While I believe aging is inevitable, as is death, I do also believe that humans have genetic predispositions to longer life, or not. My 98 year old mother has severe dementia but is remarkably sound in body, still. And she never exercised, nor did she eat well. Her mother and sister, the same. But they all (as do I) seem to conform to what I think of as a “catabolic” or slow growth phenotype. And I may be wrong about this, but I think that the main mode by which rapamycin may extend life is by pushing away from the growth or anabolic toward the slowed growth catabolic. Since I am naturally positioned on the catabolic end of the spectrum, I decided not to take rapa. But I do try to behave well along all the dimensions, diet, sleep, exercise, BMI/calorie restriction, etc,
I often find the long term trends helpful for my personal optimism. World in Data is my go to 
But… don’t you think you could prevent dementia or alzheimer’s potentially using rapamycin. As you see it in your mom.
Matt Kaeberlein says using rapamycin before onslaught can prevent dementia and many cancers.
Could Rapamycin prevent or delay Alzheimers? I would feel more persuaded if I could understand the mechanism of action – how does it prevent…? For example, I take Raloxifene, which is a selective estrogen reuptake modulator (“SERM”). It works by lodging in the estrogen receptors in the breast, thereby preventing estrogen from stimulating the breast cells. Since I had a very tiny, very indolent estrogen driven cancer, taking raloxifene makes sense – I understand how and why it is appropriate for me. It is also low risk and helps with bone remodeling. Similarly, snorting insulin seems to make sense for me personally since I have very low endogenous insulin, and research has shown that intranasal insulin can help the brain utilize glucose and can be neuro protective. So I understand why it might be protective and a good idea for me personally. And it is low risk.
I would love to understand how rapamycin might protect against Alzheimers. What is the mechanism? I think that if my major worries were cancer, a disease of overgrowth, I would take it. But Alzheimers – is sometimes called “type 3 diabetes”. And rapamycin can raise blood glucose. And I naturally have pre-diabetes level glucose.
I would really welcome inputs, vewpoints on this. Argue with me.
You might want to research Dr. Ai-Ling Lin’s work on human clinical trials and rapamycin with the hippcampus benefits for those wqith APOE-4 genetic predespositoin for Azheimers.
Was earth shattering for those working with neurological issues like Alzheimers.
Ai-Ling Lin, PhD. - Vice Chair for Research, Radiology
Professor, Radiology and Biological Sciences
Professor, Institute for Data Science & Informatics
Roy Blunt NextGen Precision Health Building
University of Missouri
1030 Hitt Street
Columbia, MO 65212
Lab website: https://linbrain.com/
Thanks for this. It does describe fairly convincingly how rapamycin might improve brain functioning – if you are APOE4. But says that these benefits are not necessarily there if you are not APOE4. I am APOE3/3.
I couldn’t comment on rapamycin’s effect on Alzheimer’s (as i obviously don’t have Alzheimer’s) but I used to forget a lot. I did Rapa for about a year (and many other supplements) and nothing seemed to help with my memory. I would literally at times forget names of people I’ve been working with for last seven year LOL.i.e instead of asking the receptionist tell Bianca to come to my office I’d say tell the girl next to you come to my office. They would think I was doing it to be funny (lol) but it was literally that bad some days, some days It was better. Fast forward to couple months ago when I started taurine and my memory is so brisk that I can’t even believe it myself. Since Alzheimer’s has some of the same symptoms, I’d have to think that taurine must be on every person’s list who is concerned about memory loss, dementia, and maybe even Alzheimer’s. Again, this is n-1 but the effects were so significant that I had to mention it.
Alzheimer’s disease and the therapeutic effect of taurine
The neuroprotective effects of taurine have been shown to protect against various forms of dementia. Beresewicz-Haller et al. (2023) investigated the ability of taurine to improve cognition in a transgenic mouse model of AD. They administered taurine orally through drinking water to amyloid precursor protein (APP)/PS1 transgenic mice for six weeks. The results of the experiment showed that taurine treatment can improve the cognitive performance of the APP/PS1 mice without affecting their behavior in the Y-maze or passive avoidance test (Chen et al., 2019). In a transgenic AD mouse model, it has been shown that taurine has the ability to improve cognitive abilities. The insoluble fraction of amyloid beta (Aβ) in the cortex of APP/PS1 mice decreased when taurine was added, suggesting that it may help reduce cognitive impairment and Aβ-induced damage, as shown in Additional Table 1 (Kim et al., 2014). Taurine has been shown to block the neurotoxic effects of Aβ on rat hippocampal and cortical neurons in culture. Taurine supplementation may also protect central neurons from excitotoxicity caused by high concentrations of glutamate extracellularly. The neuroprotective effects of taurine are abolished by picrotoxin, an antagonist of GABA-A receptors. Neuronal death caused by Aβ in rat hippocampal and cortical areas can be prevented by GABA and muscimol, an agonist of the GABA-A receptor (Fontana et al., 2020). The use of taurine in the treatment of AD may be beneficial because of its ability to modulate GABA-A receptors and protect neurons from Aβ toxicity in AD-affected regions of the mammalian brain and from excitotoxicity (Paula-Lima et al., 2005). Taurine shows a beneficial role in AD by improving cognitive function in oligomeric Aβ mice. It restores acetylcholinesterase and acetylcholine transferase activities and inactivates microglia-dependent neuroinflammation to bypass dopaminergic neurons (Fontana et al., 2020).
