Glucosamine and aged mice

 

It would appear that glucosamine, the arthritis neutraceutical, promotes longevity.

D-Glucosamine supplementation extends life span of nematodes and of ageing mice

This paper is a mix of C. elegans and mouse work. Most of the findings are reasonably transferable but the core finding, that a metabolite of glucosamine inhibits glycolysis, was actually demonstrated in the worm section. Extended longevity was found both in C. elegans and ready-aged mice.

Glycolysis inhibition and life extension in C. elegans:

And for longevity in already aged mice:

It's worth noting that glucosamine usage in humans is observationally associated with extended lifespan.

To me the core finding is that the inhibition of glycolysis extends life. I like that. In the mice it was also found to cause insulin resistance, mild at the dose rate used in the paper. However I would expect resisting insulin to be associated with extending lifespan. I'm quite keen on extending my own healthspan. The longer this goes on, the happier I'll be. My plan is resist insulin.

Now. Is there any other simple way of inhibiting glycolysis which might rival extended glucosamine administration?

If we go to Veech's isolated, perfused, working rat hearts (again) we can see some interesting things:

I suppose the first thing we have to say is that the heart works quite well on the utterly non physiological substrate of isolated glucose.

Next is that insulin decreases glycolysis compared to this baseline. The increased glucose ingress to the cell is diverted to glycogen synthesis while insulin simultaneously increases the efficiency of the electron transport chain. So net flux through glycolysis drops from 5.6 to 3.8 micromol/min/ml. Ketones (a physiological mix of AcAc and BHB) drop glycolysis from the baseline 5.6  down to 1.7micromoles/min/ml, which I find quite impressive.

As always, Veech maintains a phobia about fat so we have no data about what the addition of fatty acids might do to glycolysis. Enough said that ketones suppress it quite well. Veech has a detailed discussion of the various redox couples which control this process. To a simpleton like myself we can just view the situation as observing when ketones flood the TCA with acetyl-CoA there is nowhere for glycolysis products to go to, so it stops. The effect of redox couples on the energy yield of ATP hydrolysis is a separate consideration.


Let's summarise: Ketone bodies markedly inhibit glycolysis. Note to push-biking self: They also promote glycogen formation.


Glucosamine drops glycolysis in C. elegans by 43% and gives a measurable longevity gain. Ketones in an isolated perfused working rat heart drop glycolysis by 66% and appear, in many papers, to have some favourable effects on many of the problems which come to us with age. I find that interesting.

Peter

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