Aging is a complex process that causes progressive deterioration of tissues and organs, leading to defects in tissue function, elevated vulnerability to stress, and death . The kidney is a target organ affected by aging-associated alterations, which are structurally manifested by tubular atrophy, interstitial fibrosis, and glomerulosclerosis (Guo et al., 2020). Moreover, the aging kidney undergoes functional changes with a notable decline in glomerular filtration rate (GFR), which is reported to be about 10% per decade after age 40 (Chou & Chen, 2021). With advanced aging, the kidney shows impaired ability to recover after acute kidney injuries, which

Background Aging is associated with impaired renal function and structural alterations. Oxidative stress plays a vital role in renal senescence and damage. Sirtuin 1 (SIRT1) is thought to protect cells from oxidative stress through nuclear factor erythroid 2-related factor 2 (NRF2). Ellagic acid (EA), a natural antioxidant, has been demonstrated to have renoprotective roles in vitro and in vivo. This study investigated if SIRT1 and NRF2 mediate the protective effects of EA in aged kidneys. Methods Male Wistar rats were divided into three groups including young (4 months), old, and old + EA (25 months). Young and old groups received EA solvent, while the old + EA group was treated with EA (30 mg/kg) by gavage for 30 days. Then, the level of renal oxidative stress, SIRT1 and NRF2 expression, kidney function parameters, and histopathological indices were measured. Results Treatment with EA significantly increased the level of antioxidant enzymes and reduced malondialdehyde concentration (P < 0.01). Moreover, EA administration remarkably upregulated mRNA and protein levels of SIRT1 and NRF2 as well as deacetylated NRF2 protein (P < 0.05). Additionally, EA treated rats improved kidney function and histopathological scores (P < 0.05). Conclusions These findings suggest that ellagic acid exerts protective effects on aged kidneys by activating SIRT1 and NRF2 signaling.