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Aging‐associated renal dysfunction promotes the pathogenesis of chronic kidney disease. Mitochondrial dysfunction in renal tubular epithelial cells is a hallmark of senescence and leads to accelerated progression of renal disorders. Dysregulated calcium profiles in mitochondria contribute to aging‐associated disorders, but the detailed mechanism of this process is not clear. In this study, modulation of the sirtuin 1/angiotensin II type 1 receptor (Sirt1/AT1R) pathway partially attenuated renal glomerular sclerosis, tubular atrophy, and interstitial fibrosis in D‐galactose (D‐gal)‐induced accelerated aging mice. Moreover, modulation of the Sirt1/AT1R pathway improved mitochondrial dysfunction induced by D‐gal treatment. Transient receptor potential channel, subtype C, member 3 (TRPC3) upregulation mediated dysregulated cellular and mitochondrial calcium homeostasis during aging. Furthermore, knockdown or knockout (KO) of Trpc3 in mice ameliorated D‐gal‐induced mitochondrial reactive oxygen species production, membrane potential deterioration, and energy metabolism disorder. Mechanistically, activation of the AT1R/PKA pathway promoted CREB phosphorylation and nucleation of CRE2 binding to the Trpc3 promoter (−1659 to −1648 bp) to enhance transcription. Trpc3 KO significantly improved the renal disorder and cell senescence in D‐gal‐induced mice. Taken together, these results indicate that TRPC3 upregulation mediates age‐related renal disorder and is associated with mitochondrial calcium overload and dysfunction. TRPC3 is a promising therapeutic target for aging‐associated renal disorders. [ABSTRACT FROM AUTHOR]

Aims: Visceral obesity is a major health issue and is a risk factor for an atherogenic state. Visceral obesity has been reported to be a crucial link between albuminuria and cardiovascular diseases (CVD). This study attempted to explore the association between visceral obesity and albuminuria in prediabetic individuals. Methods: This cross‐sectional study included 24871 prediabetic participants over 40 years of age from seven centres across China (REACTION study). The visceral adiposity index (VAI) was determined based on the measurements of anthropometric indices and lipid parameters. Increased albuminuria was defined as a urinary albumin‐creatinine ratio (UACR) ≥30 mg/g, indicating kidney damage. Propensity score matching was used to reduce bias, and a multiple logistic regression model was performed to evaluate the association between visceral obesity and albuminuria in the population with prediabetes. Results: Participants with increased UACR exhibited increased VAI, age, blood pressure, triglycerides, poor glycaemic control, CVD events, and decreased estimated glomerular filtration rate (eGFR). Multiple logistic regression analysis demonstrated that VAI quartiles were positively associated with an increased risk of albuminuria (Q2: odds rate [OR]: 1.10, 95% confidence intervals [CI] 0.96–1.25; Q3: OR: 1.16, 95% CI 1.01–1.32; Q4: OR: 1.26, 95% CI 1.10–1.44, p for trend = 0.001). Stratified analysis revealed that the association of VAI level with increased albuminuria risk also occurred in people who were young, women, overweight or obese, with poor control of blood pressure, and eGFR ≥90 ml/min per 1.73 m2. Conclusions: Visceral obesity assessed by VAI is significantly associated with increased UACR in a Chinese population with prediabetes. [ABSTRACT FROM AUTHOR]