Combination therapy of glycation lowering compounds reduces caloric intake, improves insulin sensitivity, and extends lifespan

A new study on GLYLO, as mentioned previously here: BAAM Presentations - GLYLO, and Meclizine mTORC1 Inhibitor

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.

Unlike calorie restriction, Gly-Low is quite effective at extending lifespan even late in life, which might be in part due to improved metabolic flexibility as seen by improved insulin sensitivity

Full Paper:

2022.08.10.503411v1.full.pdf (312.8 KB)

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And an interview with the lead researcher and founder of the company that is a spin-out of The Buck Institute:

As a type 1 diabetic who, despite “well controlled” blood sugars, will live a shorter life, this is incredibly exciting. Given that complications are largely a result of AGEs, therapies to reduce AGE formation has huge potential to improve long-term outcomes.

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