Effects of Gly-Low Supplementation on Long Term Health in Mice
The gly-low combination of common supplements is sold as GLYLO by Juvify Health, another of the supplement-focused spinout companies from the Buck Institute, an organization that should consider starting spinning out companies that are doing something more ambitious to treat aging as a medical condition. The scientifically interesting part of the underlying research is that inhibiting glycation to reduce methylglyoxal based advanced glycation endproducts (AGEs) appears, for reasons yet to be determined, to reduce appetite in mice. This leads to modest calorie restriction, and calorie restriction is well known to produce a broad range of benefits in short-lived species such as mice, including slowed aging and extended life span.
Are all of the benefits in mice reported to result from gly-low supplementation occurring due to calorie restriction? The researchers believe that other mechanisms are involved, but at present it is hard to argue definitively one way or another. A human trial is planned, though given that it will involve only obese individuals the outcome will be of little use as a comparison with effects in wild-type mice. Calorie restriction produces much larger effects on life span in mice than it does in humans, based on evidence to date. It is always interesting to have another point of comparison, provided it involves metabolically normal, relatively healthy older mice and humans.
Food overconsumption and obesity are also contributing factors to chronic hyperglycemia and enhanced glycolysis, which enhance the production of reactive a-dicarbonyls (a-DC's), such as methylglyoxal (MGO). MGO reacts nonenzymatically with biomolecules such as proteins, lipids, and DNA to form advanced glycation end-products (AGEs). These covalent adducts contribute to pathogenesis across several diseases by compromising protein function, forming extracellular crosslinks that disrupt tissue architecture, and modifying lipids and nucleic acids. Cellular protection against AGEs occurs by endogenous glyoxalase enzymes, which detoxify MGO and prevent AGEs formation. Given that increased sugar consumption, which drives obesity, is accompanied by enhanced glycolysis and concomitant production of toxic glycolytic byproducts, we hypothesized that detoxification of AGEs may be a viable therapeutic against obesity and its associated pathologies.
To develop a therapeutic for AGEs burden we utilized compounds previously reported to reduce MGO. In vitro treatment of N27 cells with alpha lipoic acid, nicotinamide, piperine, pyridoxamine, and thiamine was effective in rescuing neurite length retraction following exposure to MGO. The combination of these compounds, termed Gly-Low, displayed synergistic effects in protecting against MGO toxicity, and showed improvement compared to treatment with a single compound. In vivo treatment of C57BL/J6 control mice with Gly-Low resulted in significant lowering of body weights and food consumption compared to those on a control diet. Intraperitoneal injection of Gly-Low, as well as standard starving procedures, also reduced food consumption ruling out taste aversion as a potential caveat in reduction of food intake.
Administration of Gly-Low reduced food consumption and body weight, improving insulin sensitivity and survival in both leptin receptor deficient (Lepr db) and wildtype control mouse models. Unlike calorie restriction, Gly-Low inhibited ghrelin-mediated hunger responses and upregulated Tor pathway signaling in the hypothalamus. Gly-Low also extended lifespan when administered as a late life intervention, suggesting its potential benefits in ameliorating age-associated decline by inducing voluntary calorie restriction and reducing glycation.
I wonder how Caffeine compares (or in what ways this might be superior). From my own experience, eating is slightly repulsive, after a cup or two. More tools or sharper tools, I suppose.