wrinkle reduction

has anyone noticed wrinkle reduction in systemic use of sirolimus?

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    • Michael
    • Michael.1
    • 3 yrs ago
    • Reported - view

    Does anyone have the actual formula to make it? Would this be a good candidate? https://www.dropshipmd.com/buy/rapacan/ -

    Thank YOU!

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    • Michael So you mixed in 4mg into 4 ounces of cream? I know it seems like a weak formula but people are getting results, granted it takes 2-3 months though. Mark points out more is not better and he says just apply it twice a day for faster results. But something still bugs me about it though, it would seem to make more sense having a stronger formula that is applied less often rather than a weak formula more often. But for now, I am using a 3mg per 4 ounce solution and have been for two months.

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      • Michael
      • Michael.1
      • 3 yrs ago
      • Reported - view

      Fred Cloud I only ended up adding another mg as there was unintended loss after transferring the diluted rapa/dmso into the 4 ounces of Arbo Trex Dmso/Aloe Vera cream. The truth is I wasn't expecting it to arrive so quickly and in my excitement, began following your formula with a make-shift, bob-the-builder set-up. Thanks again for providing that formula above.

      I agree with you that less is more- initially for sure. But I also feel much faster results would be obtained with potentially 2 ounces of medium or... something. 

      I did want to ask if you've noticed any difference since you've begun applying it twice a day AND beyond this cream, are you also taking rapa in pill or sublingual, and if so, how much weekly?

       

      Thanks again!

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    • Michael I have been taking 3mg rapa weekly and using the topical rapa for 2 months and I havent noticed a difference yet in my skin. But I am not panicking yet because Paul Beauchemin mentioned he didnt notice changes until 3-4 months.

      Having said that, it has been life changing to me in terms of my health, I feel completely different and feel about 10 years younger in terms of inflammation and overall age of my body.

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      • Michael
      • Michael.1
      • 3 yrs ago
      • Reported - view

      Fred Cloud Right on, brother!

       

      It's been a shitful year for me health-wise (outside of losing tons of weight and bodyfat via massive amounts of light, endurance exercise) with Carcinoma. I'm hoping for a like benefit in the skin arena. I'm giving it 3 months then going full bleph. 

       

      #blephbros

      Like 1
      • garland
      • garland
      • 3 yrs ago
      • Reported - view

      Michael  not sure what you mean. I used the DMSO from Heiltropfen from Germany as my medium to absorb the Rapa. I put it into a test tube about one third full and then added the Rapa to it. Remember I first put the Rapa in a motor and pistol and thoroughly ground it up. Then when I put this mixture in the DMSO liquid in the test tube  I then shook it up thoroughly. DMSO is a great absorber of chemicals so it absorbed the Rapa as I could see the mixture get cloudy. I then poured this liquid cloudy mixture into a bowl of the 4 oz DMSO/ALOE cream to mix it up thoroughly. It mixed easily  so I do not feel that this mixture was haphazardly created. I used enough  liquid DMSO mixture to make sure that this product was easy to mix in the Cream DMSO/Aloe.... IS that what you did...

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      • Michael
      • Michael.1
      • 3 yrs ago
      • Reported - view

      garland I appreciate your formula. I ordered the exact same items. I think I probably just didn't use enough Heiltropfen.  Thank you!

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      • garland
      • garland
      • 3 yrs ago
      • Reported - view

      Michael Yea I used alot of it so it would mix well....

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      • garland
      • garland
      • 3 yrs ago
      • Reported - view

      Michael You also have to ground up the pills very finely.... makes it easier for the DMSO to absorb it... meaning the liquid DMSO not the Cream..

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      • Michael
      • Michael.1
      • 3 yrs ago
      • Reported - view

      garland Yes. I bought the mortar which made grinding it down extremely easy. I just didn't use enough liquid DMSO before adding to the cream. I appreciate you!

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      • Michael
      • Michael.1
      • 3 yrs ago
      • Reported - view

      Fred Cloud Any update on noticeable differences? Thank you.

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      • Michael
      • Michael.1
      • 3 yrs ago
      • Reported - view

      garland Any update on efectiveness? Thank you

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    • Michael month 3 and not much change, but I did not use dmso. I may add dmso to the mix, it may be needed for deeper dermal layer penetration. Did you start on rapamycin oral or topical?

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      • Michael
      • Michael.1
      • 3 yrs ago
      • Reported - view

      Fred Cloud Thank you, bro.  I started on the cream - nothing yet. I started 3mg a week of the pill and believe some nasty lung / flem stuff happened from the pill so, probably will discontinue use. On a different note I started up the Kaufman protocol - every stinking pill. Loads of energy!

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    • Michael I followed exactly the recipe posted by Mark Thimineur, but I made a double quantity using three 2mg Sirolimus tablets that I ground up with mortar and pestle. The dissolved sirolimus mixed easily but I think a little more DMSO liquid would have been even better. I took baseline measurement with the skin fold test on one hand and took photos of my cheeks and forehead as well as the sagging skin on my upper arms. I've been applying twice a day for 10 days. I stopped all oral sirolimus since it seemed to interfere with healing of a slow healing wound. I will document and post progress, if any, after a few months.

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      • Michael
      • Michael.1
      • 3 yrs ago
      • Reported - view

      chuck stanley Thank you, Sir! I look forward to seeing your results.

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      • Michael
      • Michael.1
      • 3 yrs ago
      • Reported - view

      Fred Cloud My update on this so far is nothing positive - potentially worse as I'm applying in under eye area. Stopped taking rapa - just using rapa cream. 

      I've maintained an excellent diet. OMAD. Cut back on Whiskey (Painful). Practically zero carbs and sweets. Back to at least 1000 calories a day combination treadmill/ walking with light weights. Focusing more on core: heavier-side squats.

      Looks more and more likely a bleph is in my immediate future. 

      Like 1
  • 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?
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    • Michael
    • Michael.1
    • 3 yrs ago
    • Reported - view

    Sorry. I confused Fred with Garland. lol Oh, what a day!

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    • Michael
    • Michael.1
    • 3 yrs ago
    • Reported - view

    I can't play chess to save my life today, either.

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  • 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 [613]. 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 [1830] 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 [3436]. 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 [18,3739], numerous studies have confirmed that rapamycin extends lifespan in mice (see for references [4044]).

    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.

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    • David H
    • David_Hanson
    • 3 yrs ago
    • Reported - view

    And here's a link to Rapamycin for Aging Skin article (plus I attached the pdf version):

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949048/

      • Michael
      • Michael.1
      • 3 yrs ago
      • Reported - view

      David H garland Fred Cloud What do I need to know about Rapacan vis-à-vis it's place in the rapamycin hierarchy?  Specifically, 1mg tablets. Thank you!

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  • 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

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    • @Ross Barker  Your math is off

      48 grams equals 1.69315 ounces, not 4 ounces

      .0002g is .2mg not 2mg.

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    • Fred Cloud The  first  was  a  typo,  the  bottle states  1.7  oz 48  Grams,  likewise I  added  too  many  "0"s I  Better  edit  my  original  post  OOOO,  it won't allow  me  to  Edit  it, I  added .002 G  Rapa powder to  48  G of Cream or  1.7oz,  I  can't  find  where I  said  4 oz. 

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