Characterization of Per2 and SIRT1 : age-related tissue distribution changes

Abstract

The circadian clock supports and governs many body physiological processes. Period2 (PER2) is a key molecule regulating the circadian clock and acts as a repressor clock protein in the transcriptional-translational feedback loops. SIRT1 (a member of the sirtuin family) is a class III histone deacetylase regulating metabolism, genome stability and ageing. The present study investigated the tissue distribution and agerelated changes in SIRT1 expression. This protein was expressed differentially across various organs with high expression levels in those with high metabolic rate – kidney, heart, liver, and brain. During physiological ageing, SIRT1 expression declined at both transcriptional and translational levels.

The present study also examined the crosstalks between Per2 and SIRT1 especially in the brain, heart, aorta, extensor digitalis longus (EDL) and soleus muscle. In Per2 mutant mice, SIRT1 expression was upregulated in heart, aorta, EDL and soleus but downregulated in the brain. Overexpression of human SIRT1 in endothelial cells repressed Per2 transcription in heart, aorta, EDL and soleus; and elevated Per2 expression in the brain. Interestingly, SIRT1 activity decreased in Per2 mutant mice despite of increased SIRT1 expressions. The results indicated that post-translational modification of SIRT1 affected its protein activity. The study collectively demonstrated that a reciprocal relationship between SIRT1 and Per2 in brain as well as peripheral organs, such as heart, aorta, and skeletal muscles.