Abstract
The rhythms in the expression of circadian clock genes are affected by calorie restriction (CR), a dietary paradigm known to increase lifespan. Many physiological effects of CR differ between males and females; here we investigated if the sex of animals affects the CR induced changes in the circadian rhythms. The liver expression of some circadian clock genes such as Bmal1 and three Periods (Per1, Per2 and Per3) and the effect of CR on the expression of these genes were sex independent, while the expression of Rev-Erb alpha, Ror gamma and both Cryptochome (Cry1 and Cry2) genes was different between males and females. The effect of CR on Rev-Erb alpha, Ror gamma and Cry1 gene expression was sex dependent. The expression and the effects of CR were sex-specific for several genes previously reported to be regulated by CR: Fmo3, Mup4, Serpina12 and Cyp4a12, while the expression of Cyp4a14a was sex independent. 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. Our data provide molecular evidence that the sex of animals is an important modulator of circadian rhythms in gene expression and their response to CR.
Highlights
The increase in lifespan and delay of aging by caloric restriction (CR) is well documented in many organisms, including mammals[1]
In the previous study we found that the daily rhythms in the expression of Bmal[1], Per[1], Per[2], Per[3], Cry[2] and Ror γ were significantly affected by calorie restriction (CR) in the liver of male mice[8]
While at some time points (ZT2 for Bmal[1], ZT10 for Per[1] and Per3) we observed a statistically significant difference between the expressions in males and females on CR, the changes in the expression were still observed for both males and females and these changes were towards the same direction
Summary
The increase in lifespan and delay of aging by caloric restriction (CR) is well documented in many organisms, including mammals[1]. CR affects many physiological systems - it causes changes in the levels of many hormones, improves glucose homeostasis, mitochondrial functioning and proteostasis, increases resistance to stress and reduces incidence of cancer[2]. All these changes are considered beneficial for health and longevity. Us and other researchers reported that CR affects the daily rhythms in the expression of several circadian clock genes in mammals and flies and proposed that circadian clocks might be involved in CR mechanisms[7, 8]. In the present report we compared the effect of CR on circadian rhythms in gene expression between male and female mice
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