Summary
Non-enzymatic reactions in glycolysis lead to the accumulation of methylglyoxal (MGO), a reactive precursor to advanced glycation end-products (AGEs), which has been hypothesized to drive obesity and aging-associated pathologies. A combination of nicotinamide, lipoic acid, thiamine, pyridoxamine, and piperine (Gly-Low), was identified to lower glycation by reducing MGO and MGO-derived AGE, MG-H1, in mice. Administration of Gly-Low reduced food consumption, lowered body weight, improved insulin sensitivity, and increased survival in both leptin receptor-deficient (Leprdb) and wild-type C57B6/J mice. Unlike caloric restriction, Gly-Low modulated hypothalamic signaling by upregulating mTOR pathway signaling to inhibit ghrelin-mediated hunger response. Gly-Low also slowed hypothalamic aging and increased survival when administered as a late-life intervention, suggesting its potential benefits in ameliorating age-associated decline by inducing voluntary caloric restriction and reducing glycation.
Competing Interest Statement
Lauren Wimer, Neelanjan Bose, and Pankaj Kapahi are patent holders of GLYLOTM, a supplenement licensed to Juvify Bio by the Buck Instutute. Dr. Pankaj Kapahi is the founder of Juvify Bio. The remaining authors have no conflicts of interest to declare. The remaining authors have no conflicts of interest to declare
Footnotes
This manuscript has been revised to reflect changes being formally peer reviewed by Cell Press.
