#612

I will aim to find the link later.

The results are mainly from my experimentation that I presented in a poster at the British Society for Research on Aging conference in September 2024 on which this web page is based.

https://citrate.science/2024poster/poster.html

I think of note and quite consistent is the rapid wound repair. Every week I have a blood draw and depending on citrate dosing and timing around the venepuncture it repairs in different timescales. One of the phlebotomists has asked me for some citrate because she is having an operation and wishes to repair as quickly.

Another thing that I am aware of is now my body is rebuilding. For instance the skin on my feet has been restructuring.

Now when you look at the research on the links between acetyl-CoA and gene expression it is clear that this is a possible mechanistic consequence. I don’t know what alternate approach would work.

There is a lot of research on citrate transport in and out of various cells which I have in a limited way summarised on the web page above. There is also research on ACLY. I am not the only person that thinks that the way cells recognise a high power availability is the cytosolic level of acetyl-CoA.

There is not that much research on citrate supplementation although there is a lot of experience with human beings using citrate in a medical environment normally in terms of blood transfusions and dialysis.

There is a drosophila result on citrate

I happen to think that they got the mechanism wrong.

In the end rapid wound repair is I think a good test of whether or not I am managing to change some of the key pathways of aging. I am not the only person to think that:

Impairment of wound healing is also linked with the aging process of skin, leading to a prolonged and impaired wound healing process. Thus, instead of the skin healing rapidly, it can progress a to chronic state that will increase the susceptibility of having wound infection and scarring.

This (and the restructuring of other skin) is in fact an example of maintenance and repair of the Extra Cellular Matrix which has rightly been discussed in another topic.

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#613

This paper is perhaps the key one that made me start looking at the links between the various acetyl-CoA pathways and gene expression.

https://www.nature.com/articles/s43587-021-00105-8

In this case acetate supplementation was used to directly affect acetyl-CoA levels. Acetate is metabolised by the ACSS2 (acyl-CoA synthetase) enzyme to acetyl-CoA. However, that particular pathway is one subject to homeostasis at a cellular level. Hence I use citrate which is subject to homeostasis in blood serum rather than the cytosol.

Strikingly, restoring cytosolic acetyl-CoA levels either by exogenous CiC expression or via acetate supplementation, remodels the chromatin landscape and rescues the osteogenesis defects of aged mesenchymal stem cells.

Arguably this gives a mechanism by which acetate supplementation can have a minor effect. I do a lot of indirect acetate supplementation, but it is citrate that has very obvious and very clear effects.

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#614

Thanks for the links. That mouse study is very interesting. The 1% dietary citrate, that was effective for some parameters, is equivalent to ingestion of about 5 g of citrate for a 70 kg adult human. How much citrate are you ingesting?

The fact that it had some beneficial effects on the mice is interesting, regardless of what caused those effects. It’s hard to say from the study whether the effects resulted from citrate uptake and increased production of acetyl-CoA increase or something else. The liver gene expression (see figure 4 o in the study) seems to have changed towards lower lipogenesis, which is the opposite to what one would expect with increased citrate, but the mice also lost weight, and that might explain lots of the benefits. It’s annoying when compounds result in weight loss because then it’s often hard to determine to what extent weight loss was a cause of the benefits rather than other effects of the compounds.

#615

So this is soomething you have seen several times after varying the dose of citrate so you are highly confident it’s the citrate having this effect, regardless of how it’s doing it?

The transport seems to be tightly regulated, as it should be with such substances that play a role in energy production. I expect it would be hard to bypass that by merely ingesting citrate. If that were possible to significant extent then I would expect to see some studies showing that exogenous citrate increases ATP production in cells. Have you seen any studies that show that citrate can increase ATP production?

#616

A lot of your questions are answered on this web page
https://citrate.science/2024poster/poster.html

If that were possible to significant extent then I would expect to see some studies showing that exogenous citrate increases ATP production in cells. Have you seen any studies that show that citrate can increase ATP production?

I don’t understand your reasoning for this. I personally would not expect exogenous citrate to increase ATP production.

There is a flow of ATP and citrate from the mitochondria. There are also transport proteins.

The levels of citrate in the body are managed in blood serum not the cell. This is important because acts as one of a number of mechanisms of blending the efficiency of cells effectively averaging out the biological age of individual cells.

#617

Here you go, that’s most.

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#618

Bryan Johnson’s
13 Powder Supplement mix.

If interested you could make your own batch. The 13 supplements are in the second photo.

