In our previous interview with Dr. Kapahi, we discussed his work examining how advanced glycation end products (also known as AGEs) drive the aging process. Since we last spoke, Pankaj has been hard at work trying to identify compounds that can rein in the deleterious impact of AGEs, primarily by lowering levels of methylglyoxal. Methylglyoxal is formed as a side product of the breakdown of sugars, and is involved with the formation of AGEs, so it is a logical molecular target here. In his screening process of over 800 compounds, he managed to find five compounds which, when combined, had synergistic protective effects against methylglyoxal toxicity.
This powerful combo now makes up the product GLYLO, and preliminary testing of GLYLO in rodent models revealed, sure enough, that the combo reduced glycolytic byproducts, improved insulin sensitivity, extended lifespan by 30-40% when administered late in life, and reduced caloric intake, and promoted weight loss. Importantly, this effect was shown to be independent of peripheral hormones like leptin and ghrelin. In fact, injecting ghrelin into mice treated with GLYLO did not result in increased energy intake - suggesting that GLYLO was changing how the hypothalamus responded to ghrelin. In other words, reducing methylglyoxal, through GLYLO, appeared to be lowering their body fat set point.
