Caloric Restriction Mitigates Kidney Fibrosis in an Aged and Obese Rat Model

Abstract

Caloric restriction is an effective intervention to protract healthspan and lifespan in several animal models from yeast to primates, including humans. Caloric restriction has been found to induce cardiometabolic adaptations associated with improved health and to delay the onset and progression of kidney disease in different species, particularly in rodent models. In both aging and obesity, fibrosis is a hallmark of kidney disease, and epithelial–mesenchymal transition is a key process that leads to fibrosis and renal dysfunction during aging. In this study, we used an aged and obese rat model to evaluate the effect of long-term (6 months) caloric restriction (−40%) on renal damage both from a structural and functional point of view. Renal interstitial fibrosis was analyzed by histological techniques, whereas effects on mesenchymal (N-cadherin, Vimentin, Desmin and α-SMA), antioxidant (SOD1, SOD2, Catalase and GSTP1) inflammatory (YM1 and iNOS) markers and apoptotic/cell cycle (BAX, BCL2, pJNK, Caspase 3 and p27) pathways were investigated using Western blot analysis. Our results clearly showed that caloric restriction promotes cell cycle division and reduces apoptotic injury and fibrosis phenotype through inflammation attenuation and leukocyte infiltration. In conclusion, we highlight the beneficial effects of caloric restriction to preserve elderly kidney function.

The Effects of Caloric Restriction on Inflammatory Targets in the Prostates of Aged Rats

“…The evaluation by Western blot analysis of the protein content of a key antioxidant enzyme, SOD1, revealed that CR enhanced the expression of SOD1. We can speculate that the latter finding may be a response signal by which CR protects prostate tissue against oxidative stress, as already reported in [79,80]. Recently, Scordino and colleagues described Hsp70/SOD1 signaling against oxidative stress damage [81].…”