fig1

Figure 1. IDM conceptual framework. Life-course determinants drive four core pillars of inflammaging (cellular senescence, immunosenescence, gut dysbiosis, and mitochondrial dysfunction), leading to chronic systemic inflammation and organ-specific multimorbidity clusters, with organ-level pathology feeding back to further amplify systemic inflammation, forming a self-reinforcing feedback loop. IDM: Inflammaging-driven multimorbidity; ACEs: adverse childhood experiences; SASP: senescence-associated secretory phenotype; NF-κB: nuclear factor κB; LPS: lipopolysaccharide; TLR4: Toll-like receptor 4; mtDNA: mitochondrial DNA; cGAS: cyclic GMP–AMP synthase; STING: stimulator of interferon genes; ROS: reactive oxygen species; IL-6: interleukin-6; TNF-α: tumor necrosis factor-alpha; CRP: C-reactive protein; IL-1β: interleukin-1β; DAMPs: damage-associated molecular patterns; CKM: cardiovascular–kidney–metabolic.