviana I. (creator)
Richardson, Arlan (creator)
Date Issued 2014-01-07 (iso8601)
Note This is the publisher’s final pdf. The article was published by the Public Library of Science and is in the public domain. The published article can be found at: http://www.plosone.org/.
Abstract 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.
Genre Article
Access Condition http://creativecommons.org/publicdomain/zero/1.0/
Identifier Fok WC, Chen Y, Bokov A, Zhang Y, Salmon AB, et al. (2014) Mice Fed Rapamycin Have an Increase in Lifespan Associated with Major Changes in the Liver Transcriptome. PLoS ONE 9(1): e83988. doi:10.1371/journal.pone.0083988

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