Elevating acetyl-CoA levels reduces aspects of brain aging

I wish you success! I hope you are able to advance aging research and longevity.

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It definitely does something. Exactly how much and exactly how to handle the side effects is another issue. However, I do weekly blood tests for myself and I am at the forefront of the protocol. CRP at under 0.16mg/L, Cystatin C at 0.89 mg/L and HbA1c at 4.18% (much that this probably excludes the labile part) are quite positive biomarkers.

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And all whilst eating not particularly healthy full English breakfast and not exactly holding back on the booze - you must be doing something right!!!

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I think you are right in your analysis. I am focussing on the biochemistry. I am still careful about how much I eat, but the balance of what I eat is not what would be considered an orthodox longevity diet.

Similarly I do some exercise on an exercise frame (not particularly good chinups and failures of pullups etc), but apart from brisk walking I probably only do about 5 minutes of exercise a day.

Last night was the first drinking night for a week, however. I will compare the blood test I did yesterday to the one I had last friday to see if I can identify any changes (particularly on urate). I am likely to go back on the wagon, however. Although I do have a rather tempting half bottle of nice port sitting around.

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Hi, is there any news on your patent?

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I have done this. Thanks. I now supplement with mag, potassium and calcium citrate. I’ve stopped all other supplements containing magnesium and potassium. I added calcium for oxylate binding (I take with meals).

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The key questuon is how much citrate.

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Not much. Not yet. But I’ve laid the foundation. What’s the minimum effective dose?

I don’t think you will see much before at least 2g, but really you want quite a bit more than that. I tend to run at 20g per day split into four doses of 5g. It is important to spread out the dosage as citrate is rapidly metabolised by the liver. Today I had citrate at 7am, 9.20, 10.20 and will have it at around noonish.

However, it is important to get into it gradually and possibly top up your melatonin as well.

The most I have had in a day (on an experimental basis) was 70g.

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Thank you. I’ll start planning for it now. 2g to start, spread throughout the day. Add some melatonin. The spreading part will be the hard bit.

Melatonin at night. I would not spread 2g. If you take 2g quantities at different times that is ok. There is a serum cytosol concentration gradient that needs to be sufficient.

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Thanks. Good clarification. 2g citrate in AM. Add more at different time later as I build up. Melatonin if I wake up in middle of night (not what you said but my plan).

I haven’t been hitting the minimum effective dose of citrate but will starting soon.

Taking melatonin during the night is good. Watch the sleep cycles.

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Doesn’t increased acetyl open up heterochromatin, which should ideally stay quiet? Heterochromatin DNA is also less likely to get damaged. Sure you increase gene expression with more acetyl…

I also raised some realistic concerns about increase citrate intake from the cancer side of things. Personally, I don’t have any reason to even consider citrate intake, actually I switched my magnesium from Mg Citrate to Mg Gluconate for the very reason of inhibiting it.

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I responded to this on the other thread.

The acetylation of the histone with acetyl-CoA is needed for genes to be transcribed into mRNA. Without that they don’t function. That is IMO one of the core pathways of the aging phenotype. (failed transcription which then results in methylation which then reduces either attempts to transcribe or the speed of transcription).

My guess is methylation probably slows down transcription which would reduce the numbers.

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BRCA/fasting inhibits ACC1 (ACC1 turns on from citrate and is how citrate signals fed/overnutrition state). AMPK also inhibits ACC1. Citrate signals high-nutrition which is bad.

[see dayan goodenowe talk happening rn, he’s recording it]

I know citrate/INDY1 mutants were how one of morten’s grad students demonstrated increased survival in the case of a really weird gene knockout (not representative of most people).

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John,

Please contact me off the forum - dr-frasers-office@grantfrasermd.com

I’m really interested in your thought process and protocol. The ability to learn from smart people who are keenly interested in this space is a bonus. I really like this forum. It is such an opportunity to expand my range of possible - but with careful evaluation of the evidence, risk and benefits.

Looking forward to hearing from you John. I’d like to see your protocol, and what the rationale is behind it, along with the evidence that made you select the things you did.

Regards,

Grant Fraser, M.D.

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