Sirtuin 1 (
SIRT1)
enzyme plays a pivotal role in the regulation of many physiological functions. In particular, it is implicated in ageing-related diseases, such as
cardiac hypertrophy,
myocardial infarct, and endothelial dysfunction; moreover, its expression decreases with age. Therefore, an effective strategy to extend the lifespan and improve cardiovascular function is the enhancement of the expression/activity of
SIRT1 with exogenous agents. The Citrus
flavonoid naringenin (NAR) presents structural similarity with the natural
SIRT1 activator
resveratrol. In this study, we demonstrate through in vitro assays that NAR significantly activates
SIRT1 enzyme and shows antisenescence effects. The binding mode of NAR into
SIRT1 was detailed investigated through in silico studies. Moreover, chronic administration (for six months) of NAR (100 mg/kg/day) to 6-month-old mice leads to an enhancement of
SIRT1 expression and a marked reduction of
reactive oxygen species production in myocardial tissue. Furthermore, at the end of the treatment, the plasma levels of two well-known markers of cardiovascular
inflammation, TNF-α and
IL6, are significantly reduced in 12-month-old mice treated with NAR, as well as the cardiovascular risk (total
cholesterol/HDL ratio) compared to control mice. Finally, the age-associated fibrotic remodeling, which is well detected through a Mallory trichrome staining in the vehicle-treated 12-month-old mice, is significantly reduced by the chronic treatment with NAR. Moreover, an improvement of myocardium functionality is highlighted by the enhancement of
citrate synthase activity and stabilization of the mitochondrial membrane potential after NAR treatment. Taken together, these results suggest that a nutraceutical approach with NAR may have positive impacts on many critical hallmarks of myocardial senescence, contributing to improve the cardiac performance in aged subjects.