Rapamycin May Slow Skin Aging (Drexel U. Study)


(image source: here)

I’m pulling this old topic out to its own thread since there seems to be some significant interest in it, and it was previously buried in the general “Rapamycin for Hair Growth and Repigmentation” thread.

In the current Drexel-led study, 13 participants over age 40 applied rapamycin cream every 1-2 days to one hand and a placebo to the other hand for eight months. The researchers checked on subjects after two, four, six and eight months, including conducting a blood test and a biopsy at the six- or eight-month mark.

After eight months, the majority of the rapamycin hands showed increases in collagen protein, and statistically significant lower levels of p16 protein, a key marker of skin cell aging. Skin that has lower levels of p16 has fewer senescent cells, which are associated with skin wrinkles. Beyond cosmetic effects, higher levels of p16 can lead to dermal atrophy, a common condition in seniors, which is associated with fragile skin that tears easily, slow healing after cuts and increased risk of infection or complications after an injury.

If you have any friends who are chemists / biologists and have access to reagent suppliers, you can order rapamycin powder from suppliers like LC Laboratories. I’ve heard that some people crush up their sirolimus tablets to make rapamycin cream. See instructions here: DIY Rapamycin Cream.

Lower purity rapamycin powder (e.g. from China) may also work in this application and be ok because the rapamycin skin study showed that topically applied rapamycin does not get into the blood stream, so you don’t have to worry about contaminants in lower quality rapamycin powder getting into your body.

Here is the best paper I’ve found that has detailed instructions on making a topical rapamycin cream. I imagine we could just use the Transcutol and rapamycin (mixed with a blender) in a formulation with a dropper to put it on the scalp for the “hair tonic” approach.

For topical / serum applications I used Transcutol to dissolve the rapamycin in. [I tried rapamycin cream for skin for 6 months, it works to reduce fine wrinkles but it wasn’t a huge benefit and new research came out later (see bottom of this post) that suggests that it may do some negative things to the skin also].

Note: Transcutol has a number of different chemical names/identifiers. Here is a list: 2-(2-Ethoxyethoxy)ethanol: 3,6-dioxa-1-octanol, DEGEE, diethylene glycol monoethyl ether, Carbitol, Carbitol Cellosolve, Transcutol, Dioxitol, Polysolv DE, Dowanal DE

Transcutol Chemical Identifier: CAS Number 111-90-0

Where you can order Transcutol from:
LotionCrafters: Transcutol / Ethoxydiglycol
Laballey.com: Transcutol / Diethylene Glycol Monoethyl Ether

The mTOR/Rapamycin/Hair research was previously identified by Matt Kaeberlein and Peter Attia:

See this thread for more information on Rapamycin for Hair Growth and Repigmentation.

But there is also research that suggests rapamycin may not be that good for the skin, increasing inflammatory markers (which is not a good sign), and triggering a breakdown of the extracellular matrix:

"Rapamycin is a long studied molecule affecting mTOR/nutrient signaling and has recently been shown to decrease P16 levels of aging skin21, therefore it was chosen as a positive control of senotherapeutic effect in aging skin models. " … “Rapamycin induced a significant increase in P16 expression, a trend towards increased expression of inflammatory markers (IL6 and IL8), and a significant decrease in Keratin 1 gene expression levels (Fig. 3B). In the dermis, peptide 14 treatment promoted a significant reduction in B2M gene expression, a pro-aging factor, as well as in the expression ofIL8. Rapamycin treatment induced no significant changes in these markers and increased Matrix Metalloproteinase-1 (MMP1) gene expression, indicative of breakdown of the extracellular matrix (Fig. 3C).”

Source:

Senotherapeutic peptide reduces skin biological age and improves skin health markers

https://www.biorxiv.org/…/10.1101/2020.10.30.362822v2.full

More Rapamycin for Aging Skin reading:

It appears that a company has been formed that is working at commercializing this type of treatment for skin aging. For more information see Bionca Therapeutics: https://www.boincatx.com/

Related Reading: Senolytics Topically Administered to Skin for Antiaging Effects

Oral Rapamycin and Skin Aging

We have also had some good reports on skin health from people that even just oral rapamycin (which most of the people on this forum take via sirolimus tablets. Additionally, I believe there is significant evidence that rapamycin prevents a great deal of facial / skin aging more broadly defined (the changes in an aging face include loss of muscle tone in the face, fat distribution changes, etc.) and there is evidence that rapamycin slows many of these types of changes; for example rapamycin has been shown to slow muscle aging: Even with Calorie Restriction, Rapamycin Slows Muscle Aging. Studies have also shown that oral rapamycin slows the aging of most organs of the body, and our skin is the largest organ of our body, so it seems a reasonable bet that rapamycin will also have a significant impact in terms of slowing skin aging and the sagging of facial features that is common in aging humans.

Here is an example of one of our forum members here describing his experience with oral rapamycin helping with aging skin (from this post in our discussion forums):

I had suffered chronic actinic keratoses for decades because of my extreme exposure to sunlight when I was young. We did not have the benefit of the high SPF suntan lotions that are now available.
Rapamycin taken internally has had a truly remarkable effect on my skin. Actinic keratoses are precursors to cancer and are cancerous in nature. I saw my dermatologist 3 to 4 times a year. I have not seen a dermatologist since I started taking rapamycin.
Here are the before and after photos. The first one is not as bad as it looks. It just is the way it looks after typical “Blue Light” therapy.

actinic keratoses

Original Research Paper:

RapamycinAgingSkins11357-019-00113-y.pdf (4.3 MB)

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For two months, I’ve been using Dr. Green’s recipe, and I’ve noticed a slight darkening and very slight thickening of the hair at the hairline. No noticeable change to my skin. Since I’ve also been taking rapa orally during that same time, it’s impossible to know if it’s the cream. On his website, search the homepage for “The direction are add 1 capsule, 3 mg sirolimus, to 3.5 0z of Aquaphor Ointment. 3.5 Oz”

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Are you rubbing this on your head as well as your skin?

