Age, AGE and glucosepane
We are working on the Advanced Glycation Endproducts (AGEs). These are formed by reaction of sugars with proteins in the body, and accumulate with age. It is generally believed that some of them are bad for you – they cross-link proteins in tendons, blood vessel walls and skin to reduce elasticity and (probably) reduce the ability of stem cells to move and repopulate damaged tissue. The most common AGE cross-link identified so far is glucosepane. Our project is to find out exactly what glucosepane is doing, where it is, and (ideally) find a way of getting rid of it and opening up the tissue matrix for repair.
The idea of an ‘AGE_breaker’ compound is not new. Alagebrium cleaves a specific intermediate in the chemical pathway that creates AGE cross links in the body, and has been tried (unsuccessfully so far) as a drug for treaying age-related hypertension in man. There are two difficulties with creating AGE-breaker drugs. Firstly, AGEs are chemical targets, not genes or proteins. Almost all of pharmaceutical research over the last 40 years has been orientated to finding drugs that interact with proteins, and with the genes that make those proteins. So we cannot call on the trillions of dollars of research and technology development that have created the modern drug industry to help us (very much – we can use some of it). Secondly, AGEs are pretty stable and tough. That is inevitable – they are in essence the physiological equivalent of the black stuff on the bottom of your baking tin - what is left after years of use and the dishwasher. (In the case of humans, 'the dishwasher' is an array of mechanisms that take care of nearly all the waste products of metabolism.) We know how to break them quite easily, but only using a process that would also dissolve every protein in your body. The trick is finding a way to cleave them and leave all the rest of you intact.