Senolytics Topically Administered to Skin for Antiaging Effects

#102

With Brad Stanfield I agree. Whatever he is doing is not working as well as he would probably like.

#103

I just looked him up. His skin looks alright no?

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#106

Hi desertshores- wondering what form of Dasatnib you are using. The only one I have is tabs which I’m thinking wouldn’t be the best for dissolving into a skin formula. Do you have a powder? If so, source? Thanks…

#107

Much about what I am going to say was discussed in earlier threads, but in case you missed it:

Steps I use in making a dasatinib spray solution.

  1. Crush up your dasatinib tablets in a mortar and pestle. I use this one that I bought from Amazon.

  1. Dissole dasatinib in 30ml Transcutol+DMSO. Allow the mixture to set awhile, stirring occasionally so that the dasatinib gets dissolved. There will some things in the tablet, like titanium dioxide that won’t dissolve. These will be filtered out later. Last batch I used 10ml DMSO and 20ml Transcutol.

  2. Then add 70ml distilled water. (I actually just use bottled drinking water)

  3. Mix and then filter. I use a small funnel and some coarse filter paper. (Yes, you could use coffee filter paper)

We just want to filter out any undissolved particulate that might clog our application sprayer.

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  1. Put into small mist/spray bottles. Here are the ones I use, again from Amazon:

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Disclaimer: I don’t actually know the best concentration or the best ratios for the mixture. It is purely experimental and I am not recommending it to anyone.

“Based on the solubilizing properties of Transcutol and the poor water solubility of Dasatinib, it is very likely that Transcutol would be an effective solubilizing agent for Dasatinib”

“Dasatinib can be dissolved in DMSO at concentrations up to 200 mg/mL”

You might add a little DMSO to your solution to ensure the dasatinib is fully dissolved

.

TranscutolÂŽ

(Diethylene Glycol

Monoethyl Ether): A Potential

Penetration Enhancer

https://sci-hub.se/10.1007/978-3-662-47039-8_12

Topical administration of the pan-Src kinase inhibitors,

dasatinib and LCB

https://sci-hub.se/10.1111/bjd.12069

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#108

Oh, I meant Retin A. What is usually prescription strength? Thinking of ordering from India maybe.

#109

I use 0.1% tretinoin.

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#110

A new paper

Combined dasatinib and quercetin treatment contributes to skin rejuvenation through selective elimination of senescent cells in vitro and in vivo

The skin’s protective functions are compromised over time by both endogenous and exogenous aging. Senescence is well-documented in skin phenotypes, such as wrinkling and sagging, a consequence of the senescence-associated secretory phenotype (SASP) that involves the accumulation of senescent fibroblasts, chronic inflammation, and collagen remodeling. Although therapeutic approaches for eliminating senescent cells from the skin are available, their efficacy remains unclear. Accordingly, we aimed to examine the effects of dasatinib in combination with quercetin (D + Q) on senescent human skin fibroblasts and aging human skin. Senescence was induced in human dermal fibroblasts (HDFs) using approaches such as long-term passaging, ionizing radiation, and doxorubicin treatment. The generated senescent cells were treated with D + Q or vehicle. Additionally, a mouse-human chimera model was generated by subcutaneously transplanting whole-skin grafts of aged individuals onto nude mice. Mouse models were administered D + Q or vehicle by oral gavage for 30 days. Subsequently, skin samples were harvested and stained for senescence-associated beta-galactosidase. Senescence-associated markers were assessed by western blotting, reverse transcription-quantitative PCR and histological analyses. Herein, D + Q selectively eliminated senescent HDFs in all cellular models of induced senescence. Additionally, D + Q-treated aged human skin grafts exhibited increased collagen density and suppression of the SASP compared with control grafts. No adverse events were observed during the study period. Collectively, D + Q could ameliorate skin aging through selective elimination of senescent dermal fibroblasts and suppression of the SASP. Our findings suggest that D + Q could be developed as an effective therapeutic approach for combating skin aging.

paywalled

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#111

@RapAdmin this was interesting. It looks like a promising avenue for drug development (or reuse). I was particularly interested in the idea that ongoing “infections” (herpes virus) could be having an effect on human health. This was not the subject of the presentation but was mentioned as a thing.

I recall @ConquerAging believed the accumulation of damage (or left behind changes?) from past infections played a role in the decline of health with chron aging (time).

Is it a damage thing (accumulating scenescent cells), an immune system over activation thing (inflammation, autoimmune), or what? Does anyone have a theory?

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#112

I thought this was quite interesting and might point to the cause.

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#113

I tend to think of scarring as actually being a failure of cells to fully differentiate where they end up as senescent. That I think also applies to organs such as the kidneys.

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#114

Dang! Well back to the lab to try out a new skin spray :sweat_smile:
D+Q+Transcutol+water.
There is hardly anything that broadcasts that you are old as much as your skin.

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#115

Fashion sense? I find that my wardrobe has fallen out of fashion….and I think what is popular now looks silly. I’ll bet that makes me look old, eh?

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#116

I think this is one of the key psychometric biomarkers of aging :smile:

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#117

What formulations are people planning with respect to Desatanib / quercetin here? It looks very promising for a spot test anyway.

#118

Consider such clothing to be senescent and purge it!

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#119

A mundane question please. Where do you buy Transcutol? I am not finding it for sale anywhere online anyway.

Also, I notice many different kinds of Transcutol listed. Transcutol, Transcutol P, Transcutol Gattefosse.
What brand / type are you buying?

#120

More info in the above thread. I buy mine from Lotion Crafters.

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#121

My plan (I’m working this summer on gathering up all the compounds) is dasatinib (no querciten as it likely stains the skin) plus:

Strong potential senolytics including:

  • Sertraline
  • Fluvoxamine
  • Nortriptyline
  • Verapamil
  • Amiodarone

as per this post here: Senolytics Topically Administered to Skin for Antiaging Effects - #30 by RapAdmin

Mixed with transcutol as done in the DIY rapamycin thread: DIY Rapamycin skin cream

Then added to CeraVe body cream for final application.

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