$20,000 For a Plan to Remove Buildup of the AGE Glucosepane

The SENS Foundation recently teamed up with InnoCentive to spur movement in the development of AGE-breakers for human use. I'd mentioned this over at the Longevity Meme, but the initiative seems worth more time and attention than just a link. So here we are: but what is an AGE-breaker, and why should we care? In short, it has been known for some time that one of the unpleasant changes that takes place with aging is the accumulation of advanced glycation endproducts, or AGEs, in our biochemistry:

Your body needs certain proteins in order to work properly; the creation of AGEs involves taking two or more of these proteins and sticking them together with chemical gunk, preventing them from doing their jobs. This is known as crosslinking; day in and day out, it is taking place in your body. Some AGEs are short-lived but common, growing or declining in population in response to your diet and metabolic peculiarities. Others are very long-lived or impossible for the body to break down; they build up over the years, and eventually there's enough of this gunk to seriously damage you. 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).

You can read more on the topic at the SENS Foundation: dealing with AGE crosslinks is one of the seven facets of the SENS program.

A few earnest efforts to establish drugs capable of safely breaking down AGEs have taken place in past years, such as the development of ALT-711 or alagebrium. This sort of treatment has great promise: if medical science can clear out AGEs on a regular basis, then their contribution to the aging process can be eliminated entirely. Unfortunately the only meaningful progress resulting from work to date is the discovery that AGEs in laboratory animals are quite different from those in humans: age-breakers like ALT-711 that showed results in rats have gone nowhere in human trials.

However, researchers have identified the most important AGE in humans, a chemical called glucosepane:

In the extracellular matrix of the skin of a non-diabetic 90-year-old, glucosepane accounts for about 50 times the protein cross-linking as all other forms of protein cross-linking.

Sadly, very few scientists are working in any way on an AGE-breaker for glucosepane. The only group I know of is Legendary Pharmaceuticals, which is a very small outfit indeed. This is a state of affairs very familiar to anyone who spends much time looking into the science of human aging and the potential for engineered longevity: a great deal is known about what needs to be done, but, aside from the field of regenerative medicine, next to nothing is being done.

This is where non-profits like the SENS Foundation or Methuselah Foundation enter the picture: working to raise awareness, spur interest, persuade scientists, and generate research funding. In the case of glucosepane, the SENS Foundation has branched out to work with InnoCentive, a company with an interesting business model: they are a marketplace for people in search of cost-effective solutions to specific problems in life science development, biotechnology, and engineering (amongst other areas of endeavor). This, I imagine, works for these fields because (a) any laboratory is capable of a wide range of tasks touching upon its specialty, (b) the state of play is so dynamic and broad that someone outside a particular specialty is going to find it hard to dig up the right connections for a very specific need. A marketplace of this sort allows laboratory managers and experts to find new buyers for their talents and products, and buyers to find what they need at a better price - or at all, in some cases.

So if you look through the InnoCentive challenges, you'll see things ranging from speculative RFPs to prizes offered for processes yet to be developed by biotechnologists - but which could be, sometime soon.

The SENS Foundation has dipped into this marketplace in search of the development path to an AGE-breaker for glucosepane, and a kick in the pants for the research and development community who should already be working on the problem:

As a biomedical charity, SENS Foundation's usual method for tackling research problems is to provide direct grants for expert researchers to do critical-path work in rejuvenation science. So we have long had an open Request for Proposals (RFP) for qualified researchers to tackle this problem, addressing specifically the most important of those crosslinks - a stubborn AGE called glucosepane. To date, we've had no takers.

That's why we've launched this $20,000 Theoretical Research prize - not to demonstrate the breakage of glucosepane in the lab, but to give us a clear enough roadmap for the project that we can attract the further financial and scientific resources needed for a full-scale research and development project. ... SENS Foundation is reaching out to InnoCentive's network of more than 200,000 Solvers: in the next 60 days, give us a detailed working plan to develop a drug to give aging arteries their youthful spring, and averting age-related disease and pathology.

To be a supporter of engineered human longevity is to be frustrated by the large difference between what might be and what is. We'd like to see a small army of researchers working to develop repair technologies for issues such as glucosepane buildup, and there is no good reason as to why that army doesn't yet exist. But it doesn't exist. At least regenerative medicine and stem cell research is a going concern, and far beyond needing our help, but still: the present state of longevity science is a long, long way from where we'd like it to be.

There is a great deal of work left to do, and initiatives like the SENS Foundation/InnoCentive effort are a step in the right direction.

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