Found this as I was researching indolepropionamide
Indoles as essential mediators in the gut-brain axis. Their role in Alzheimer’s disease
https://www.sciencedirect.com/science/article/pii/S0969996121001522?via%3Dihub
One of these indoles – IAA or indole-3-acetic acid / acetate – is the villain in this Nick Norwitz video (the hero is AKG):
I hope this guy isn’t just saying this to sell supplements with his affiliate link.
Not all indole molecules would be the same.
He is demonizing something shown to increase lifespan in fruit flies so we need more data instead of just dismissing it.
AKG does seem to be a healthy supplement however. I take AAKG, funnily enough I take it BECAUSE I want to increase indole production in the gut and this acts upstream from that.
Since an early age I witnessed family members and relatives with physical and mental ailments that made their lives difficult. Around the year 2000 after my father’s death I decided I would prefer to avoid those problems if possible. I wondered, “Would that be possible?” So, I started my first medical research around heart attacks and strokes. My goal has been and continues to be to maintain a physically fit and mentally capable body as long as possible with as short a period as possible for rapid decline and death. I want to enjoy the “golden years,” not suffer through them. If I can maintain health during my later years it may result in a longer life, but that is not the goal. And, “immortality?” No. That’s not going to happen!
That’s interesting. Started taking Ca-AKG about a year ago for other reasons.
1gm per day. Fortunately it’s quite inexpensive, if you know a guy
Didn’t have an impact in the ITP btw.
That’s true. Fish oil also didn’t pan out, though may have increased healthspan of mice.
Then there’s aspirin to consider. In a 2004 ITP study a dose of 20 ppm saw a median male mouse life-extension (p=0.01); but with later doses in 2014 at 60 ppm and 200 ppm there was no effect. AKG could be similar to that.
Glad I’m not a mouse
Therefore, results from animal models, including the popular murine ones, are not always translatable to humans and conclusions should be made with caution. In addition, even well-controlled gut microbiota experiments using mouse models show important inter-study variations due to confounding factors in the experimental setup, such as mouse house origin, maternal effects, environmental conditions (food composition, light, stress factors, pathogen infection), genetic backgrounds and in the downstream analysis methods applied
My argument is that if it doesn’t even help those little cancer factories in a lab and positive studies in humans are non-existent (the study by Professor Kennedy got shelved), how can we expect to get any benefit from it? The supplement is way too expensive to be justified.
Depends on the source
AKG does seem to do something in drosophilia and mice, whether it’s helpful in humans I agree that the evidence is weak but it does seem to have an effect on our favorite surrogates
https://www.sciencedirect.com/science/article/abs/pii/S156816372030372X
https://www.sciencedirect.com/science/article/abs/pii/S0306456516300195
https://www.sciencedirect.com/science/article/pii/S1550413120304174
the study by Professor Kennedy got shelved
If you’re talking about the study at Indiana University, if that one has been “shelved”, it’s likely not due to Kennedy but Ponce de Leon Health who funded the study (I think).
I would guess a scientist like Kennedy would want to publish a negative result of this sort. The only reason that I can see for him not to want to publish would be if there were gross errors in running the experiment. Kennedy has grad students and postdocs that need papers published, and even a negative result would help satisfy that need. (Also, it’s my understanding that in that experiment they discovered, post hoc, that the test subjects had unusually low epigenetic age, and were extra-healthy; so AKG had less of an effect than they were hoping to see, but Kennedy has said that within the group of people with average or above-average epigenetic age, they found AKG lowered their epigenetic age substantially).
I believe there is another study that is finishing up at the National University of Singapore, funded by the Singapore government.
My guess would be that both studies will be published eventually. It just takes time to write it all up. By comparison: as I recall, the big taurine study that came out a few years ago (on its deficiency being a driver of aging) took many years to complete. I had remembered it took 10 years, in fact, but couldn’t find any references for this (my memory could be in error). It might have been mentioned in an interview with some of the study authors.
They could have released the study for anyone to analyze the subgroups.
My understanding is that if something actually lowers your epigenetic age (which is still vodoo science atm) it should delay cancer formation which has not been seen in mice trials.
I asked this question to OpenAI’s o3 model:
Is it customary for university biomedical researchers to share research data before even issuing a preprint about the work, and if not then why not?
The short answer is:
No —outside of a few high-profile consortia and public-health emergencies, most university biomedical groups do not make their raw research data public before they have at least posted a preprint (and usually not until the accompanying paper is accepted or published). Funders and journals encourage openness, but their formal policies generally set the deadline for data release at or just after manuscript acceptance, so there is little structural incentive—and several disincentives—to post datasets earlier.