A Call to Action on Glucosepane
Advanced glycation endproducts (AGEs) are one of the root causes of aging. Many different types of AGE are created as a byproduct of ordinary metabolic operation and also arrive in the diet. Their levels rise and fall over time depending on circumstances and the body's efforts to clear out these unwanted compounds. The hardiest forms of AGE are a challenge, however: they lurk in your tissues in growing amounts as the years pass, disrupting important biological machinery, provoking chronic inflammation, and altering cellular behavior for the worse. Of these various types of AGE the most important by far in human tissues is glucospane, but very little attention is given to finding ways to break down and clear glucosepane from the body despite the consensus that this is a desirable goal.
So the SENS Research Foundation funds work on developing a glucosepane-clearing therapy, and is one of only two or three research organizations in the world to do so - and none of those programs are particularly large or active. The SENS work might be the largest glucosepane research program in the world at this point. Still, it looks like at least some other researchers are knowledgeable enough in this area to issue their own calls to action, and that is welcome, even when those calls to action are mild in comparison to those of the SENS program. A greater diversity of funding and more research groups focused on glucosepane can only be a good thing:
Advanced glycation end products (AGEs) represent a family of protein, peptide, amino acid, nucleic acid and lipid adducts formed by the reaction of carbonyl compounds derived directly or indirectly from glucose, ascorbic acid and other metabolites such as methylglyoxal. AGE formation in diabetes is of growing importance for their role as markers and potential culprits of diabetic complications, in particular retinopathy, nephropathy and neuropathy.Development of sensitive and specific assays utilizing liquid chromatography mass spectrometry with isotope dilution method has made it possible to detect and quantitate non-UV active AGEs such as carboxymethyl-lysine and glucosepane, the most prevalent AGE and protein crosslink of the extracellular matrix.
The results of [studies on AGE formation in two skin biopsies] show that while several AGEs are associated and predict complication progression, the glucose/fructose-lysine/glucosepane AGE axis is one of the most robust markers for microvascular disease, especially retinopathy, in spite of adjustment for past or future average glycemia. Yet overall little biological and clinical information is available on glucosepane, making this review a call for data in a field of growing importance for diabetes and chronic metabolic diseases of aging.
Glucosepane was originally the reason I looked so hard at the SENS foundation. They seemed to be the only people anywhere doing anything about it, and I was considering dedicating my donations to SENS to glucosepane projects. Later on, I changed my mind and decided to let the foundation spend it as they see fit, but that's only because I think they're going to be better at allocating the funding than I am, not because I don't think glucosepane is interesting.
The unfortunate reality is that there's been almost no work done in the field. My understanding is that one university has been able to reliably create glucosepane cross-links in the lab, and using that process, they're working on ways to easily detect the presence of glucosepane cross links. All this is very important, and being able to reliably work with the molecule will be crucial to finding ways to deal with it. But actually looking for enzymes to break it up is a long way off.