Aging and Disease · 2026
Oral Dysbiosis and the Hallmarks of Aging: A Perspective on Mechanisms and Therapeutic Opportunities
Aging is characterized by progressive decline in cellular and tissue functions, markedly increasing susceptibility to age-related diseases (ARDs) such as neurodegenerative diseases, cardiovascular diseases, metabolic diseases, and musculoskeletal disorders. The twelve aging hallmarks proposed in 2022 have clarified the underlying mechanisms linking aging to ARDs. As the second-largest microbiome in the body, oral dysbiosis has been associated with aging-related phenotypes and may influence systemic aging and ARDs. Available evidence, derived largely from observational and preclinical studies, suggests that oral dysbiosis may be associated with selected aging-related processes, including cellular senescence, altered intercellular communication, mitochondrial dysfunction, and loss of proteostasis via virulence factors, metabolites, etc. Here, we summarize epidemiological observations linking oral microbiota to ARDs, and offer a perspective centered on core aging hallmarks to delineate how oral dysbiosis may serve as a plausible modulator of systemic aging and ARD progression. We also introduce promising interventions such as plaque control, targeted antimicrobials, and probiotics as research opportunities. Finally, we discuss current limitations and highlight future directions including microbial biomarkers and machine learning-based aging prediction models to identify whether oral microbiota related biomarkers can improve risk stratification and mechanistic studies of biological aging.