Yeast-Displayed GDF11 and Oral Delivery

    Through the work of Steve Perry, it appears that taking growth differentiation factor 11 (GDF11) provides definite health benefits and some evidence of rejuvenation.  However, GDF11 is a very large molecule, weighing in at 45,091 Daltons (more than 8x the size of insulin), and up to now it has seemed that the only feasible delivery mechanism is subcutaneous injection.  For some of us, that requirement and the arcane dilution, storage, and dose-determination procedures are show-stoppers.

    However, as Perry recently pointed out, now there appears to be a new way of avoiding all that complication by simply taking a pill.  A paper published by Song, et al. on May 23, 2022 in the journal Biogerentology  (LINK) describes how mice were fed genetically-modified yeast that was programmed to express GDF11 on its surface, and that the resulting yeast-displayed rGDF11 somehow managed to get into the mouse bloodstream, as indicated by blood testing.  The GDF-treated mice had significantly extended health-span and life-span.  There is also evidence of GDF11 senolytics, in that the population of senescent cells in the liver and kidneys of the treated mice was significantly reduced.  It is not at all clear how the huge GDF11 molecule makes the transition from gut to bloodstream, but somehow that seems to be happening with some efficiency.

   One would like to try this method of GDF11 delivery on humans.  Oral delivery would avoid all of the complications of injection and open GDF11 treatment to a much wider spectrum of the health-seeking population.  Yeast is normally considered safe, thereby avoiding FDA roadblocks.  Is genetically-modified yeast treated the same way?

    So the question is, how easy would it be for our present array of supplement suppliers to provide us with this GDF11 yeast product?  They would need to either reproduce the work described in the paper or obtain a culture of these GDF11-expressing gene-modified yeast cells from the experimenters, whose work was done in China.

    Yeast cells are self-reproducing.  (That's how the brewing industry works.)  Given such a starter-culture, the supplier could in principle brew their own from there on. This yeast delivery method also suggests that other large-molecule drugs like insulin for Type-1 diabetics might be delivered without the need for injection.  Many doors may be opened by this development.

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  • The issue I see with that is that the yeast is going to make an unpredictable amount of gdf11 and that is an issue because gdf11 is very potent and so overdosing is a real concern. It could kill you if you took too much and too much is a very small amount. I just dont see any way you could control the yeast to only make a desired amount of around 100pg.

    Personally, I have been taking gdf11 for 3 years and the injecting is a bit of a hassle at first but you get used to it and it becomes no big deal.  The good news is you only have to take it for a few months or shorter and you are essentially topped off and can stop taking it. So it isnt an endless series of daily injections for life. A monthly single booster is often all that is needed. I am very happy with the effects, but having said that it isnt a silver bullet, just another tool in the arsenal.

      • JGC
      • JGC
      • 2 mths ago
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      Fred Cloud 

           NOTE: The permissions on my link to the paper above were set wrong, but I think that is now fixed.

          Yes, dosing is a problem, but all that means is that one has to be careful not to take too much.  Even with the GDF11 delivered by injection there is an unknown variable: What fraction of the subcutaneous injection actually reaches the bloodstream, and does that fraction vary with injection site?

          In the the yeast experiment, they gave the treated mice a fixed amount of food containing the GDF-yeast derivative, then allowed them to eat an unlimited amount of untreated food.  None of the mice showed symptoms of GDF11 overdose or died from that.  The experiments were not flying blind, because they were using an antibody test to determine the GDF11 concentration on blood samples.

          Perhaps the low bioavailability of yeast-delivered GDF11 kept the blood dosage low.  In any case, the dose level the mice received seemed to have benefited them dramatically.

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      • Jay Orman
      • Jay_Orman
      • 12 days ago
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      Fred Cloud I would like to hear more about your experience with GDF11 if you don't mind sharing. The site looks interesting, but hearing someone's personal experience is much better. Thanks.

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  • Fred, could you share amount of GDF11 you has been taking monthly?

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