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.
AnUser
#617
Here you go, that’s most.
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Agetron
#618
Bryan Johnson’s
13 Powder Supplement mix.
If interested you could make your own batch. The 13 supplements are in the second photo.
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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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Neo
#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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nikari
#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
2 Likes
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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AnUser
#623
It might upregulate PCSK9 among other things for some, which is anti-longevity.
Bryan is a Hero.
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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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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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.
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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jnorm
#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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AnUser
#629
Please do better, he did say his glucose dropped, high cholesterol was corrected, and soft tissue infections went away.
1 Like
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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jnorm
#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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AnUser
#632
Whether it didn’t increase his aging speed is besides the point, what matters is longevity and worsening of cholesterol, glucose, soft tissue infections, and RHR is not good for longevity. This should be obvious, and there’s nothing to suggest rapamycin will offset that.
I’d say to look at the marmoset, mouse, and the other 70+ Rapamycin studies that show positive longevity results vs. one Bryan Johnson who is using a flawed epigenetic test. The marmoset’s epigenetic ages worsened, but they lived a heck of a lot longer and healthier anyway! Epigenetic age tests are inherently flawed.
You can also have a low ApoB/LDL and take Rapamycin at the same time. I found that Bempedoic Acid, Ezetemibe, and a low-dose statin more than compensate for any Rapamycin bumps in lipids.
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Paul
#634
my dose on a per lb basis is 50% higher than his and my RHR has never been lower (45)
2 Likes
AnUser
#635
I shouldn’t repeat what I already said, so here’s the response to exactly this, unless you believe this counters anything I said: