Intranasal Rapamycin Lessens Alzheimer-like Cognitive Decline in a Mouse Model of Down Syndrome

I shamelessly take and copy from
Blagosklonny’s paper “Rapamycin for longevity: opinion article”

“If you wait until you are ready, it is almost certainly too late.” ~Seth Godin

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A constant and accurate delivery method has been solved.

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Open Access Compounding

My compounding;
100mg of rapamycin powder
1ml of DMSO
99ml of IV saline solution at .9%

Curaplex Dart Nasal Atomization Device

1mg of rapamycin up each nostril.

I can hear the black in the dark room.

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My dosing mantra from Blagosklonny’s paper.
Have seen no reason to change.


ge.

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Yes for the periphery, simple indeed. The known side effects are liver, kidney, thymus, bone marrow, etc mediated.

Is the brain graph the same?

You stop oral Rapamycin, peripheral side effects dissipate. What if you continually slam your brain with mega doses, same “irreversible” benign response?

Without any attempt at translation of intranasal, we could be orders of magnitude off too low or too high…both bad. Too low, complete waste of time and money. Too high, well…uncharted territory.

Perhaps we will have intolerable immediate response. Not attempted to climb this mountain before.

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This seems good and further supports this approach…

Enhanced brain mitophagy slows systemic aging

Compromised clearance of dysfunctional mitochondria, through the process of mitophagy, has garnered attention as an essential contributor to aging and neurodegeneration. Schmid and colleagues1 reveal that genetic enhancement of mitophagy via neuronal overexpression of BNIP3 alleviates brain aging and prolongs healthspan in fruit flies.

In brief, mitophagy is a multistep process that is initiated through the engulfment of damaged or dysfunctional mitochondria by a phagophore, creating a mitophagosome. The mitophagosome fuses with an acidic lysosome, enabling degradation and intracellular recycling of the cargo. BNIP3 is a multifunctional protein that is localized to the outer membrane of the mitochondria, where it can act as either a proapoptotic protein or a mitophagy receptor. BNIP3 participates in the nucleation and elongation steps of mitophagy5 ensuring the recruitment of the phagophore to the mitochondrion by binding to the autophagosome protein, microtubule-associated proteins 1A/1B light chain 3B (Atg8A (known as LC3 in humans))6,7. Furthermore, BNIP3 binds to the central mitophagy protein PTEN-induced kinase 1 (Pink1), blocking its clearance and promoting mitophagy induction8.

Paper (Behind Paywall):

https://www.nature.com/articles/s43587-022-00226-8

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Anyone have a PDF copy of this paper?

I looked at the site and the “essential oils” part got me also. In my brain, not sure about that.

My plan for the most part is to follow Blagosklonny and Dr. Green and of course the fellow travelers on Rapamycin News and make adjustments as new information is available. As I said before, I am willing to take risks that I wouldn’t recommend to a younger person. And, those starting early will benefit from lower doses over time. For me the first side effect of too high of a dose is diarrhea. So far I haven’t had any lab reports that give me concern

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MAD Nasal™

STMAD300-nasal-MAD-5__22522.1593643726

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Huzzah!
(pdf of the whole article “Enhanced brain mitophagy slows systemic aging”)

Enhanced brain mitophagy slows systemic aging.pdf (941.8 KB)

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Hi - welcome to the forums. Thanks for posting and participating here.

Thats a really interesting paper I think…

Just a note - and we do this here accidentally all the time (accidental repostings), try to do a quick search on the site before you post new papers as it may have already been posted. Not a big deal since most people don’t read every post on the site, but it just helps keep the organization of the discussions focused on one thread vs. many threads so that its easier for people who come later to follow the conversations…

Here is my post the other week on this paper - with some related links to other papers too:

New here. Actually, I’m not sure that DMSO is needed. I believe that standard bacteriostatic saline is 0.9% NaCl and 0.9% benzyl alcohol, extremely safe and one of the few solvents that is stronger than DMSO on the list. You could just try mixing it directly and see if it dissolves.

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Hi Peter, and welcome to the forum. Do you have any experience with these compounds or nasal delivery mechanisms?

Given that we know rapamycin is a potent anti-inflammatory, this approach to delivery of rapamycin to the brain seems to have a lot of potential. A new study on this topic:

Neuroinflammation: A Possible Link Between Chronic Vascular Disorders and Neurodegenerative Diseases

Various age-related diseases involve systemic inflammation, i.e. a stereotyped series of acute immune system responses, and aging itself is commonly associated with low-grade inflammation or inflamm’aging. Neuroinflammation is defined as inflammation-like processes inside the central nervous system, which this review discusses as a possible link between cardiovascular disease-related chronic inflammation and neurodegenerative diseases.

Full Research Paper here:

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