Oral microbiome-SASP-aging axis: mechanisms and targeted intervention strategies for age-related diseases.

Background: Global demographic aging is intensifying the burden of age-related diseases. Cellular senescence and the accompanying senescence-associated secretory phenotype (SASP) act as key drivers of disease progression by mediating chronic inflammation. As the second largest microbial community in the human body, the oral microbiome occupies a central position in systemic aging pathologies, and its dysbiosis and interaction with SASP are critical in this process. An imbalanced oral microbiota contributes to systemic chronic conditions via metabolic activities, virulence factor release, and immune system activation, while SASP serves as a central molecular mediator linking microbial dysbiosis to chronic inflammation, with well-recognized involvement in inflammatory bowel disease, bone disorders, and neurodegenerative conditions. Objective: This review aims to examine the mechanism by which oral pathogens directly modulate SASP secretion via microbial metabolites and virulence factors to drive the pathogenesis of age-related diseases, propose a unifying framework of the 'oral microbiome-SASP-aging' axis, summarize therapeutic interventions targeting this axis, and suggest future development directions for precise modulation of the 'microbiome-SASP-aging' cascade. Design: A narrative review was conducted to synthesize and analyze existing literature on the interplay between the oral microbiome, SASP, and age-related diseases. The review focused on mechanisms of oral pathogen-mediated SASP modulation, therapeutic strategies targeting the 'oral microbiome-SASP-aging' axis, and potential advancements in precise therapeutic delivery and combinatorial therapies. Results: The 'oral microbiome-SASP-aging' axis serves as a unifying framework for these pathologies. SASP inhibitors, probiotics, and traditional Chinese medicine (TCM) targeting this axis show promise for age-related disease management. Additionally, spatiotemporally precise delivery systems and probiotic-TCM combinatorial therapies are proposed for precise modulation of the 'microbiome-SASP-aging' cascade. Conclusions: The 'oral microbiome-SASP-aging' axis is a pivotal pathway driving age-related diseases. Therapeutic strategies targeting this axis hold significant promise for clinical management of these diseases. Future advancements in spatiotemporally precise delivery systems and combinatorial therapies are anticipated to enable precise modulation of the 'microbiome-SASP-aging' cascade, offering novel avenues for the prevention and treatment of age-related diseases.