Collaborative Effects of Caloric Restriction and Quercetin on Age-related Oxidative Stress Reduction through NQO1/Sirt1 Gene Regulation.

Abstract

Background: Aging is caused by the progressive accumulation of various changes in the body, which is associated with an increase in free radicals and oxidative stress (OS). The aim of this study was to investigate the potential of caloric restriction (CR) and quercetin (QUER) in alleviating OS in aging and the involvement of the NAD (P) H quinone oxidoreductase 1 (NQO1)/SIRT1 signaling pathway in these effects.

Methods: Two age groups of male Wistar rats (eight and 20 weeks of age) were included in the study and subdivided into normal diet (ND), ND with QUER (15 mg Kg^-1, IP), ND with CR, and ND with QUER and CR groups. The activities of catalase (CAT), paraoxonase (PON1), liver enzymes and lipid profiles, and the expression of SIRT1 and NQO1 genes were analyzed using the desired methods.

Results: We showed higher liver enzymes (aspartate aminotransferase [AST], alanine transaminase [ALT], and alkaline phosphatase [ALP]), increased atherogenic lipids, and reduced PON1 activity in 20-week-old rats compared with eight-week-old rats, and the administration of QUER and CR restored these values to the normal range. The expression of NQO1 and SIRT1 is also affected by CR and QUER. CR alone and in combination with QUER significantly raised the expression of the NQO1 and SIRT1 genes. This effect was notable in SIRT1.

Conclusions: QUER and CR together improved the detrimental effects of aging by modulating antioxidant signaling pathways, suggesting this combination is a complementary therapeutic regime for aging and age-related diseases.