Caloric restriction inhibits renal artery ageing by reducing endothelin-1 expression

Abstract

Background: The renal artery plays a central role in renal perfusion and is critical for proper renal function. Ageing is an independent risk factor for both impaired renal function and vascular disorders, and associated with an increase in the expression of the vasoconstrictor endothelin-1 (ET-1), and caloric restriction (CR) without malnutrition has been shown to be an effective inhibitor of renal dysfunction induced by ageing. The objective of this study was to determine whether CR-mediated alleviation of renal dysfunction is mediated by ET-1 expression.Methods: The young (2 months, 2 M) and old (12 months, 12 M) Sprague-Dawley male rats were used and fed ad libitum. The 12-month-old rats were further divided into 12 M and 12 M-caloric restriction (CR) (30% calorie restriction). After 8 weeks, the renal tissues were showed by PAS staining, and age-related metabolic parameters and renal functions were detected in each group of rats. The inflammatory cytokines of interleukin (IL)-6, IL-1β, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1 (TGF-β1) were analyzed using ELISA. The mRNA and protein expression in the renal artery were analysis by qRT-PCR and Immunoblot analysis.Results: Ageing was associated with significant increases in 24 h urine protein content and serum triglyceride and cholesterol in 12 M rats, both of which were significantly inhibited in 12 M-CR. The mRNA expression and the secretion of IL-6, IL-1β, TNF-α, and TGF-β1 in the renal artery was significantly increased with ageing and inhibited by CR. CR also inhibited ageing-induced Edn1 (encoding ET-1) mRNA and protein expression in the renal artery. In addition, CR could regulate ET-1 expression by inhibiting the activation of NF-κB signaling and activation and induction in the expression of NF-E2-related factor 2 (Nrf2) and histone deacetylase and gene repressor sirtuin 1 (SIRT1), both of which play a central role in mitigating oxidative stress in young rats.Conclusions: Moderate CR can reverse the ageing related kidney dysfunction by reducing the ET-1 expression. CR might be used as an alternative to prevent the ageing induced renal artery dysfunction.

Sex Specific Differences in Response to Calorie Restriction in Skeletal Muscle of Young Rats

“…Furthermore, no downstream effects of IκB and NF-κB were observed. Both IL6 levels, a key inflammatory marker, and the decrease in response to CR observed in the current study are in agreement with results from previous studies [11,33]. Finally, we were not able to detect any changes in markers of senescence.…”

“…Conversely, there was a decrease in IL6 levels and an increase in NF-κB in females. Previous reports have shown that CR decreases key inflammatory mediators in several tissues, including skeletal muscle (11,30,32,33). It should be noted that most of our results are indirect measures of inflammation.…”

Ageing, cellular senescence and chronic kidney disease: experimental evidence

“…There are nutrient signalling regulators, which can regulate ageing-related diseases and promote health. Numerous studies show that caloric restriction (CR) prolongs lifespan in laboratory animals [68,69]. Moderate CR can be used to halt the agerelated kidney dysfunction by inhibiting the endothelin-1 (ET-1) expression [68].…”

“…Numerous studies show that caloric restriction (CR) prolongs lifespan in laboratory animals [68,69]. Moderate CR can be used to halt the agerelated kidney dysfunction by inhibiting the endothelin-1 (ET-1) expression [68]. In aged mice, physical exercise reduces triacylglycerol and restores plasma lipids homeostasis by regulating lipid metabolism [70].…”

Sex Specific Differences in Response to Calorie Restriction in Skeletal Muscle of Young Rats

“…On the contrary to the results in males, there was a decrease in IL6 and NF-κB protein levels in younger CR treated female rats. Previous reports have shown that CR decreases key inflammatory mediators in several tissues, including skeletal muscle [ 11 , 35 , 37 , 38 ]. It should be noted that most of our results are indirect measures of inflammation.…”