Inhibition of the NF-κB and mTOR targets by urolithin A attenuates d-galactose-induced aging in mice

Urolithin A (Uro-A), an intestinal microbiota metabolite of ellagitannin, has anti-aging properties. Through the direct intake of ellagitannin (or ellagic acid) and strains capable of producing Uro-A, the transformation of Uro-A in vivo is a potential method to develop anti-aging preparations. Therefore, this study aimed to investigate the dose-response relationship between the colonic infusion of Uro-A and its anti-aging effects. Results indicated that Uro-A exhibited a dose-dependent anti-aging effect in the colon, and the minimum effective dose might be 3.0 mg kg(-1) day(-1). The main manifestations were that, compared with the model group, 3.0 mg kg(-1) day(-1) and 15.0 mg kg(-1) day(-1) of Uro-A can increase forelimb grip strength by 11.87% and 16.72%, respectively, and increase the discrimination index by 92.14% and 238.11%, respectively. Both doses effectively inhibited the D-galactose-induced increase in oxidative stress levels in the body, muscle atrophy, and neuronal apoptosis. Additionally, Uro-A released through the colon could alleviate D-galactose-induced aging in mice by inhibiting NF-kappa B and mTOR targets, providing significant protection for motor and cognitive functions. These findings provide a theoretical basis for future application and development of ellagitannin (or ellagic acid) in combination with strains capable of producing Uro-A.

Automated summary

Urolithin A (Uro-A) has dose-dependent anti-aging effects in the colon, with a minimum effective dose of 3.0 mg kg(-1) day(-1). Uro-A improves grip strength and discrimination index, inhibits oxidative stress, muscle atrophy, and neuronal apoptosis, and provides protection for motor and cognitive functions by inhibiting NF-kappa B and mTOR targets.