Digging in to the Epigenetics of Rapamycin-Induced Longevity

There is some debate over whether rapamycin extends life in mice by actually slowing aging or by merely reducing cancer risk. There will be more studies like this one in which researchers gather a great deal of data about the effects of rapamycin on epigenetic profiles and other detailed aspects of mouse biology:

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 ( less than 300 transcripts) were observed in transcriptome of rapamycin-fed males; however, a large number of transcripts (more than 4,500) changed significantly in females.

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 (more than 4,000 transcripts) with more than 60% of the genes shared with female mice fed Rapa. 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 longevity.

Link: http://dx.doi.org/10.1371/journal.pone.0083988

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