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Details from Dr. Green’s website:

The direction are add 1 capsule, 3 mg sirolimus, to 3.5 0z of Aquaphor Ointment. 3.5 Oz is 99 gm or 99,000 mg. When add 3 mg to jar of 99,000 mg preparation is .003%. I use a much stronger preparation (15 capsules in 3.5 Oz to make a 0.045% ointment for age related and solar related lesions on my scalp with good effect. Since the powder is red, can see that it is well dispersed in the white ointment

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on the thinning front hairline and crown as well as my face and hands

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I used 3mg for my 3.5oz Aquaphor cream. I’ll try higher concentration for my next batch.

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16mg in 400mg Aquafor? Did you mean 400 grams of Aquafor, or some other amount? Thanks!

Sorry that’s a typo, it’s 400 grams of Aquafor for sure

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I read the link suggesting rapamycin may not be that good for the skin last week and skimmed through it again today. Correct me if I am wrong, but it appears to have been for only 5 days with ex-vivo skin samples, and the funding was by a company with vested interests in having their product appear to be the best option. Their conclusions may be valid, but I am skeptical.

The study was funded by OneSkin, Inc., and supported by the Brazilian agencies FAPESP (2017/22057-5 e 2017/01184-9), CAPES, FAPDF, FUNDECT and CNPq.

Yes, I am skeptical.

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Skepticism is always appropriate when it comes to corporate-funded research.

However, given that rapamycin is the most well-known anti-aging molecule, but there is no commercial skin cream with rapamycin that they would be competing against (and only the really extreme geeks would know that topical rapamycin has even even been tried)… it doesn’t seem to me that lying or cheating on this type of analysis is going to be of much value. Its not like most people are comparing a non-prescription peptide cream to a rapamycin cream - so there is not much incentive to scam us on this…

The specific results:

“Rapamycin induced a significant increase in P16 expression, a trend towards increased expression of inflammatory markers (IL6 and IL8), and a significant decrease in Keratin 1 gene expression levels (Fig. 3B).

Are ultimately pretty easy to validate for anyone who has a lab, it seems.

I did try rapamycin cream I made for 6 months - saw a small improvement, but not sure if its worth it , even if it was not harming the skin via inflammation, and decreasing keratin 1 gene expression…

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I read through my comments and see your points. No implication of lying or cheating was meant. I have no doubt their results could easily be verified by other researchers. My skepticism is strongly related to how good a 5 day trial with ex-vivo skin samples can be. I would prefer a 6 months to 12 months trial using the skin cream on a large group of living humans, preferably not sponsored by any special interests. Is that likely? Well, probably not.

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Yes - sadly, not much gov’t funded cosmetic dermatology research… so we have to take what we have…

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I’d trust the study performed with an actual rapamycin cream formulation, done over a period of 8 months, in humans, placebo controlled and blinded, showing positive anti-aging effects way more than the negative study, which was in vitro using cells from cadavers and looking at 100 nM concentration of rapamycin over a 5 day period. There’s just no comparison, IMO.

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I’ve been using the higher concentration of 16mg rapamycin in 3.5oz Aquaphor for almost three months, and I’ve continued to notice a slight creeping forward of my previously-receding hairline (< 1/2"), a little higher hair density, perhaps slight darkening, and a little kinkiness to the hair when there was none before. No dramatic effects, but it seems to be adding up over time.

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I get that LC Labs’ rapa isnt USP, but has anyone had experience with their product or know of that distributors reputation / reliability?

Thanks

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They seem legit - I’ve used them to purchase the rapamycin powder and it came quickly and seemed to be the real thing (I did not have it analyzed / validated at a lab) - and worked well in the skin cream I made with it, at least as well as you might expect.

They are a lab supply company - so you can only buy from them if you work in a lab , or organization that typically can buy reagents and lab supplies…

The instructions are above - blend in transcutol and then in your face creme of choice (e.g. cetaphil).

Also - last night one of our members here - @Jay sent me this document that may be a better approach. As Jay mentioned:

The article notes the standard method is to mix Rapamycin with Transcutol, then mix with Excipial cream with an expected life before degradation of around 3 months. But, it also tells how to make a possibly better and more effective cream that lasts a year with little degradation. It takes careful reading which can be frustrating.

Full Paper: Long-term stability of 0.1% rapamycin hydrophilic gel in the treatment of facial angiofibromas (PDF)

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I’ve had good luck with mixing the powdered pills with 3.5oz Aquaphor. When I got the transcutol, I added enough to make it 2% of the total volume. The consistency and uniformity is good, except for some annoying unmixed bits from the surface of the tablets. I’m using it at a pace to finish it in 3 months.

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New way to improve skin?

Interesting new research:

Full Paper:

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Interesting, but for years I donated blood – for health purposes. High iron is an independent risk factor for cardiovascular disease.

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