# AGE-RAGE axis

The AGE-RAGE axis is an inflammation-driving signaling loop. It starts when advanced glycation end products (AGEs), and other ligands, bind a receptor called RAGE (coded by the AGER gene). RAGE is not picky. Beyond AGEs, it binds S100/calgranulin proteins, HMGB1, amyloid-beta, and certain protein fibrils. When a ligand binds, it switches on cascades (NADPH oxidase, MAP kinases, NF-kB). Those drive sustained pro-inflammatory and pro-oxidant gene activity in your blood-vessel cells, macrophages, and neurons. There is a nasty twist: NF-kB also makes more RAGE, creating a self-amplifying loop. The axis is implicated in diabetic blood-vessel damage, atherosclerosis, kidney disease, and neurodegeneration. It is seen as one mechanistic bridge between high blood sugar, oxidative stress, and the chronic low-grade inflammation of aging.

## Sources

- Ramasamy R, Yan SF, Schmidt AM. (2011). Receptor for AGE (RAGE): signaling mechanisms in the pathogenesis of diabetes and its complications. Annals of the New York Academy of Sciences. https://doi.org/10.1111/j.1749-6632.2011.06320.x
- Yan SF, Ramasamy R, Schmidt AM. (2009). The receptor for advanced glycation endproducts (RAGE) and cardiovascular disease. Expert Reviews in Molecular Medicine. https://doi.org/10.1017/S146239940900101X
- Schmidt AM, Yan SF, Yan SD, Stern DM. (2010). The RAGE Axis: A Fundamental Mechanism Signaling Danger to the Vulnerable Vasculature. Circulation Research. https://doi.org/10.1161/CIRCRESAHA.109.212217

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