TitleMice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.
Publication TypeJournal Article
Year of Publication2014
AuthorsFok WC, Chen Y, Bokov A, Zhang Y, Salmon AB, Diaz V, Javors M, Wood WH, Zhang Y, Becker KG, Perez VI, Richardson A
JournalPLoS One
Date Published2014
KeywordsAnimals, Cluster Analysis, Diet, Female, Gene Expression Profiling, Gene Expression Regulation, Liver, Longevity, Male, Mice, Sex Factors, Signal Transduction, Sirolimus, 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 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.

Alternate JournalPLoS ONE
PubMed ID24409289
PubMed Central IDPMC3883653
Grant ListG12MD007591 / MD / NIMHD NIH HHS / United States
T32 AG021890 / AG / NIA NIH HHS / United States
G12 MD007591 / MD / NIMHD NIH HHS / United States
/ / Intramural NIH HHS / United States
RC2 AG036613 / AG / NIA NIH HHS / United States