Inflammaging and age-related multimorbidity: from shared biological mechanisms to therapeutic opportunities

More than 60% of adults aged 65 years and older live with two or more chronic conditions, yet current healthcare systems remain largely organized around individual diseases. This mismatch between the biological complexity of aging and disease-specific clinical practice raises the core question of whether there are shared mechanisms underlying multimorbidity. Emerging evidence indicates that inflammaging, characterized by chronic low-grade inflammation associated with biological aging, may represent an important common biological context linking cardiovascular disease, type 2 diabetes, neurodegenerative disorders, depression, sarcopenia, and other age-related conditions. In this narrative review, we synthesize current evidence on four interconnected processes associated with inflammaging - cellular senescence, immunosenescence, gut dysbiosis, and mitochondrial dysfunction - and examine their potential contributions to distinct patterns of organ-specific multimorbidity. We further discuss how life-course exposures, including adverse childhood experiences and cumulative socioeconomic disadvantage, may shape inflammatory and biological aging trajectories long before the clinical manifestation of disease. Based on these findings, we propose an inflammaging-driven multimorbidity framework that integrates shared inflammatory mechanisms with stratified therapeutic opportunities, including senolytic and anti-cytokine strategies, lifestyle interventions, and digitally enabled integrated care. This framework provides a mechanism-informed perspective for understanding multimorbidity and may help guide the development of more comprehensive and human-centered prevention and management.