Calorie-restriction treatment mitigates the aging in rat liver model.

Abstract

The aging process promotes progressive impairment of homeostasis and the increase of the risk of disease and death. A major hallmark of the aging process is the systemic chronic inflammation which strongly contributes to the onset of aging-related diseases. In the liver, the aging condition drives the hepatocytes to develop a metabolic dysfunction-associated steatosis. Caloric restriction (CR) is a remarkable strategy to delay biological aging, occurring through several mechanisms. In this study we aimed to explore, employing an in vivo rat model, the impact of CR on aging-mediated liver inflammation markers. The experiments were performed on 14 male Sprague-Dawley rats (24 months old). At 18 months old, rats were allocated into two groups: the normal diet (ND) group was continued ad libitum diet, and the CR regimen group was fed a diet of the same chow restricted to 60% of the intake. All animals were sacrificed at 24 months old. Compared to the ND group, morphological examination of the liver revealed a lower level of fibrosis in the CR group, concomitantly with a reduced expression of key fibrotic markers, such as collagen I, fibronectin, and αSMA. Furthermore, CR improved the liver oxidative balance, as showed by the increased expression of two scavenging enzymes, SOD1/SOD. Moreover, we reported concomitant reduction of NLRP3 inflammasome signalling. Interestingly, CR significantly improved the signalling of key members of the nutrition-sensitizing affected by aging, AMPK/SIRT1/LKB1. Collectively our findings support the evidence on the metabolic benefits of CR about aging-related liver inflammation, by inducing a morphological improvement that mirrors the decrease in the expression of inflammatory molecular markers.