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Gene expression in the liver of female, but not male mice treated with rapamycin resembles changes observed under dietary restriction

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https://ir.library.oregonstate.edu/concern/articles/2f75r9575

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  • It is well known that in mice the extension in lifespan by rapamycin is sexually dimorphic, in that it has a larger effect in females than males. In a previous study we showed that in male C57BL6 mice, rapamycin had less profound effects in both gene expression and liver metabolites when compared to dietary restriction (DR), but no data was available in females. Because recent studies showed that rapamycin increases longevity in a dose dependent manner and at every dose tested the effect remains larger in females than in males, we hypothesized that rapamycin should have a stronger effect on gene expression in females, and this effect could be dose dependent. To test this hypothesis, we measured the changes in liver gene expression induced by rapamycin (14 ppm) with a focus on several genes involved in pathways known to play a role in aging and that are altered by DR. To investigate whether any effects are dose dependent, we also analyzed females treated with two additional doses of rapamycin (22 and 42 ppm). We observed striking differences between male and female in gene expression at 14 ppm, where females have a larger response to rapamycin than males, and the effects of rapamycin in females resemble what we observed under DR. However, these effects were generally not dose dependent. These data support the notion that female mice respond better to rapamycin, and at least with the set of genes studied here, the effect of rapamycin in females resemble the effect of DR.
  • This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Springer. The published article can be found at: http://www.springerplus.com/
  • Keywords: Female mice, Gene expression, Dietary restriction, Rapamycin, Longevity pathways
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  • Yu, Z., Sunchu, B., Fok, W. C., Alshaikh, N., & Pérez, V. I. (2015). Gene expression in the liver of female, but not male mice treated with rapamycin resembles changes observed under dietary restriction. SpringerPlus, 4, 174. doi:10.1186/s40064-015-0909-7
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  • 4
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  • Financial support was provided by National Institutional of Health (NIH) RC2 Grand Opportunity grant (AG036613, Arlan Richardson PI), The San Antonio Nathan Shock Aging Center (1P30-AG-13319, AR), NIH T32 Training Grant (AG021890, WF), The Ellison Medical Foundation (VIP), and start-up funds from the Dept. of Biochemistry and Biophysics and The Linus Pauling Institute (VP).
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