Abstract
Non-enzymatic reactions in glycolysis lead to the accumulation of methylglyoxal (MGO), a reactive precursor to advanced glycation end-products (AGEs), which has been suggested to drive obesity- and aging-associated pathologies. We observe that a combination of nicotinamide, lipoic acid, thiamine, pyridoxamine and piperine, which were selected to lower glycation (Gly-Low), reduce toxic glycolytic byproducts, MGO and MGO-derived AGE, MG-H1. Administration of Gly-Low reduced food consumption and body weight, improving insulin sensitivity and survival in both leptin receptor deficient (Lepr db) and wildtype C57 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.
Competing Interest Statement
Lauren Wimer and Pankaj Kapahi are patent holders of GLYLO, a supplement combination to lower glycation, licensed to Juvify Bio by the Buck Institute. Pankaj Kapahi is the founder of Juvify Bio. The remaining authors have no conflicts of interest to declare