Rapamycin: Anti-aging and metabolic dream drug?
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Rapamycin is anti-MUFA and anti-cancer.
I suspect that a significant part of rapamycins anti aging effects are similar to having a low PUFA intake. Since rapamycin mostly works through lowering excessive inflammation, which is largely caused by PUFA consumption.
In this in vitro study the authors showed a that rapamycin inhibited SCD1 via mTOR inhibition, which lead to a decrease in breast cancer size.
"In all three cell lines, we found that rapamycin significantly decreased polysome-associated mRNA for stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzyme in monounsaturated fatty acid synthesis. Activators of mTOR increased SCD1 protein expression, while rapamycin, LY294002 and BEZ235 decreased SCD1 protein expression. "
Also, simply increasing MUFA via SCD1 was enough to cause breast cancer growth, while lowering MUFA had the opposite effect.
"Furthermore, SCD1 siRNA knockdown inhibited breast cancer cell growth, while over-expression increased growth. "
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965451/This is only in vitro, so take it with a grain of salt. But I think it coherently outlines a logical mechanism of action . Plus: in several other studies SCD1 has been down to be pro-cancer (and other diseases) and rapamycin has been shown to be anti-cancer. Btw this is "only" increasing MUFA and it already has such terrible effect on the organism, now imagine what increasing PUFA would do...
https://www.cell.com/trends/cancer/fulltext/S2405-8033(23)00032-8 -
Btw today was my first day taking rapamycin myself.
I started with 1mg.
And I notice that I feel very energetic. Normally I feel quite tired after a day of work but today I feel fit, especially mentally. Less brainfog. Also my mood is better.I also notice that I'm calmer and more patient with people.
It's all very early but so far so good.
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Day 2:
Slept really well. Better than usually . Lost 500g of body weight. Last evening I noticed my metabolism increasing and me heating up.Today I Had a great, day . Felt engaged and interested in what I did . Maybe a little tired ,but nothing crazy.
I had some gut "detoxes" today. Less hair loss.
Motivation increased. Strength was about the same. -
Day 8:
Last days felt hypothyroid, gained water weight.
Had rapamycin yesterday and today lost water weight. Weigh 650g less than yesterday morning, although I ate more than the days before.
Took rapamycin before work... Not a good idea. Was stressed and tired. Will return to after work.I suspect that there might be a rebound mTOR effect after a few days of no rapa, hence the hypothyroid symptoms .
Or Maybe that's the "physiological insulin resistance" that is transient and materializes itself at the beginning of rapamycin treatment.
IIRC rapamycin caused water retention for tarmander as well but it went away.Other than that my energy might be slightly higher but not sure yet.
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With rapamycin, I’ve always wondered how many effects are downstream of its anti fungal and anti biotic effects. Is there any studies with it in germ free animals?
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@jamsey found this, but not much else:
https://www.nature.com/articles/s41598-019-44106-5 -
@jamsey Hey, I wonder if this is the wonder drug to get bacterial infection in lymph nodes and bone???
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Rapamycin increases klotho.
It is even more Peaty than I thought because it lowers phosphate. And phosphate activates mTOR. Rapamycin lowers phosphate and mTOR, decreasing calcification.
"Zhao et al. report that phosphate activates the mammalian target of rapamycin (mTOR) cascade in VSMCs, leading to downregulation of Klotho. Furthermore, rapamycin was shown to halt medial calcification. This effect was blunted in the absence of Klotho. Given the concomitant anti-atherosclerotic effects of the mTOR inhibitor, this agent has clinical potential as an inhibitor of intimal atherosclerosis and medial calcification."
https://pubmed.ncbi.nlm.nih.gov/26422620/
Here, it also increases klotho in aging mice. And it caused a huge increase in survival.
"All mice administered rapamycin survived the 12-week course, whereas 43% of the controls died."
https://pubmed.ncbi.nlm.nih.gov/37190667/
It decreased phosphate in humans.
"In the rapamycin group, serum phosphate was lower than in the CNI group with an increase in phosphate excretion and a reduction in its reabsorption."
