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Topical Rapamycin Evaluated as a Treatment for Skin Aging


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#1 reason

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Posted 26 November 2019 - 11:22 AM


Given the attention that descends upon any prospect of reversing skin aging, I should probably open by saying that much of the data here for extended low dose topical treatment with rapamycin over eight months, that regarding visible skin aging and collagen production, is no more exciting than that obtained by any number of other approaches, such as topical application of keratinocyte growth factor (KGF). Effect sizes are the only thing that matters, and also the one thing that all too many observers fail to consider. Looking at the paper, I would say that the primary point of interest is the 50% reduction in markers of cellular senescence in skin. Given what is known of rapamycin this seems unlikely to be a senolytic effect, so not destruction of existing senescent cells, but rather a reduction in the number of cells becoming senescent. This in turn suggests that there remains some meaningful level of ongoing natural clearance of lingering senescent cells at older ages.

This study demonstrates a clear impact of rapamycin treatment on both the molecular signature associated with senescence and the clinical signs of aging in the skin. These data support the idea that a reduction in the burden of senescent cells underlies these improvements. The results could reflect a modification of the senescent cells present in the skin or a reduction in the number of senescent cells. Although rapamycin has been shown to reduce pro-inflammatory secretions produced by senescent cells, the fact that p16INK4A is reduced suggests that the absolute number of senescent cells in the epidermis is reduced. This implies that rather than simply modifying senescent cells present in the tissue, rapamycin treatment is either reducing the number of cells entering senescence or increasing the clearance of senescent cells. Based on our studies demonstrating that rapamycin prevents the senescence transition and improves functionality in vitro, we favor the concept that rapamycin reduces entry into senescence, but we cannot rule out an additional role for clearance of senescent cells. Whether the reduction in senescent cells is due to reduced entry or increased clearance, a reduction in the burden of senescent cells would be expected to improve functionality.

Senescent cells produce pro-inflammatory cytokines, matrix metalloproteins, and reduced levels of anti-angiogenic factors, creating a secretory profile known as the Senescence-Associated Secretory Phenotype (SASP). Thus, we anticipate that rapamycin treatment reduces inflammatory cytokines in the skin, although the verification of this change represents a technical challenge due to the fact that such cytokines are present in picomolar amounts. One quantifiable aspect of skin biology that is improved by the rapamycin treatment is the incorporation of collagen VII into the basement membrane, which represents a functional measure of skin quality that is improved upon treatment with rapamycin. Collagen VII is essential for a functional skin barrier, and the levels of collagen VII decrease with age and specifically beneath wrinkles. Although the mechanism whereby rapamycin may increase collagen VII protein levels is not clear at this time, the known effects of rapamycin on autophagy and intracellular trafficking of vesicles may allow for intracellular processing of misfolded collagen and increase proper localization at the cell periphery and basement membrane.

A notable aspect of this study is the use of such a low dose of rapamycin (10 μM, or 0.001%) for topical application. Topical treatment with higher concentrations (0.1-1%) has been employed for the treatment of tuberous sclerosis complex (TSC) in adults and children and has shown efficacy. We chose to use rapamycin at a ten-fold lower dose because the concentrations used in TSC patients are intended to inhibit cell growth, while our aim was to improve cell function while maintaining proliferative potential and preventing senescence. The positive impact of our treatment regimen suggests that age-related therapy with rapamycin may be feasible at doses far below those associated with side effects; however, this possibility will require careful evaluation in each specific clinical setting.

Link: https://doi.org/10.1...357-019-00113-y


View the full article at FightAging
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#2 adamh

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Posted 27 November 2019 - 01:07 AM

Yet another use for rapamycin. What would be interesting is a guide for home use. I just happen to have some rapamycin in powdered form and could easily make up a skin cream if I knew how to do it. I have it dissolved in alcohol right now at a fairly high concentration but could dilute it much more. Not sure if alcohol is good for the skin, I heard it was not. Perhaps mixing the concentrate with an oil such as coconut or jojoba, etc would work?

 

I also don't know how to make a molar solution. I need x number of mg per gram or liter to proceed. Can anyone shed some light on this? The article says nothing about making the cream or serum



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#3 male_1978

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Posted 27 November 2019 - 07:56 PM



Yet another use for rapamycin. What would be interesting is a guide for home use. I just happen to have some rapamycin in powdered form and could easily make up a skin cream if I knew how to do it. I have it dissolved in alcohol right now at a fairly high concentration but could dilute it much more. Not sure if alcohol is good for the skin, I heard it was not. Perhaps mixing the concentrate with an oil such as coconut or jojoba, etc would work?