Screenshot_20250322_130228_Facebook
Screenshot_20250322_130228_Facebook1080×2042 247 KB

Screenshot_20250322_130214_Facebook
Screenshot_20250322_130214_Facebook1038×1262 180 KB

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#619

Bryan says he’s not on TRT and gives his LH/FSH numbers.

https://x.com/bryan_johnson/status/1904188993836851634?s=46

Does anyone know if this is typical for long term CR? At least in the bodybuilding community, it’s well known that prolonged deficits are almost certainly going to result in a reduction in testosterone. Perhaps it rebounds after enough time?

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#620

I think you might be right with the people on large 25-30% or larger CR deficit level, but are you sure that is the case for people like Michael Lustgarten and Bryan Johnson on a more mild CR regime?

The recent gold standard, randomized, controlled trial does suggest that milder CR (at least for 2 years) would not lower people’s testosterone:

Effect of Calorie Restriction on Mood, Quality of Life, Sleep, and Sexual Function in Healthy Nonobese Adults

The CALERIE 2 Randomized Clinical Trial

Changes in luteinizing hormone, total testosterone, and follicle-stimulating hormone levels did not differ significantly between the groups

(Free testosterone dipped a bit at 12month, but was not different from controls after 24 months of CR)

The CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) trial was the first randomized controlled trial (RCT) of long-term calorie restriction in non-obese humans, funded by the National Institutes of Health (NIH)

The study was designed and conducted by top research institutions, including Duke University, Pennington Biomedical Research Center, and Tufts University, ensuring high scientific credibility and methodological rigor.

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2517920

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#621

Bryan’s new video on why he discontinued rapa. Not sure the mechanisms he explained are that accurate, but his conclusion for why he stopped taking rapa is fair IMO https://www.youtube.com/watch?v=MizVGCELs9Q

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Rapamycin sucks, DON'T TAKE IT
Bryan Johnson Rapamycin
#622

I haven’t watched the video, but I am happy he stopped taking or promoting rapamycin. I’m with Matt Kaeberlein on this - having BJ be associated with rapamycin or promoting it would be a big negative. That said, BJ deserves credit for stopping a drug that he feels is contrary to his health - admitting you made a mistake is valuable and reflects well on him.

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#623

It might upregulate PCSK9 among other things for some, which is anti-longevity.

Bryan is a Hero.

#624

Ok I get it, rapa messes with the immune system and Johnson says it messes with NK cells and they are the cancer fighters. OK fair enough, I’ll buy it. But the cute little mice are notorious for dying of cancer. If immunity/cancer was the risk why hasn’t that shown up in the hyper-sensitive mice?

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#625

The other markers are “real” and important, but I’ve got those hammered thru statins/ezetimide metformin/dapa and other tricks. Those other markers are so low that even if rapa is raising them somewhat I’m still way low. I’m willing to take a small hit on “important” markers as long as they’re still “low enough” in my judgement. Maybe he’s not.

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#626

He says his main issue was with HRV which decreased during sleep. Sleep is his number one thing, so from his perspective if he really has narrowed this down to the rapamycin it makes sense.

#627

And to be cynical and look at monetary motivations, Brian Johnson is starting the hyperbaric thing, which I think will be great. I’m looking forward to trying it, and it will be a valuable contribution to the longevity community. He also has the morning shake product, which I’m sure is very good, and a quality brand of olive oil, which is hard to find. So, monetarily, he’s got this whole longevity ‘ecosystem’ that runs on money. Having a weird cousin like rapamycin hanging around his neck is a major distraction. He’s got a clear ‘path,’ and having weird, uncontrollable things popping up is counterproductive to his business model.
And now, time for a limerick:
There once was a man, Brian J,
Who banished rapamycin today.
With shakes, oil, and air,
He’s building a fair,
No strange brews may crash his soiree

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#628

So despite the clickbait title Bryan Johnson provides zero evidence that rapamycin accelerated his aging during the period he was taking it. And if he was actually the slowest aging human in the world as he claims, then it’s overwhelmingly unlikely that rapamycin was negatively impacting his aging process.

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#629

Please do better, he did say his glucose dropped, high cholesterol was corrected, and soft tissue infections went away.

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#630

I would appreciate more specifics around the cholesterol. Given that his ApoB/LDL are discordant, I’d be curious what exactly changed about his lipids without rapamycin.

It’s interesting that he noted a RHR increase with Rapamycin, has anyone else noticed that?

I wouldn’t be surprised if his dose was too high when combining with CR and all of his other mTOR inhibiting interventions.

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#631

Even if rapamycin was worsening a few biomarkers for him, that doesn’t mean it was accelerating aging.

Cherry-picking four markers out of thousands proves nothing. If a compound extends lifespan, it’s slowing aging at the systemic level—by definition. Rapamycin has done that across multiple mammalian species. But sure, go with the guy calling it “poison.”

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