Age-Related Changes in Sirtuin 7 Expression in Calorie-Restricted and Refed Rats

Abstract

Background: Sirtuins (SIRT1-7) have been implicated to mediate the beneficial effects of calorie restriction for healthy aging. While the physiological functions of SIRT7 are still poorly understood, SIRT7 has recently been shown to affect ribosome biogenesis, mitochondrial gene expression, and hepatic lipid metabolism. Objective: To analyze the effects of age and short-term calorie restriction (SCR) and subsequent refeeding on SIRT7 expression in key metabolic tissues. Methods: Four- and 24-month-old male Wistar rats were subjected to 40% SCR for 30 days, followed by ad libitum feeding for 2 or 4 days. Liver, white adipose tissue (WAT), heart and skeletal muscle samples were analyzed by real-time PCR and Western blotting for SIRT7 mRNA and protein expression, respectively. Results: Aging had diverse effects on SIRT7 levels in lipogenic tissues: both the mRNA and protein levels increased in the retroperitoneal depot (rWAT), did not change in the epididymal depot (eWAT), and decreased in the subcutaneous depot (sWAT) and the liver of old as compared to young animals. In the heart, extensor digitorum longus muscle (EDL) and soleus muscle (SOL), Sirt7 gene but not protein expression was lower in old than in young control rats. SCR did not affect SIRT7 expression in WAT and the liver in both age groups. In the heart of young animals, SCR did not affect SIRT7 mRNA or protein level. In EDL, SIRT7 protein but not mRNA levels decreased after SCR and remained reduced upon refeeding. In SOL, both SIRT7 mRNA and protein expression were inhibited by refeeding. In old rats, cardiac Sirt7 expression increased after SCR and refeeding. In old rats' EDL and SOL muscles, SIRT7 protein expression was inhibited by refeeding. Conclusion: Age-related changes of SIRT7 gene expression in key organs of energy homeostasis are tissue dependent.