 

I also don't know how to make a molar solution. I need x number of mg per gram or liter to proceed. Can anyone shed some light on this? The article says nothing about making the cream or serum

 

 

From the study:

 

 

 A notable aspect of this study is the use of such a low dose of rapamycin (10 μM, or 0.001%) for topical application.

 

 

0.001% is a ratio of 1 : 100.000.

 

If you have tablets with 1 mg you would have to disolve it in 1 mg* 100.000 = 100 g of your solution, which would be 0,1 liter if it was water.

 


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#4 male_1978

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Posted 27 November 2019 - 08:08 PM

In german: 

 

This describes how to make a topical cream with rapamycin:

https://www.deutsche...ts-angiofibrome

 

 

 


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#5 adamh

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Posted 27 November 2019 - 10:18 PM

That is an interesting article but making a solution with vasoline might be difficult. The grinding and mixing part is what I'm thinking about. I'm not sure if ethanol will mix with vasoline or not. If it does I could go from my solution to the vasoline and mix something up. Its worth a look. I keep my rapamycin in the freezer so it should last a long time

 



#6 Phoebus

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Posted 28 November 2019 - 04:44 AM

That is an interesting article but making a solution with vasoline might be difficult. The grinding and mixing part is what I'm thinking about. I'm not sure if ethanol will mix with vasoline or not. If it does I could go from my solution to the vasoline and mix something up. Its worth a look. I keep my rapamycin in the freezer so it should last a long time

 

 is it water soluble? 

 

If so no need for grinding, just leave it soak for a good while eventually it will dissolve. 



#7 adamh

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Posted 30 November 2019 - 02:41 AM

 is it water soluble? 

 

If so no need for grinding, just leave it soak for a good while eventually it will dissolve. 

 

No its not water soluble, but will dissolve in alcohol and I think ethylene glycol. I have mine in alcohol I'm just not sure if it will mix with the vasoline or not. If not then I will have to get some e glycol and try that

 

male_1978 all we have to do is click translate and it goes into english. I think the article said .001% but they also used .01% and it worked the same. No point in making a solution too strong


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#8 michael0505

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Posted 30 November 2019 - 11:38 AM

While you're at it and if one has this issue, perhaps try a spot where gray hair is present, see if there is any reversal?


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#9 Phoebus

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Posted 01 December 2019 - 03:12 AM

While you're at it and if one has this issue, perhaps try a spot where gray hair is present, see if there is any reversal?

 

 

Is there any reason so suspect it might reverse gray hair? 



#10 Kentavr

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Posted 01 December 2019 - 06:42 AM

In one blog (not this forum), one person shared his research. He used NMN and spermidine. His hair and beard were turning dark again.

Spermidine, like rapamycin, enhances autophagy. Perhaps this is a good replacement for rapamycin in this.
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#11 OP2040

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Posted 02 December 2019 - 04:43 PM

With such a small dose, this would be a great and cost effective use of Rapamycin.  I can see why Vaseline wouldn't work, it's built to prevent things from entering the skin, exactly the opposite of what we want. 

 

Why not just use whatever lotion is lying around?  There was that study a while back showing that some anti-aging lotion, mainly a bunch of oils like in most lotions, did get into the skin and profoundly reduced cytokine production when applied to just he skin.  Using something similar to the lotion from that study would kill two birds with one stone, ya think?

 

From the study, the topical lotion was something called Atopalm(®) Multi-Lamellar Emulsion Cream and Physiogel intensive ccream.  That's a mouthful!  And from the Atopalm website, the $25 Atopalm Intensive Cream ($21 on amazon).  Fairly cheap considering how little you would need to use for this experiement.  But for those that want to know more or DIY, ingredients:

 

 

Water/Aqua, Glycerin, Propanediol, Myristoyl/palmitoyl Oxostearamide/arachamide MEA, Caprylic/capric Triglyceride, Cetearyl Alcohol, Glyceryl Stearate, Polyglyceryl-10 Distearate, Vitis Vinifera (grape) Seed Oil, Sorbitan Stearate, Portulaca Oleracea Extract, Dimethicone, Hydrogenated Vegetable Oil, Olea Europaea (olive) Fruit Oil, Tocopheryl Acetate, Simmondsia Chinensis (Jojoba) Seed Oil, Sodium Hyaluronate, Phytosterols, Carbomer, Caprylyl Glycol, 1,2-Hexanediol, Arginine, Stearic Acid, Allantoin, Fragrance, Tropolone

      

Hydrogenated vegetable oil is kind of ironic here, considering how much people try to avoid eating it.  Also, is that not Vitamin E acetate I spin there as well.  Please nobody smoke this stuff!

