RAGE is the receptor for advanced glycation end-products (AGEs), the mechanism by which cells react to the presence of AGEs. AGEs are metabolic byproducts that are both created in the body and present in the diet; cooking animal fat produces AGEs, for example. Diets heavy in meat and the related, fun, unhealthy products so prevalent in this modern calorie-packed world of ours are also heavy in AGEs of various sorts. It remains a topic for discussion as to the degree to which dietary AGEs are a problem, however. Do they contribute significantly to the issues caused by AGEs in general, or only in conditions in which metabolism is already aberrant, such as metabolic syndrome and type 2 diabetes? Opinions differ.

There are two quite distinct classes of harm associated with AGEs in aging. The first, and not the topic of today's research, is the creation of persistent cross-links in the extracellular matrix by the AGE glucosepane. A cross-link shackles together two of the complex molecules the extracellular matrix, thereby altering its properties by preventing free movement of those molecules. Significant cross-linking degrades elasticity, strength, and other necessary properties of various tissues. In the case of blood vessels, this loss of elasticity leads to hypertension and consequent cardiovascular disease. Glucosepane cross-links cannot be effectively broken down by our biochemistry, and thus will have to be dealt with via some form of therapy.

The second form of harm associated with AGEs is chronic inflammation. Chronic inflammation causes disarray and damage throughout the body, degrading tissue maintenance and encouraging dysfunction in organs and biological systems. AGEs produce inflammation in part by their interaction with RAGE, triggering it relentlessly and thus spurring other inflammatory signaling. The more AGEs there are in circulation, even if they are short-lived varieties, easily dealt with by the body, the more inflammation. Metabolic disorders of obesity, such as the aforementioned metabolic syndrome and type 2 diabetes, are characterized by excessive AGEs and excessive inflammation - though it is worth noting that there are plenty of other ways by which excess fat tissue generates inflammation.

Here, researchers demonstrate that the burden of inflammation and resulting organ damage occurring due to a raised level of AGEs is reduced when RAGE is disabled. The study uses normal and genetically engineered mice lacking RAGE, the mice fed either a normal diet or a diet containing large amounts of dietary AGEs. To the point I raised above about opinions on the effects of dietary AGEs, choice of diet didn't make much difference here. But RAGE knockout mice are better off in old age in either case, most likely due to reduced inflammatory consequences arising from the AGE-RAGE interaction.

Knockout of receptor for advanced glycation end-products attenuates age-related renal lesions