L‐Tryptophan Produced by Bifidobacterium pseudocatenulatum NCU ‐08 Delays Aging in SAMP8 Mice by Activating the Sirt1/ P53 / P21 /Rb Signaling Pathway

ABSTRACT Gut microbiota delays aging by regulating the immune, metabolic, and neurological functions of the host. However, current research on novel probiotics with antiaging properties significantly lags, impacting their application in clinical treatments. In this study, metagenomics, culturomics, and probiotic property screening were used to identify Bifidobacterium pseudocatenulatum NCU‐08 as a potential probiotic with anti‐aging properties. In addition, B. pseudocatenulatum NCU‐08 effectively improved the behavioral characteristics, significantly reduced the levels of the age‐related protein β‐galactosidase (β‐gal) (BP: M = 0.81 vs. 1.13, p < 0.05), attenuated neuronal damage in the hippocampus, and improved the composition of the gut microbiota of senescence‐accelerated mouse tendency‐8 (SAMP8) mice. The targeted metabolomics suggested that L‐tryptophan (L‐Trp) may be a key substance for B. pseudocatenulatum NCU‐08 to exert anti‐aging effects (BP: M = 14878.6 ng/mL vs. 5464.99 ng/mL, p < 0.01). Mechanistically, using the aging model of SAMP8 mice and HT22 mouse hippocampal neuronal cells, it was found that B. pseudocatenulatum NCU‐08 might enter the intestine to regulate L‐Trp, and then transport it to the brain. In the brain, L‐Trp was metabolized to NAD + , which activated the Sirt1/P53/P21/Rb signaling pathway, thereby exerting antiaging effects. Interestingly, this antiaging effect was inhibited after the intervention of the Sirt1 inhibitor EX‐527. This study is the first to confirm the antiaging properties of NCU‐08 isolated from the fecal samples of seven centenarians in Jiangxi Province, providing data support for the future development of probiotic preparations with antiaging effects.