 

Anyway, do we have consensus for the above calculations, basically 1mgRapa/100Gsolution.  Won't this be way too much?  Would lotion change this ratio at all? 

 


Edited by OP2040, 02 December 2019 - 04:53 PM.

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#12 Engadin

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Posted 02 December 2019 - 06:47 PM

Here another procedure for making a rapamycin topical cream, this time in english: Formulation and characterization of a 0.1% rapamycin cream

 

 

 

 

.

 

 

Sorry I posted a wrong link above. This is the right one: https://www.sefh.es/...in0.1_cream.pdf

 

Attached File  Crema Rapamicina.jpg   14.64KB   0 downloads
 
Transcutol (an excellent permeation agent that enhances drug diffusion through the skin) is not too expensive (around 15$/250 grs.) and the Excipial Hydrocrème (10$/50 ml.) either. This formulation is for a 0,1% compound while we need a 0,001% mix. The most direct way to convert the table above to our needs of a 0,001% mix is to divide the amount of rapamycin by 100 to transform the 0,1% into a 0,001% mix. In other words 0,03 grs. of rapamycin would turn into 0,3 mg. The critical point is how to measure such a minimal amount. And the only way is to get an expensive digital scale.
 
To overcome the scale drama another option to get a 0,001% formulation is 3 mg. of rapamycin in 15 grs. of Transcutol (at a cost of less than one dollar) and 300 grs. of Excipial Hydrocrème (at a cost of 60$). That makes a total of 61$ to add to Rapamycin 3 mg. costs (from 40$ and above, depending on provider).

Adapting each component's amount to the displayed in the previous paragraph, the way to prepare the cream is as explained in the link above:
"The cream was prepared by first solubilizing rapamycin in Transcutol. This mixture was then progressively added to Excipial Hydrocrème under manual stirring for several minutes. The formulation is presented in Table 2 (the table above). The rapamycin dosage in the cream was 0.1% (w/w), which is in the low range of the previously published formulations but here the active drug was solubilized and a much higher level of activity was therefore expected. As explained above, the high level of solubility of rapamycin in Transcutol would allow a dosage of 0.4% if needed without affecting the appearance of the cream or physical stability. Because of rapamycin toxicity, preparation was performed in a low pressurized glove-box to protect the pharmacy technician. Excipial Hydrocrème was selected from various commercially available formulations as it is an oil-in-water emulsion composed of safe ingredients, is non-comedogenic and not unpleasant to use. The final cream has a slight oil odour, a homogeneous appearance and is white in colour. These characteristics remained constant throughout the study."
 

 

 
 
.

Edited by Engadin, 02 December 2019 - 07:32 PM.

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#13 adamh

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Posted 02 December 2019 - 08:40 PM

I would think the best way to do it is to dissolve some rapamycin in a solven then add that to the cream. Why do I say that? Because as has been said, it takes a very expensive scale to measure such tiny amounts also takes training to use the scale. Using a cheap mg scale you can measure an amount like 20mg fairly accurately while 0.3 or 0.03 would be impossible. 

 

You put the large amount in a known volume of solvent and then you have x mg per milliliter of solution. This is very easy to measure, you can measure out .001 mg if you like which might be .1 ml.

 

Alcohol will work but will it mix with the cream? If it would mix with coconut oil, for example, then it would be easy to make a lotion to put on the skin. Ethylene glycol works too, that might mix with an oil more easily or put it in with one of those skin creams mentioned. 

 

If you have r in tablet form, its also very easy. With a 5 mg tab, take 1/4 weigh it and you can get tiny amounts. If the 1/4 tab weighs 50 mg then 5 mg = 1.25/10 = 0.125. Most decent mg digital scales will measure that amount accurately. Or if you want even less, just eyeball the tab and scrape off a tiny bit. Errors of 100 to 200% are not important. One study was .001% and another was .1% and they both seemed to have good results

 

I'm going to search and see if alcohol will mix readily with a cream. I doubt it will mix with coconut oil but that would be the easiest way to do it if they are miscible. My solution is 5 mg per ml so a tiny drop would be about .1 mg.

 


Edited by adamh, 02 December 2019 - 08:45 PM.


#14 adamh

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Posted 02 December 2019 - 09:51 PM

On second thought, dmso might be a better solvent than the others. Rapamycin will dissolve in it though from what I read it might help to warm the dmso and leave it sit overnight to make sure its all dissolved. It would have the further benefit of being able to penetrate the skin while vasoline does not. DMSO should also mix well with many other things

 

But if the study with vasoline worked, then most any vehicle should work as long as the rapamycin can dissolve in it or the solvent you use can mix evenly with the carrier. I plan to test mix and make up a cream in the near future



#15 aribadabar

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Posted 12 December 2019 - 12:36 AM

Ditmethyl isosorbide (DMI) is another widely available excellent solvent for R


Edited by aribadabar, 12 December 2019 - 12:42 AM.


