Aging‐Related Renal Damage Is Associated with Decreased Klotho Expression and Increased Superoxide Production

Abstract

Klotho is a recently‐discovered anti‐aging gene. The purpose of this study was to determine changes in klotho, endothelin (ET) receptors, NADPH oxidases, and superoxide production in kidneys of aged rats. Twenty aged rats (male, 36 months) were divided into an impaired group (n=9) and an intact aging group (n=11) according to a cognitive function test. A group of 12 month‐old rats (n=10) was used as a young group. Plasma creatinine was significantly greater in the impaired group, suggesting impaired renal function. Aged rats showed a decrease in the number of glomeruli, an increase in collagen staining (fibrosis) around glomeruli and tubules, and an increase in periodic acid Schiff (PAS) staining (matrix remodeling) in and around glomeruli, indicating renal structural damage. These pathological changes were markedly aggravated in the impaired than in intact animals. Notably, aged rats demonstrated a significant decrease in klotho protein expression in renal cortex and medulla. Protein expression of interleukin‐6, Nox2 and ETA receptors and superoxide production were increased whereas MnSOD and ETB receptor expression were decreased in kidneys of aged rats. Interestingly, these changes were more pronounced in the impaired than in the intact rats. Conclusions: Aging‐related renal damage was associated with decreased klotho, increased inflammation, and increased superoxide production. Renal damage parallels with cognitive function impairment. Further studies are required to evaluate the role of klotho, ET receptors, and Nox2 and their relationship in aging‐related renal damage.