I was listening to the David Sinclair podcast that touched on gray hair and he mentions that he thinks that what might be happening with the compounds like tacrolimus, cyclosporin, rapamycin, etc. when they are applied in a topical manner to the scalp and reverse the gray hair is that they are sending “adversity memetic” signals to the stem cells which causes the skin stem cells (melanocytes) to reset. There are obviously other types of skin stem cells besides melanocytes, and it would seem that a topical application that made the melanocytes function in a more youthful manner might also be helpful for all skin stem cells.
So perhaps there is value in applying this type of serum to other areas of skin. Anyway - it seems like something that we may want to test at some point. And if you’re creating a hair growth / gray-reversing topical formulation, please try it on other areas of skin and let us know if you notice any difference.
I’m thinking of trying this on one side of my face, and on one hand for 6 months (do pre and post photos of each) and then compare results. I’ve posted my ideas on the process / procedure for creating this topical serum here: DIY Rapamycin skin cream - #38 by RapAdmin
I believe I understand ( apologies for my ignorance to you all experts) that Tacrolimus is an analogue to sirolimus ; however I should only look for sirolimus cream 0.003 -0.004% for topical use? And not tacrolimus cream?
I found that here in Spain tacrolimus ( also under brand name:protopic ) cream is available in pharmacies ( in different “sizes” including 0.03 as the lowest ) but nevertheless I read many negative comments from long time users :
Do I understand it correctly that for topical use, I should only search for sirolimus ? Which would not have those side effects?
I would rather not invest time and money in buying stuff to make it myself before being convinced so I tried to find sirolimus cream to be delivered in Spain but the only thing available seems to be tacrolimus/ protopic )
Actually - and I’ve made the same mistake in the past - its not.
There are two drugs that are very similarly named, but are quite different.
Temsirolimus is the mTOR inhibiting rapamycin / sirolimus analog (rapalog).
Tacrolimus is not a specific mTOR inhibitor. Its an immune supressant, but slightly different mechanism as far as I can tell.
Oh - and by the way - this thread has a much deeper discussion on this combination of drugs that are discussed in the video above: Reverse Gray Hair, Hair Repigmentation
Ah ok thanks a lot - I must have misunderstood Sinclair then - apologies
And the right amount I should try to find in the EU of sirolimus cream seem to be : 0.004? Or 0.04? Or 0.04%? Or are these synonyms?
So sorry but trying to make sure I got it well as I read different quantities throughout the different blog sections
Thank you very much
I don’t think you’ll be able to find any groups selling sirolimus cream. In the US, until very recently it was only available by special order from compounding pharmacies.
In the past year a few groups in the US have started selling it. There has only been one study on rapamycin / sirolimus cream as it relates to skin aging - and I’ve seen a large range of dosings in the research (where they use rapamycin to help in other skin conditions…). So - we don’t really know much about the optimal percentages of sirolimus for skin. See details here: Rapamycin May Slow Skin Aging (Drexel U. Study)
Its injection, and I think has only recently gone off-patent, so its been difficult to buy and use, but may be interesting to learn more about if what you say is true. The issue I suspect is that even though Termsirolimus is classified as an mTORC1 inhibitor - just as all rapalogs are, just as sirolimus does over time, it may inhibit mTORC2 with prolonged, higher doses, just as rapamycin does.
That is my suspicion … but it needs to be validated…
Rapamycin (also named sirolimus, Wyeth) and other rapalogues including temsirolimus (CCI-779, Wyeth), everolimus (RAD001, Novartis Pharmaceutical), and deforolimus (AP23573, Ariad Pharmaceutical) are macrocyclic lactones acting as anticancer agents that target mTOR in several human cancers in vitro and in vivo. The main differences between rapalogues lie in changes in chemical properties in terms of drug solubility and metabolism. As a result, temsirolimus and deforolimus are water soluble and may be administered intravenously, whereas rapamycin and everolimus display low solubility, and therefore are available only for oral formulations. Rapalogues bind very similarly to the intracellular immunophilin-, FK506, binding protein-12 (FKBP12) and selectively inhibit mTORC1, but have no direct effects on mTORC2. Potency to inhibit mTORC1 seems to be identical across rapalogues. The inhibitory effects of rapalogues on mTORC1 do not seem to affect the kinase activity of mTOR. Although limited experiments have been carried out to benchmark and address cross-resistance between rapalogues, similarities in terms of chemical structures, mechanisms of action, affinity for the target, and overall spectrum of activity in laboratory experiments strongly suggest that currently developed rapalogues are similar in many ways, the main differences belonging to pharmacokinetic properties rather than to antitumor potency.
