Inflammageing is the chronic, low-grade, sterile, and systemic inflammation that progressively increases with age. Unlike acute inflammation, which is a temporary and protective immune response to injury or infection, inflammageing is a persistent, smoldering condition that damages tissues over time and acts as a significant risk factor for morbidity and mortality in the elderly.

Key Drivers and Mechanisms Inflammageing is driven by a complex interplay of biological failures:

• "Garb-aging" and Debris: The aging body loses its ability to clear cellular waste (autophagy and proteasome decline). This leads to the accumulation of "cellular garbage," such as damaged mitochondria and misplaced self-molecules (DAMPs), which trigger innate immune receptors like the NLRP3 inflammasome to release pro-inflammatory cytokines (e.g., IL-1β, IL-18).

• Cellular Senescence: "Zombie" cells that stop dividing but refuse to die accumulate in tissues. These senescent cells secrete a toxic cocktail of pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP), which spreads inflammation to neighboring healthy cells.

• Gut Dysbiosis: Age-related changes in the gut microbiome and increased intestinal permeability ("leaky gut") allow microbial byproducts to leak into the bloodstream, constantly stimulating the immune system.

Health Consequences Inflammageing is considered a central pillar of aging that fuels multimorbidity. It is causally linked to:

• Cardiovascular Disease (CVD): Chronic inflammation promotes atherosclerosis and heart failure. Residual inflammation (measured by hsCRP) is a strong predictor of recurrent cardiovascular events.

• Frailty and Sarcopenia: Elevated markers like IL-6, TNF-α, and CRP are associated with muscle loss and physical frailty. Recent studies suggest this association is significantly stronger in women than in men.

• Neurodegeneration: Systemic inflammation contributes to neuroinflammation, accelerating conditions like Alzheimer’s and Parkinson’s disease.

Interventions Strategies to counteract inflammageing focus on dampening this "slow burn":

• Lifestyle: Regular physical activity (both aerobic and resistance training) is proven to lower systemic inflammation. The 2025-2030 Dietary Guidelines emphasize fiber-rich whole foods and limiting ultra-processed foods to reduce inflammatory load.

• Targeted Therapeutics: Research is advancing on senolytics (drugs that clear senescent cells) and senomorphics (drugs that block SASP). Additionally, supplements like Urolithin A (which enhances mitochondrial cleanup via mitophagy) and Spermidine (which boosts autophagy) are showing promise in preclinical and clinical trials for improving cellular health and immune function.