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I will tag you, but this question can be addressed to anyone here who is taking this “Wonder drug“
How do you reconcile that this is big Pharma:
Pfizer and Wyeth?Red flags personally for me as well as it’s catching on mainstream
Of course I think it has therapeutic benefits, but I would isolate those to compromised kidney patients, etc.
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Rapamycin might help schizophrenia by lowering mTOR.
Schizophrenics have increased 5ht6 activation which in turn activates mTOR.
"Further, 5-HT(6) receptor activation increased mTOR signalling in rodent prefrontal cortex (PFC). Linking this signalling event to cognitive impairment, the mTOR inhibitor rapamycin prevented deficits in social cognition and novel object discrimination induced by 5-HT(6) agonists. In two developmental models of schizophrenia, specifically neonatal phencyclidine treatment and post-weaning isolation rearing, the activity of mTOR was enhanced in the PFC, and rapamycin, like 5-HT(6) antagonists, reversed these cognitive deficits. These observations suggest that recruitment of mTOR by prefrontal 5-HT(6) receptors contributes to the perturbed cognition in schizophrenia, offering new vistas for its therapeutic control."
https://pubmed.ncbi.nlm.nih.gov/23027611/ -
Rapamycin, fisetin and other anti-aging compounds (but not Metformin) help with stem cell formation .
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Another macrolide antibiotic Azithromycin also inhibits mTOR according to these studies:
https://pubmed.ncbi.nlm.nih.gov/34600916/
https://pubmed.ncbi.nlm.nih.gov/37633240/
https://pubmed.ncbi.nlm.nih.gov/30334401/Although there is one study that said it didn't have an effect on mTOR:
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Azithromycin might have interesting anti-aging effects. It targets senescent cells very effectively and without targeting healthy cells. The effect is concentration dependant though .
"Azithromycin preferentially targets senescent cells, removing approximately 97% of them with great efficiency. This represents a near 25-fold reduction in senescent cells."
"Azithromycin, at 100 μM, had no effect on the viability of normal MRC-5 lung fibroblasts, but selectively killed only senescent MCR-5 fibroblasts."
"Neither drug showed any significant effects on viability at 50 μM, indicating that the effects we observed were concentration-dependent."
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@Mauritio I took approx 40 mg azithromycin plus .5g of cypro daily for about 3 weeks during allergy season, and I seemed to do better than with just cypro.
I've wondered if there would be any negative effects from longterm lowdose usage, like Peat's concern that using too much of one antibiotic causing imbalance in the microbiome.
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@LetTheRedeemed interesting . Did you notice any other effects from it ?
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@Mauritio I couldn't connect if I was having digestive issues connected to it's prolonged use or not. there were a lot of confounders at the time. I'll probably try it again next time I use it with some penicillin traveling el snail mail.
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I’ve not been that impressed with rapamycin personally, as it gives me a headache and interferes with sleep.
But low dose naltrexone and deprenyl are quite amazing and are great longevity drugs. LDN in particular has made a huge different for so many people as it can seal leaky gut — which is the source of virtually all chronic disease as we age.
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@Ecstatic_Hamster say no more, where does one get LDN?
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@Ecstatic_Hamster I've been wanting to try LDN for a long time . Is there anywhere we can read about people's experience with it ?
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@Mauritio said in Rapamycin: Anti-aging and metabolic dream drug?:
Surprisingly this review argued that quinones would increase mTOR.
Because quinones increase Nrf2 which in turn increases mTOR.What should we think of that ?
In theory that would cause a pro-cancer effect, but quinones do lot more than activating Nrf2 ...Here's a few studies that a quinone, thymoquinine to be precise, inhibits mTOR and thus has an anti-cancer effect.
https://pubmed.ncbi.nlm.nih.gov/37288949https://pubmed.ncbi.nlm.nih.gov/37288949/https://pubmed.ncbi.nlm.nih.gov/30259603/
https://pubmed.ncbi.nlm.nih.gov/36145344/
