-
Does anyone have the actual formula to make it? Would this be a good candidate? https://www.dropshipmd.com/buy/rapacan/ -
Thank YOU!
-
This is Exciting, I'm ordering some powder off Alibaba and going to try mixing up a Skin cream for my wife, she loves that kind of stuff, might even try some for myself, I saw some info somewhere that NAC N-Acetyl-Cysteine was a big help also for Skin, I thought I would add it, does anybody here have any feeling for that stuff?
-
I just ran across this article by the rapamycin guru blagosklonny trying to patent topical rapa back in 2007, clearly ahead of his time, its an interesting read so I thought I would pass it on.
Rapamycin for the aging skin
Mikhail V. Blagosklonny
In 2007, I filed a patent application claiming that topical rapamycin (e.g., in the form of a cream or ointment) https://patents.google.com/patent/WO2008022256A2/en could be used to prevent and treat skin aging. Potential indications include various types of age-related spots, wrinkles, photo-aged skin, and other age-related skin conditions. The patent was not granted, nor were cosmetic companies interested in pursuing this avenue of product development. Cell senescence has traditionally been seen as growth arrest. It seemed weird that rapamycin, a drug that inhibits growth, could inhibit cellular senescence. Nonetheless, it works because, actually, senescence is a continuation of growth when true growth is impossible [1]; in other words, senescence is “twisted” growth [2]. In an exciting ‘twist’, these claims were recently confirmed in a clinical trial by Chung et al. [3], which I will discuss later.
Even in 2007, the idea of using rapamycin topically was not novel [4,5]. (What was novel in my application was the idea of using topical rapamycin as an anti-aging drug for the aging skin [1]). By now, there have been dozens of papers describing the therapeutic use of rapamycin (Sirolimus) in patients with such skin diseases as lymphatic malformations, vascular anomalies, Facial Angiofibroma and psoriasis [6–13]. These diseases were treated in children and young adults. In one study, topical rapamycin at low doses (0.003-0.015%) decreased facial angiofibromas in young adults. There was no systemic absorption of rapamycin (blood levels were <1.0 ng/mL) [13].
Returning to cellular senescence, signaling in the mTOR (Target of Rapamycin) pathway drives growth of cellular mass and sustains cell cycle progression. Cells grow and divide, balancing growth. But when the cell cycle is suddenly blocked by p16 or p21, mTOR drives growth-like conversion from reversible arrest (quiescence) to senescence [2,14]. In short, mTOR drives geroconversion [15]. Rapamycin and its analogs, as well as pan-mTOR inhibitors, suppress geroconversion, thereby maintaining cells in a young healthy state. Moreover, these drugs prevent loss of cells’ proliferative potential, which is considered a strict definition of senescence [2,15]. Geroconversion in stem cells leads to stem cells depletion [16,17]. mTOR-driven hypertrophy can be followed by atrophy at the end stages. Cellular hyperfunction eventually leads to cellular exhaustion and secondary functional decline [1].
Suppression of cellular senescence by rapamycin was demonstrated in numerous studies both in vivo and in vitro [18–30] and see for references [15]. In vitro, rapamycin slows conversion to senescence by approximately 3-fold [14]; it does not suppress it completely. Notably in that regard, in the most rapamycin-responsive mouse model of mitochondrial disease, rapamycin extends the maximum life span by nearly 3-fold [31].
Just as in vitro geroconversion is a continuation of growth, organismal aging is an unintended and harmful continuation of developmental growth post-development [1,32]. These messy quasi-programs inevitably lead to age-related diseases, which include conditions ranging from obesity, cancer and Alzheimer’s disease to skin spots, wrinkles and seborrheic keratoses. mTOR drives geroconversion, increasing cellular functionality (e.g., the senescence-associated secretory phenotype). It is noteworthy that this increase in cellular activity can cause secondary exhaustion, tissue damage and decreased of organ function; for example, hypertrophy may be followed by atrophy at later stages. In other words, age-related diseases and conditions initially caused by mTOR-driven hyperfunction eventually lead to organ damage and functional decline [1,33]. Similar quasi-programs were described even in the worm [34–36]. In sum, aging is an unintentional and harmful continuation of developmental programs, driven in part by mTOR. To be clear, mTOR activity does not need to increase with age, just keeping it at a level as high as during development is sufficient to cause disease. Despite its simplicity, this model accurately predicts that rapamycin will extend life and delay diseases. Indeed, since initial publications [18,37–39], numerous studies have confirmed that rapamycin extends lifespan in mice (see for references [40–44]).
In that context, it is predictable that rapamycin would slow skin aging. However, unless rapamycin reverses skin aging, not merely slow it, the effect would be difficult to document. This is because a patient cannot serve as a self-control (placebo control) unless rapamycin reverses aging, which would be easy to detect. This difficulty can be overcome, however, by comparing an untreated hand with a hand treated with topically applied rapamycin in the same subject. This is the approach taken by Chung et al. in their study, which found that treatment with rapamycin-containing cream improved skin photoaging and skin tone, decreased fine wrinkles, increased dermal volume, and reduced sagging of the skin [3]. These differences between treated and untreated hands were detectable after 4 months of the treatment [3]. Regrettably, the study excluded patients with diabetes, although the therapeutic effect would probably be more significant in diabetic patients, given that mTOR is overactivated in that disease. In addition, it is unclear whether rapamycin reversed skin aging and improved the skin or merely slowed the progression of skin aging. In the latter scenario, the difference between the treated and untreated hands is due to the progression of aging in the untreated hands. In combination with placebo/treatment, comparisons of specific abnormalities before and after treatment is also needed. Despite these open questions the study is remarkable [3].
