NCU-08 ameliorated senescence modulation of the AMPK/Sirt1 signaling pathway and gut microbiota in mice.

Aging is a degenerative disease in which organisms and neurological functions decline. Emerging research has underscored the vital role of the gut microbiota in age-related processes. However, the identification of aging-associated core microbiota remains limited. In this investigation, we isolated a strain of NCU-08 from the feces of centenarians and assessed its impact on aging using a mouse model induced by D-gal. Our study revealed the exceptional probiotic attributes of NCU-08. Administration of NCU-08 significantly ameliorated age-related memory impairment, motor dysfunction, and anxiety-like behaviors in aging mice ( < 0.01). Moreover, tissue staining analysis demonstrated that NCU-08 reduced the intensity of SA-β-gal-positive in the hippocampus of aging mice. It also reversed pathological damage and structural abnormalities in brain and intestinal tissue. NCU-08 inhibited neuroinflammation induced by TLR4/NF-κB ( < 0.01) and preserved the blood-brain barrier integrity by activating the AMPK/Sirt1 pathway ( < 0.05). Furthermore, it mitigated neuronal apoptosis and oxidative stress by upregulating the PI3K/AKT signaling pathway ( < 0.01) and enhancing the activities of antioxidant enzymes, including GSH-Px ( < 0.01), SOD ( < 0.01), and CAT ( < 0.01). Besides, analysis of 16S rRNA sequencing data demonstrated that treatment with NCU-08 restored intestinal microbiota homeostasis after senescence. It enhanced the abundance of beneficial bacteria while suppressing the growth of pathogenic microorganisms. In summary, our study unveiled that this novel strain of NCU-08 exerts anti-aging effects through regulating the AMPK/Sirt1 pathway and intestinal microbiota. It holds promise as a functional food for promoting anti-aging effects and offers a novel approach to address aging and associated metabolic disorders.