Inflammaging: Mechanisms, Therapeutic Strategies, and Implications for Age-Related Diseases

Purpose: This review synthesizes current mechanistic understanding of inflammaging pathophysiology, with particular emphasis on cellular senescence, mitochondrial dysfunction, and aberrant innate immune regulation. Furthermore, it evaluates novel therapeutic modalities targeting these molecular pathways and examines their clinical relevance for cardiovascular pathology, neurodegenerative conditions, metabolic disorders, and oncological diseases.
Materials and Methods: A comprehensive narrative review was conducted examining primary literature from 2000 to 2025, focusing on molecular mechanisms including senescence-associated secretory phenotype (SASP), mitochondrial damage-associated molecular patterns (mtDAMPs), and macrophage polarization dynamics. Therapeutic interventions were evaluated based on preclinical and clinical evidence, including senolytic compounds, metabolic interventions, and biologic agents.
Results: Cellular senescence drives inflammaging through the SASP, wherein senescent cells secrete pro-inflammatory cytokines, chemokines, and proteolytic enzymes via NF-κB, C/EBPβ, and mTOR signaling cascades. Mitochondrial deterioration releases mtDAMPs and reactive oxygen species, activating NLRP3 inflammasome and cGAS-STING pathways. Macrophage functional reprogramming toward pro-inflammatory phenotypes amplifies these responses. Clinically, elevated inflammatory biomarkers predict morbidity and mortality in aging populations, with the CANTOS trial establishing causality between IL-1β-mediated inflammation and cardiovascular events. Therapeutic strategies demonstrate promise: senolytics (fisetin, dasatinib/quercetin) selectively eliminate senescent cells; mTOR inhibitors modulate SASP; metabolic interventions including caloric restriction improve immune cell function; and targeted biologics reduce systemic inflammation.
Conclusion: Inflammaging represents a fundamental biological process bridging cellular senescence to systemic disease pathology. The intricate interplay among senescent cells, mitochondrial impairment, innate immune dysregulation, and chronic low-grade inflammation establishes the pathological foundation underlying major age-related diseases. Emerging therapeutic approaches including senolytics, metabolic interventions, and precision biologics demonstrate considerable potential for healthspan extension and reduction of age-associated disease burden. Future investigations must refine intervention protocols, establish optimal timing for therapeutic initiation, develop comprehensive biomarker panels, and implement precision medicine strategies in geroscience. (Open J Biomed Res 2025;4:18-23)