Unveiling mechanisms and potential application of probiotics in chronic inflammation and aging

Aging is a complex process marked by progressive functional decline and a chronic low-grade inflammatory state termed “inflammaging”, which together form a detrimental cycle that accelerates age-related decline. This state is characterized by an imbalance in pro-inflammatory cytokines (e.g., IL-6, TNF-α) and anti-inflammatory regulators (e.g., IL-10), driven by mechanisms such as oxidative stress, telomere attrition, and cellular senescence, with signaling pathways like NF-κB, JAK-STAT, Wnt/β-Catenin, and NFAT. Targeting the gut microbiome has emerged as a promising strategy to modulate this process, as age-related dysbiosis is a recognized hallmark of aging. Evidence indicates that specific probiotics and postbiotics can counteract inflammaging by restoring gut barrier integrity, reducing the translocation of pro-inflammatory endotoxins, and promoting the production of anti-inflammatory short-chain fatty acids (SCFAs) like butyrate. Clinically, probiotic supplementation has been shown to improve metabolic parameters (e.g., blood glucose and lipid levels), slow neurodegeneration by reducing β-amyloid accumulation, and modulate aging biomarkers such as telomere length. Despite promising outcomes, challenges remain in areas like strain- and individual-specific effects, along with dose standardization. Future efforts should focus on developing personalized probiotic regimens leveraging multi-omics technologies. This review systematically integrates cutting-edge developments in strain-specific mechanisms, preclinical and clinical evidence, and delivery system optimization, filling a gap in the field and providing theoretical reference for interventions in aging-related inflammation and the development of functional probiotics. Given their multi-target regulatory potential, probiotics represent a promising strategy for counteracting inflammation-associated aging.