Fermented Pomegranate Juice with Lactiplantibacillus plantarum CCFM1286 Attenuates Brain Aging in Association with PINK1/Parkin Activation

Abstract Urolithins, gut microbiota-derived metabolites of ellagic acid, demonstrate potential in mitigating aging-related physiological decline. This study investigated the neuroprotective effects and mechanisms of pomegranate juice fermented with Lactiplantibacillus plantarum CCFM1286 (CCFM1286FPJ) in mice with D-galactose-induced brain aging. CCFM1286FPJ intervention significantly improved aging-related anxiety-like behaviors, attenuated hippocampal neuronal damage, and lowered systemic inflammation. Mechanistically, CCFM1286FPJ suppressed glial activation, thereby inhibiting p53/p21 and p16 senescence-associated pathways and restoring BAX/Bcl-2 balance to suppress caspase-3-dependent apoptosis. Furthermore, CCFM1286FPJ promoted autophagy and induced PINK1/Parkin-mediated mitophagy. Serum metabolomics revealed the enrichment of pomegranate-specific metabolites, including punicic acid and urolithins, and identified modulation of tryptophan metabolism and the tricarboxylic acid cycle, implicating these pathways in the amelioration of neuroinflammation and the restoration of energy homeostasis. These results indicate that CCFM1286FPJ counteracts brain aging, potentially through multiple mechanisms involving fermentation-derived bioactives.