More RAGE

I've posted on RAGE before, a cell receptor structure that binds to a range of biochemicals, including the undesirable advanced glycation endproducts or AGEs (hence RAGE - receptor for AGEs). RAGE binds to other materials too, and presumably has an important role in the normal operation of your tissue, but the accumulation of AGEs with age turns it into a problem.

Problems caused - or not helped - by AGE buildup include kidney disease, and the many variations of blood pressure and heart conditions caused by a lack of elasticity in the tissues of heart and blood vessels. Diabetics in particular suffer due to more rapid accumulation of AGEs based on their metabolic biochemistry (e.g. high blood sugar, inflammation, free radicals).

At least some of the degenerations brought on by AGE buildup can be laid at the feet of the interaction with RAGE, and the resulting actions then taken by your cells. Cell receptors are like keyboards or buttons - hit them with the right sort of molecules and you're instructing the cell to take action. Here are a couple of papers on RAGE and age-related degeneration:

RAGE and its Ligands in Retinal Disease

Ligands for RAGE, in particular AGEs, have emerged as relevant to the pathogenesis of diabetic retinopathy and age-related macular disease. While the understanding of RAGE and its role in retinal dysfunction with aging, diabetes mellitus, and/or activation of pro-inflammatory pathways is less complete compared to other organ systems, increasing evidence indicates that RAGE can initiate and sustain significant cellular perturbations in the inner and outer retina. For these reasons, antagonism of RAGE interactions with its ligands may be a worthwhile therapeutic target in such seemingly disparate, visually threatening retinal diseases as diabetic retinopathy, age-related macular degeneration, and proliferative vitreoretinopathy.

Let's work out how to interfere in the reaction of AGEs with RAGE, in other words, as it looks like this will help prevent or slow the onset of common causes of age-related blindness. More of thes same in the next paper:

Receptor for Advanced Glycation Endproducts (RAGE): A Formidable Force in the Pathogenesis of the Cardiovascular Complications of Diabetes & Aging

Unifying mechanisms for the consequences of aging and chronic diabetes are coming to light with the identification that common to both settings is the production and accumulation of the largely irreversible Advanced Glycation Endproducts (AGEs). AGEs impart multiple consequences in the tissues; a key means by which they exert maladaptive effects is via their interaction with and activation of their chief cell surface receptor, Receptor for AGE or RAGE.

Although the time course, rate and extent of AGE generation and accumulation in diabetes and aging may be distinct, unifying outcomes of the ligand-RAGE interaction in the vasculature and heart are linked to upregulation of inflammatory and tissue-destructive mechanisms.

Consistent with these concepts, administration of the ligand-binding decoy of RAGE, soluble or sRAGE, suppresses early initiation and progression of atherosclerosis in diabetic mice; suppresses exaggerated neointimal expansion consequent to arterial injury; and mitigates the adverse impact of ischemia/reperfusion injury in the heart. Importantly, the RAGE ligand repertoire upregulated in these settings is not limited to AGEs. The key finding that RAGE was a multi-ligand receptor unified the concept that in diabetes and aging, innate and adaptive inflammatory mechanisms contribute to the pathogenesis of tissue injury.

We all know just how bad chronic inflammation is over the years, don't we?

All that excess fat hanging around over the years generates [inflammation which generates] atherosclerosis, which then kills you.

Now neutralizing the AGEs with another biochemical that prevents them from triggering cellular RAGE is a good plan - but a better plan is to break down the AGEs and remove them from the body. Various groups are working on that. The presence of AGEs is an important difference between young and old tissue, and we should be working to repair any such significant difference as a part of developing true rejuvenation medicine.

Comments

Post a comment; thoughtful, considered opinions are valued. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.