L-Aspartic acid is a Core Metabolite Mediating the Anti-aging Effect of Probiotics in Caenorhabditis elegans

The rapid expansion of the global elderly population underscores the critical need for effective interventions to delay aging. Probiotic supplementation has emerged as a promising strategy to extend lifespan, while the underlying mechanism remain poorly characterized. In this study, three probiotic strains ( Lactiplantibacillus plantarum Q7, Bifidobacterium animalis subsp. lactis F1-7, and Lacticaseibacillus paracasei J5) prolonged the lifespan of Caenorhabditis elegans by modulating metabolic homeostasis, including elevated NAD ⁺ /NADH ratios, reduced lipid accumulation, and increased ATP production. Through integrated untargeted metabolomics, L-Aspartic acid (L-ASP) was identified as a key mediator linking multiple pathways related to energy metabolism and amino acid metabolism. Exogenous L-ASP supplementation mimicked the beneficial effects of probiotics, extending the mean lifespan by up to 11.91% at the optimal concentration of 5 mM. Further genetic analyses revealed that got-1.2 functioned as the essential upstream regulator of endogenous L-ASP biosynthesis, while adk-1 served as the indispensable downstream effector of purine metabolism, thereby mediating L-ASP-induced longevity by optimizing energy metabolism. These findings establish a causal link between probiotic intervention and anti-aging phenotypes in C. elegans , positioning L-ASP as a critical metabolite for the regulation of healthy aging. This study provides a potential biomarker for the rapid screening of geroprotective probiotics, and offers a mechanistic basis for translating nutritional strategies into applications.