As a cosmetic, rapamycin-containing cream may be applied to selected areas, like the hands and face, especially skin affected by age-related spots and pathologies. It should not be applied to the entire skin surface of the body. To affect the entire skin surface, systemic use of rapamycin would likely be a better option, as many manifestations of skin aging are probably due to systemic organismal aging and disease; skin aging is not an exclusively local process. And most importantly, systemic rapamycin use increases lifespan and decreases disease. This by itself is so important that solely topical use of rapamycin may seem insufficient. On the other hand, topical application of any drug is safer than systemic administration. Still, the best strategy in some cases may be simultaneous systemic and topical use of rapamycin in selected areas of the skin, especially areas where there are signs of aging marks. However, given that most doctors are fearful of systemic treatment with rapamycin [45], I expect that it will be topical use of rapamycin that becomes widespread, if regulatory hurdles can be overcome. Whether rapamycin cream should be a prescription treatment or an over-the-counter cosmetic will likely be a matter of debate.
-
I Just mixed this up, near as I could measure I used .0002 G of Rapamycin powder with 48 Grams of Cream, Please could somebody comment on my Math? it seems such a little bit, if I would take 6mg/week internally, how could 2mg topically over 3 months be sufficient for any real benefit? Did I miss something? I'm tempted to increase the dose 10x for a start? Paul, please where did you find the original concentration? @Garland I can't find your conversation with this Dr Mark
-
From Mikhail V. Blagosklonny Study
Even in 2007, the idea of using rapamycin topically was not novel [4,5]. (What was novel in my application was the idea of using topical rapamycin as an anti-aging drug for the aging skin [1]). By now, there have been dozens of papers describing the therapeutic use of rapamycin (Sirolimus) in patients with such skin diseases as lymphatic malformations, vascular anomalies, Facial Angiofibroma and psoriasis [6–13]. These diseases were treated in children and young adults. In one study, topical rapamycin at low doses (0.003-0.015%) decreased facial angiofibromas in young adults. There was no systemic absorption of rapamycin (blood levels were <1.0 ng/mL) [13].
This works out to a maximum of .72G of Rapa or 720 mg for the small 1.7oz 48G bottle of Cream I bought
-
More good news on my update... It has been over a year and few months for me.. and the eyes are about 80% better most of the deep wrinkles are now fine at worst and the left eye is almost gone. I am now doing some Retin A from Life Extension. Seems to be helping slightly,. Remember I did mostly one time a day so should have gotten better results had I done 2 a day. Forehead is 80% healed and neck the same way... the sun damage is mostly gone. Which is huge. I look according to many others 15 years younger as my skin glows and shape of my face has changed. But the most amazing thing was the changes in my creepy skin on the upper arms has reduced by over 70% and my arm is clear up til the underarm area. So this is huge as no one thought it would work on the creepy skin especially as it was very pronounced on my upper arms. That is mostly gone now...it take a long time to see any results. I am now at 15 or more months but it seems to get better and better. I also am doing Senyletics on a regular basis so that might be a factor (once a month or so...22 mgs of life extension Fisetin which has been modified to be more absorbed as well as Dasatinib 100 mgs and Quercetin for 3 straight days) ....try 2 times a day for the cream as it might happen quicker.
-
My impression of the effect of topical rapamycin on my skin is that it is effective but superficial. The elasticity of skin on the back of my hand is greatly improved from a snap back time of 4 minutes or so to several seconds. There is no improvement in facial wrinkles, however, which are getting worse despite using the formulation daily. I wonder if there is a formulation which provides greater penetration to the dermis than does the DMSO cream. There have been studies around this but I have not seen a formula which could be safely adapted and used by us.
-
After screwing around with a multitude of supplements, exercise protocols and exogenous gh/testosterone combinations to impact aesthetics, I bit the bullet and went the route of a very minor plastic surgery protocol. Guess what? I'm throwing out about 100 bottles and containers of pills and creams of useless shit on Sunday. GOOD LUCK my little, green, longevity FRIENDS!
-
Yes good point Ross.... The good thing about the cream is that it does get rid of most senelytic cells according to the research study..... so it has profound anti aging effects as well as cosmetic purposes. For me it got rid of 80 % of my wrinkles under my eyes.... and more than 60& of my crepey skin under my arms....plus it gets rid of aged cells..... and it is cheap..
-
The comments above about skin elasticity caught my attention. I haven't used the sirolimus lotion yet. I have completed about 4 months of daily collagen peptides (in a morning coffee) plus daily hyaluronic acid pills and vitamin C in the form of 1 or 2 lemons. (Sometimes I'm just making chicken bone broth instead of the collagen peptide powder, but it's mostly the powder). Alas I've also found the more expensive hyaluronic acid pills (higher molecular weight) do indeed seem to make more difference and annoy my stomach less.
Jury is still out on fine lines, I'm taking regular photos in controlled light and will report on that. What I can say though is that my skin elasticity has improved.
I'm 50 and was starting to get some sag, and pinch test on the hand would take a few seconds to revert. Now the skin on my hand reverts instantly, so there is improvement. (Also I have less sag under the chin but that could be down to fixing my metabolism this year and no longer having high insulin, water retention and all that jazz; material for another post)
I find this very heartening, as connective tissues are also supposed to benefit. Off topic I have noticed that just a week after starting collagen peptides my hip joint (post injury) stopped aching. Others online mention positive things about joint pain too.
My one concern about collagen peptides is whether this is triggering mTOR as a high protein diet would. On the bright side my particular supplement has low levels of Methionine, which might help there.
Anyhow, I post the one year difference photo below and you be the judge. Skin sag under chin gone, lines around eyes maybe a little, not sure. But there is also 18kg weight loss between photos, it's been a busy year and difficult to tease out cause and effect.