The term "inflammaging" was coined by Claudio Franceschi in 2000 to describe a specific phenomenon: the chronic, low-grade, systemic inflammatory state that increases with age and is strongly associated with virtually every major age-related disease. Unlike acute inflammation — which is protective, targeted, and self-limiting — inflammaging is persistent, diffuse, and destructive.
Why Inflammaging Develops
Multiple overlapping mechanisms drive the development of inflammaging. Senescent cells — cells that have stopped dividing but remain metabolically active — secrete a chronic inflammatory signal (the SASP) that activates immune cells and creates sustained low-level inflammation throughout the body. Accumulated cellular debris from impaired autophagy activates pattern recognition receptors of the innate immune system, producing chronic inflammatory signaling. The gut microbiome shifts with age toward pro-inflammatory species, increasing intestinal permeability and systemic exposure to bacterial products like LPS that directly activate inflammatory pathways. Declining sex hormones — particularly estrogen in women and testosterone in men — lose their anti-inflammatory effects, allowing inflammatory tone to increase.
The Disease Connections
Cardiovascular disease: Atherosclerosis is fundamentally an inflammatory disease. CRP, IL-6, and other inflammatory markers predict cardiovascular events independently of LDL cholesterol — and the JUPITER trial demonstrated that statin therapy reduced cardiovascular events primarily through its anti-inflammatory effects (CRP reduction), not just LDL reduction. Inflammaging is the background inflammation on which cardiovascular disease develops.
Neurodegeneration: Microglia — the brain's immune cells — become chronically activated in inflammaging, producing neuroinflammation that directly drives Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. The amyloid hypothesis of Alzheimer's is being progressively reframed as an inflammatory hypothesis in which amyloid accumulation is partly a response to chronic neuroinflammation.
Cancer: Chronic inflammation creates a tissue environment permissive to malignant transformation — promoting angiogenesis, suppressing immune surveillance, and providing growth signals for transformed cells. The majority of cancers develop in chronically inflamed tissue.
Evidence-Based Anti-Inflammatory Interventions
Diet: The Mediterranean dietary pattern — highest vegetable and fruit intake, olive oil as primary fat, fish 2–3x weekly, minimal processed foods and added sugar — reduces hsCRP by 20–30% and IL-6 meaningfully in multiple RCTs. The anti-inflammatory effect is mediated by polyphenols, omega-3 fatty acids, and fiber (which feeds anti-inflammatory gut bacteria).
Exercise: Acute exercise produces transient inflammation — then, in recovery, drives a substantial anti-inflammatory response mediated by IL-6 released from muscle tissue. Chronically, regular exercise reduces baseline inflammatory markers, including hsCRP and IL-6, through multiple mechanisms including improved body composition, improved insulin sensitivity, and direct immune modulation.
Omega-3 fatty acids (EPA/DHA): The most evidence-based nutritional anti-inflammatory intervention. EPA and DHA are precursors to resolvins and protectins — lipid mediators that actively resolve inflammation. 2–4g daily of EPA+DHA reduces triglycerides, reduces inflammatory markers, and at higher doses reduces cardiovascular events (REDUCE-IT trial).
Hormone optimization: Estrogen and testosterone both have direct anti-inflammatory effects. Estrogen reduces NF-κB activation and IL-6 production. Testosterone reduces inflammatory cytokine production in macrophages and monocytes. Declining sex hormones are a direct driver of inflammaging — and hormone optimization is among the most mechanistically targeted anti-inflammatory interventions available.