Life Extension and Glycation in Nematodes

A most interesting report drifted into my sphere of notice today; a way of boosting life span in nematode worms. We are complex machines, built from a constantly recycling pool of component proteins built into intricate structures and systems; when proteins become damaged, that is wear and tear - grit in the works, the onset of aging, loss of function and the degenerations that lead to death.

Protein degradation and malfunction is a major cause of ageing and can be the result of attacks on proteins by other molecules. One of these processes, called glycation, involves the spontaneous attack by sugars on proteins. If glycation gets out of hand many proteins are degraded or destroyed – proteins which are important for the proper functioning of the body. Protection against glycation declines with age leading to increasing glycation damage with increasing age. A critical enzyme involved in protection against glycation is "Glyoxalase 1". Using a model nematode system, Professor Paul Thornalley (University of Warwick) and his collaborators at the University of Heidelburg have shown for the first time that by enhancing levels of glyoxalase I the glycation process can be diminished and life can be extended by up to 40%. Similarly, by decreasing amounts of the enzyme they have shortened the lifespan of the nematodes. Professor Thornalley will present the results at the Society for Experimental Biology's Annual Main Meeting on Sunday 1st April.

"This work shows for the first time that this enzyme also protects proteins against damage by oxidation and nitration", says Professor Thornalley. The enzyme works by converting the damaging reactive products of glycation derived from glucose into harmless compounds. "This implies that glycation promotes multiple types of protein damage in ageing"

You might be familiar with "advanced glycation endproduct" or AGEs, a class of damaging compounds that build up in the body over the years and that lead to some forms of progressive loss of function. As one might espect, the process of formation for these compounds starts with glycation - more glycation, more AGEs. In effect, AGEs are one portion of the root cause of aging. Scientists have shown promising results in animals with anti-AGE drug candidates (such as ALT-711) over recent years, but humans have very different types and proportions of AGEs than even other, shorter-lived mammals.

One can hope that the result quoted above will be repeated up the chain of animal models in the years ahead, and glyoxalase (or something similar, derived from this branch of research) will prove beneficial to humans. The odds are it'll end up in the same bucket as ALT-711 and a range of other compounds, however - a lot of different compounds are tested and fail for every one that even makes it to the "promising but near miss" category. It doesn't pay to get too excited about studies in nematode worms. Wait until the mice at least.

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