SENS5 Video: Talking About AGEs and Aging

Advanced glycation end-products (AGEs) such as glucosepane are what you might think of as a sort of biological rust. They build up as an undesirable side-product of the chemistry of life and damage important molecular machinery in and around cells by sticking to molecules or sticking molecules together, making it impossible for them to do their jobs. The increase in AGE levels in the body with advancing age isn't a matter of straight accumulation over time - it's more dynamic than that, and the level of AGEs in the diet may play some role - but eventually it becomes enough to cause serious harm. Aging is little more than damage, and AGEs are one form of that damage.

The SENS Foundation is currently sponsoring research into therapies to break down glucosepane, what is probably the most important AGE in humans. I see that the UK-based research group has a few web pages devoted to their work, on one of which is offered some explanation as to why the drug industry isn't all that much help when it comes to building ways to tackle AGEs:

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.

Here is a recently posted video from last year's SENS5 conference in which one of the research groups focused on AGEs discusses their work:

Advanced glycation end-products are a class of natural products that form non-enzymatically on exposed protein residues in the human body. AGEs accumulate as a result of normal metabolism and aging, and significant elevations in these molecules have also been observed in the plasma of patients with chronic diseases, such as diabetes, cancer, arthritis, cardiovascular disease, and others. Our laboratory is taking an orthodox approach to studying these materials; we have initiated a synthetic program to prepare AGE- adducts on large scale and in chemically homogenous form. This talk will describe ongoing efforts along these lines, with a particular focus on exploring a class of arginine-derived AGEs. Chemical and biological insight arising from these studies will also be discussed. It is our hope that this small molecule-based strategy will serve to shed new light on the role of AGEs in both healthy and disease physiology.
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