#16 QuestforLife

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Posted 12 December 2019 - 10:24 AM

I had a go at making this. I used one 1mg rapamycin pill in 100g of Atopalm. I only had about 90g of atopalm left after my (mis)adventures making another cream, but probably lost a little rapamycin in the process, so think the concentration is about right. After crushing and sieving the pill it felt a lot like homeopathy. Will this really do anything? Looking at the paper the results are interesting without being mind blowing and they used the cream for 6-8 months. One other note for those using crushed tablets. They also contain filler lactose monohydrate , sucrose etc. in greater quantities than the rapamycin.


Edited by QuestforLife, 12 December 2019 - 10:25 AM.


#17 male_1978

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Posted 13 December 2019 - 09:24 AM

I had a go at making this. I used one 1mg rapamycin pill in 100g of Atopalm. I only had about 90g of atopalm left after my (mis)adventures making another cream, but probably lost a little rapamycin in the process, so think the concentration is about right. After crushing and sieving the pill it felt a lot like homeopathy. Will this really do anything? Looking at the paper the results are interesting without being mind blowing and they used the cream for 6-8 months. One other note for those using crushed tablets. They also contain filler lactose monohydrate , sucrose etc. in greater quantities than the rapamycin.

 

Are you documenting it with some before and after pictures? 



#18 QuestforLife

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Posted 13 December 2019 - 01:57 PM

Are you documenting it with some before and after pictures? 

 

I'm trialling something else right now, but rest assured when I start I'll take photos. I think I'll probably do the hands as that is easier than the face to spot changes. Because its such a low concentration of rapamycin and I have plenty in the cupboard, I'll probably just mix in a crushed tablet every time I buy another tub of Atopalm (~100g) and use it to keep my hands moisturised throughout the winter months.


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#19 adamh

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Posted 13 December 2019 - 10:45 PM

I too am trying it. I bought some propylene glycol since rapamycin dissolves in it and its non toxic. Its also miscible with water and alcohol. The rap will not dissolve in water but I have it already in alcohol. I put 250 mg into 50 ml and can easily measure out what I need. I think the powder I got is genuine but maybe a little weak. I had to up the dose a bit and then it acted like the pills did.

 

So I put 3 drops which was roughly perhaps 0.1 to 0.2 mg into an oz of the p glycol giving a solution of around 0.04%. I have been using it for several days but I don't expect any results soon. Perhaps in a month or two

 


Edited by adamh, 13 December 2019 - 10:46 PM.

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#20 sub7

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Posted 05 January 2020 - 02:09 PM

I had a go at making this. I used one 1mg rapamycin pill in 100g of Atopalm. I only had about 90g of atopalm left after my (mis)adventures making another cream, but probably lost a little rapamycin in the process, so think the concentration is about right. After crushing and sieving the pill it felt a lot like homeopathy. Will this really do anything? Looking at the paper the results are interesting without being mind blowing and they used the cream for 6-8 months. One other note for those using crushed tablets. They also contain filler lactose monohydrate , sucrose etc. in greater quantities than the rapamycin.

 

Thanks a ton for this info

 

Isn't the greatest challenge here obtaining a homogeneous mixture?

How would you go about making sure that each ml of the cream contains roughly the same amount of the active ingredient?

 

Also, ,f one has liquid Rapa on hand, what would be the best strategy to make a cream out of it in your opinion?

 

Thanks a lot



#21 ortcloud

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Posted 08 June 2020 - 08:11 PM

I too am trying it. I bought some propylene glycol since rapamycin dissolves in it and its non toxic. Its also miscible with water and alcohol. The rap will not dissolve in water but I have it already in alcohol. I put 250 mg into 50 ml and can easily measure out what I need. I think the powder I got is genuine but maybe a little weak. I had to up the dose a bit and then it acted like the pills did.

 

So I put 3 drops which was roughly perhaps 0.1 to 0.2 mg into an oz of the p glycol giving a solution of around 0.04%. I have been using it for several days but I don't expect any results soon. Perhaps in a month or two

 

Are you applying to your hands or hand as an experiment or are you applying to your face?

 

Any updates or results?

 


Edited by ortcloud, 08 June 2020 - 08:12 PM.


#22 adamh

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Posted 08 June 2020 - 11:45 PM

I haven't really followed up on that. Had too much going on






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