Frontiers in Pharmacology · Oct 31, 2026
Bazi Bushen Capsule Delays Aging-Aggravated Progression of Diabetic Kidney Disease via Attenuating Renal Tubular Epithelial Cell Senescence
By Lini Gao, Yunlong Hou, Mengnan Li et al.
Background: Aging is one of the important risk factors for diabetic kidney disease (DKD). Previous studies have largely focused on the relationship between accelerated renal aging induced by stress-related injury factors and DKD, whereas systematic research on the impact of natural aging on renal susceptibility to DKD remains lacking. Methods: Normal control and DKD mouse models were established in young and aged mice at different months of age. A 2 × 2 factorial design was used to compare renal structure, function, and senescence-related markers and to determine the key role of age in DKD progression. Using aged DKD mice and a cisplatin-induced HK-2 cell senescence model in vitro, we investigated whether BZBS could exert renal protection by delaying cellular senescence and explored the underlying mechanisms. Results: Two-way ANOVA showed that hyperglycemia had significant main effects on renal injury indicators, histopathology, and senescence-related markers. Age had significant main effects on kidney index, albuminuria, fibrosis, p21, and γ-H2AX, and some indicators showed an age × diabetes interaction. Under hyperglycemic conditions, aged DKD mice exhibited more severe renal tubular injury, interstitial inflammation, and fibrosis than young DKD mice, and p21-positive cells were mainly located in renal tubules. These findings suggest that natural aging enhances renal susceptibility to DKD injury and that senescence occurs mainly in renal tubular cells. BZBS effectively reduced the levels of renal injury markers in aged DKD mice and alleviated tubulointerstitial inflammation and fibrosis. This protective effect of BZBS was associated with the attenuation of renal tubular epithelial cell senescence, which was closely linked to improved mitochondrial function and reduced oxidative stress and DNA damage. Conclusion: Renal tubular epithelial cell senescence may contribute to the age-related exacerbation of DKD-related renal injury. BZBS attenuates this senescence and provides a new strategy and experimental evidence for the prevention and treatment of DKD.