Comparative transcriptomics reveals distinct anti-aging specificities and functional complementarity among three...

Probiotics hold potential in delaying aging and promoting healthy aging. The systematic decline characteristic of aging limits single probiotic strain intervention to ameliorate aging. Multi-strain combination represents a promising strategy but lacks evidence-based criteria. In this study, Lactiplantibacillus plantarum Q7, Bifidobacterium animalis subsp. lactis F1-7, and Lacticaseibacillus paracasei J5 were selected based on their ability to extend both the lifespan and the healthspan of Caenorhabditis elegans. The three probiotic strains significantly enhanced anti-aging biomarkers in C. elegans. Transcriptomic analysis and validation revealed that all three strains co-regulated evolutionarily conserved Wnt signaling pathways while demonstrating distinct strain-specific characteristics. Specifically, L. plantarum Q7 modulated lipid metabolism and activated conserved longevity pathways, B. animalis F1-7 stimulated immune defense and protein stability regulation, and L. paracasei J5 predominantly influenced methionine metabolism and detoxification/antioxidation functions. The three-probiotic combination demonstrated superior anti-aging effects in C. elegans by both integrating single-strain pathways additively and activating the Wnt/Ca²⁺ pathway uniquely, thereby expanding the anti-aging regulatory network. This study underscores the necessity of employing combined probiotics to extend both lifespan and healthspan and provides a theoretical rationale for the design of functional complementarity probiotic formulations.