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)


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.


And another thread from Pankaj Kapahi of UCSF/Buck Institute:

Why not just use metformin+taurine as anti-glycation instead? That’s what Bryan Johnson uses, and many ppl are deficient in taurine


That’s cumulative running hours, so it looks to me like yellow makes all the gains in the first 30 hours. Mostly in the first 18. But, Yellow never really sleeps, which is kind of bad. The control sleeps 12 hours at a time.

I’m actually taking all the ingredients in GLYLO, in much greater quantities. And Rapa. Yet I never feel like running on a wheel.


What are the ingredients of GLYLO?

See here: BAAM Presentations - GLYLO, and Meclizine mTORC1 Inhibitor

I may have spoken too soon. Unless I’m wrong that’s about a teaspoon of ground black pepper, and I may not get that much per day. Probably should buy that as a pill.

Didn’t somebody say that was a cyp3a inhibitor like GFJ? Probably not big enough to matter in the long run.