#41

Mr. Skeptic says: Take a few cheap ingredients, combine them, get a patent, advertise, then charge a lot.

#42

I agree.
Very inexpensive ingredients. Guarantee you that it won’t give significant weight loss which is why they throw in the 16 hour fast. I want to see an RCT where they just give the product without fasting advice. It won’t outperform the controls.

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#43

Double skeptic. Makes the world go round. Or just propose a holy grail theory with a pet molecule. You just have to “apply” for a patent, not actually be granted, and spin the marketing. Getting a patent granted in the US is a 5-10 yr journey. Targeting a very rich and sick society
gold mine

#44

“Getting a patent granted in the US is a 5-10 yr journey”
True, I read in a business magazine long ago, that “patent pending” was a much more powerful deterrent to competitors, as initial patent applications are full of broad scope claims that may be limited in the final patent.

#45

Read patent’s and copy for own self use. Yes, I shamelessly do this.

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#46

This is a link to the preprint of the full paper regarding Gly-low extending median and maximum lifespan:

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#47

Only hype at this time.
I already had NAC and glycine so I will add some Bioperine and up the doses a little.

“August 13, 2022. The copyright holder for this preprint(which was not certified by peer review) is the author/funder”

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#48

Meclizine (Dramamine Less Drowsy, Bonine) was mentioned by Dr. Miller , along with astaxanthin, in the podcast below:

Click, “show more” and scroll down to time stamps:

1:12:13

#49

Looking at the slide "Piperazines are specific mTORC1 inhibitors, to the left of the red circle is testosterone propionate. It performs as well as rapamycin for mTORC1, and elevates mTORC2 less than all others. Testosterone propionate was discontinued, because it has a short half life, and because there are better options. It was not discontinued due to safety concerns, or low efficacy.

On the right chart, meclizine performs better than cinnarazine, with slightly higher mTORC2 elevation.

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#50

Mac, I agree. I don’t do my high intensity interval training for fun either. It is painful which is probably why I don’t see anyone else my age at the gym doing it. They probably think an older guy like me should slow down to avoid a bone-breaking fall or a heart attack. My thinking is to give it all I’ve got while I still can. And, so far, no broken bones, strokes, or heart attacks. Besides, there are people at the gym trained to help with problems like that, assuming it’s not a “widow maker.”

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#51

Count me as a skeptic, too. Amazon has 600+ customer reviews of GLYLO. I read through a mixture of these, especially those who didn’t rate it either a 1 or a 5 because I figure ratings of 2,3 and 4 may be more realistic opinions. Whatever the case, this product won’t be on my list.

#52

Yeh, just make your own by taking the supplements individually.

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#53

Does anyone know how good mTORC1 inhibitors piperazines are compared to rapamycin. Is there a good list of mTORC1 inhibitors?

#54

This is the best summary of on-market mTOR inhibitors that I’ve seen (the presentation I went to in Berkeley, CA (UC Berkeley) last spring.

Here is a paper the covers many of the mTOR inhibitors currently being used and new ones being tested (with the goal of treating cancer, but of course, these can also likely be used as longevity drugs as rapamycin and everolimus are used):

There have been quite a number of startup companies that have formed over the past few years focused on mTOR inhibitors for anti-aging
 rapamycin, but without the side effects. At least one came out of the Buck Institute, and was later shut down I believe, due to lack of success. Others are still going and have raised many tens of millions of dollars in VC money to fund their development and testing efforts. Its a hot area given the success of rapamycin :

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#55

My thought about mTOR inhibition is that inherently it would come with side effects. In particular I would expect it from time to time to increase cytosolic ROS which would be why there are examples of cankers and rashes.

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#56

Why, specifically, do you say this. Have you any specific research papers that have identified the mTOR inhibition with cytosolic ROS?

Most of the side effects (though not canker sores, or rashes I think) are currently thought to be linked to the eventual inhibition of mTORC2 that happens with ongoing, daily dosing of rapamycin over weeks or months.

See this thread: Evidence that mTORC2 inhibition is detrimental, by Dudley Lamming

#57

The key is mTOR inhibition encouraging autophagy and mitophagy and improving the quality of the mitochondria.

I then started with this paper
https://www.nature.com/articles/s43587-021-00105-8

It seems to me that some of the positive effects of Rapamycin are similar to the effects of Janus Kinase inhibitors and are as a result of SLC25A1 operating the non-canonical TCA cycle more effectively and its interplay with NF-ÎșB.

here’s a paper about that:
https://www.nature.com/articles/s41586-022-04475-w

If the mitochondria are in a better state (through this particular route) then the additional flow through SLC25A1 enables also the generation of ROS in the Cytosol.

This paper looks at that

These are papers I have hunted up on the net. AFAIK Cysotolic ROS being part of inflammation is established science and there are loads of papers about this.

My own hypothesis in this tends to bring these things together and I published this on my blog.

I link to the relevant papers in that piece.

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#58

Kaempferol is an mTORC1 inhibitor.

Conclusion: The study exhibited that Kaempferol had a better binding affinity towards the receptor FKBP12, a Rapamycin Binding Domain and AKT serine/threonine-protein kinase resulting in its better efficacy in the mTORC1 inhibition as when compared with standard drug Everolimus against HCC. To the best of our knowledge, no studies have been reported on Kaempferol as mTORC1 inhibitor against Hepatocellular carcinoma.

Kaempferol is also a calcineurin inhibitor. (I bought some cumin tincture to mix with the hair grower, instead of tacrolimus and cyclosporine.

https://iubmb.onlinelibrary.wiley.com/doi/pdf/10.1002/iub.94

Highest natural sources of Kaempferol are capers and cumin, followed by cloves and caraway. Capers have 104.29 mg/100g, versus cumin 38.6 mg/100g.

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