Inflammaging is Not the Cause - It's the Result | Dr Luigi Ferrucci

Inflammaging represents a chronic, low-grade inflammatory state driven primarily by the accumulation of cellular damage rather than spontaneous immune dysfunction. While intrinsic immune dysregulation prevents older individuals from "shutting down" inflammatory responses as efficiently as the young, the root cause lies in damaged macromolecules and mitochondrial failure. When mitochondria become compromised, they leak DNA and cardiolipin into the cytoplasm, triggering the inflammasome and pathways like NF-kB and STING, which release potent cytokines such as IL-6 and IL-18. Furthermore, intestinal permeability allows bacterial fragments to enter circulation, compounding the systemic response. Because this damage is never fully repaired, inflammation remains perpetually activated as a secondary messenger. Effective intervention requires prioritizing damage limitation—through antioxidant-rich diets, smoking cessation, and metabolic support—rather than simply blocking inflammatory markers, which has shown inconsistent results in clinical trials like CANTOS.