Date of Award

2017

Degree Type

Thesis

Degree Name

Master of Science in Biology

Department

Biology

First Advisor

Kondratov, Roman

Subject Headings

Biology, Molecular Biology

Abstract

The rhythms in the expression of circadian clock genes are affected by calorie restriction (CR), a dietary paradigm known to increase lifespan. In our current study, we show that circadian rhythms are influenced by sex and the effects of CR are different between males and females. In particular, we found a group of clock genes which showed a sex-dependent difference in expression, as well as in response to CR (Rev-Erb α, Ror γ and both Cryptochromes: Cry1 and Cry2 genes). Two clock genes showed no difference in expression but their response to CR showed sexual dimorphism (Ror α and Rev-Erb β). Finally, we found some of the clock genes to be expressed in a sex-independent manner (Bmal1, Per1, Per2 and Per3). The response to CR for these genes did not show sexual dimorphism as well. Several genes were also previously reported to be regulated by CR. These genes showed a sex-dependent difference in expression as well as the sexual dimorphism in the response to CR in mouse liver (Fmo3, Mup4, Serpina12, Cyp4a12b and Cyp4a14a). IGF signaling plays an important role in aging and CR effects. Igf-1 expression is regulated by CR and by the circadian clock, we found that rhythms in Igf-1 expression have sexual dimorphism.

We also investigated the differences in expression levels in young versus old mice to see if the effect of short-term CR differs from the effect of long-term CR. In all of the 4 analyzed genes, the expression does not change with age. The effect of CR on the expression of 2 out of 4 genes (Bmal1 and Per2) was lost upon long-term exposure to CR. For the other 2 genes (Per1 and Per3) the effect of CR persisted over time. Thus we emphasize that sex and age are important factors for consideration when administering CR.

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