Senolytics Topically Administered to Skin for Antiaging Effects

Yes - I think the risk is also much lower with regard to initiating use of senolytics (compared to oral use). Start with the skin, the effects are visible (if there are any) and if they cause any negative reaction its easy to see and you can stop using it if there is.

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Is there a good senolytic cream that can be applied to the scalp to increase hair growth? I am interested to try this!!!

Not available commercially - but you could make your own with all the known senolytics that research groups have identified. Follow the DYI rapamycin cream instructions, but use the senolytics instead. I plan to do this for skin.

Its interesting, I don’t think anyone will ever make this product as a commercial product (or at least for the next decade)… the current senolytic drugs are all generic, so difficult to charge much for them. But, a very cheap (and potentially effective) skin cream for much less cost than simple skin creams.

There are so may senolytics, I would love to know which senolytic molecules would you try first? And your reason?

I still have some Dasatinib in my refrigerator, and I have used topical Retin A(tretinoin) for years, Retin A is believed the most powerful anti-aging topical drug so far, it would be interesting to compare the potency of Retin A with Dasatinib on myself, but I am worry if topical Dasatinib results in systemic absorption? I can’t find data about it.

In the study using transcutol and rapamycin in formulation of a skin cream, they tested for systemic absorption of the rapamycin and saw none, so I think generally you are unlikely to get systemic entry of the drug based on transcutol-based skin cream formulations.

Dasatinib is an obvious first try for a senolytic skin cream.

Also: Navitoclax (ABT-263) rejuvenates human skin by eliminating senescent dermal fibroblasts in a mouse/human chimeric model - PubMed

and: Glutaminase inhibitors rejuvenate human skin via clearance of senescent cells: Mouse/human chimeric model study

Perhaps also fisetin, and quercetin?

and I have some more information coming soon from the conference I went to this past week.

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Thanks for sharing and waiting for more information coming from the conference.

Dasatinib can’t dissolve in transcutol, it looks like Dasatinib slightly soluble in ethanol, methanol, polyethyleneglycol 400 and propyleneglycol, and in one guide for child who can’t swallow Dasatinib, they put Dasatinib in the water for 5 minutes, then stirring it for 20 minutes.

I don’t know what’s the optimal concentration to prepare, are there any thing to reference?

Dasatinib is a crystalline white powder and exhibits pH dependent aqueous solubility (from 18.4
mg/ml at pH 2.6 to 0.008mg/ml at pH 6.0). It is very slightly soluble in acetone and acetonitrile and
slightly soluble in ethanol, methanol, polyethyleneglycol 400 and propyleneglycol. It is practically
insoluble in corn oil.

Dasatinib is characterized as a low solubility/high permeability (BCS II) compound according to the
Biopharmaceutics Classification System (BCS). In this context, dissolution of dasatinib can potentially
be rate-limiting for absorption.

For children who cannot swallow tablets:

  1. Choose a work space away from food, windows, and fans. Clean the area and place items needed on a paper towel.
  2. Wash hands and put on gloves
  3. Fill a drinking glass with 1 ounce or 30 ml of chilled orange juice or apple juice (without preservatives).
  4. Place the number of tablets required for the dose into the glass of juice.
  5. Let the tablets sit in the water for 5 minutes. Then begin stirring. Stir until all tablets are dissolved which may take up to 20 minutes.
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RapAdmin, Yes, Dasatinib! That’s exactly what I was thinking, but at what strength? If you’re going that route pass along your thoughts on ingredient mixing when you have time. Thanks.

Dr. Garcia has a rapa cream (via compounding pharmacy) which I also purchased like 6 months ago, my skin got worse. Now even with a retinal, my skin got much worse and then better, perhaps I didn’t give it enough time? So, I can honestly say, my skin is softer on OneSkin (no I don’t work for them or benefit), I can’t send a pic of that but I can assure you that’s a fact. I feel like a skin expert in trying different things. I’ve reordered OneSkin, gave it as a Christmas gift to my sister, but I’m always open to experiment a little. Recently, I started experimenting with Droplette, too early for any opinion.

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So - we may have a few more candidates for senolytic drugs that people can test for topical application for skin (since it seems much more safe to do this, than to be using them orally, until more testing).

Strong potential senolytics that I’m thinking of adding to my Senolytic skin cream include:

  • Sertraline
  • Fluvoxamine
  • Nortriptyline
  • Verapamil
  • Amiodarone

At the Longevity Summit at the Buck Center in December, Tim Peterson presented on his group’s work on senolytics. Tim is very focused on the longevity space, and did work in the Sabatini Lab working on mTOR.

It seems that there is a class of drugs that can be identified as “cationic amphiphilic drugs” that seem to be powerful senolytics. Many of these are generic psychiatric drugs (@DrM ) that are inexpensive and widely available (from US or Indian pharmacies, etc). I may try adding these to my planned senolytic skin cream that I’m going to create with Dasatinib in it, similar to how we’ve created the DIY rapamycin skin cream. Comments back from people who are knowledgeable about these drugs greatly appreciated.

Their project, described on Tim Peterson’s Lab website: https://timrpeterson.wustl.edu
Is as follows:

Senolytics are a powerful new class of longevity therapeutic.

They selectively kill disease-causing senescent cells that accumulate in our bodies as we age. In this project we will test a class of drugs we identified called cationic amphipathic drugs (CADs) that we’ve shown in preliminary studies to have powerful senolytic activity. Based on the drugs’ chemistry we propose this class acts like an intracellular soap to ‘clean out’ these ‘old’ senescent cells from the body. Because many of the drugs we’re testing are already in use in humans and are inexpensive, and we will make our results publicly available, our goal is to accelerate the longevity field by providing immediately useful therapies.

More details on the Open Senolytics program: Open Senolytics

Who is the team behind Open Senolytics?

Our team is led by Tim Peterson, Ph.D. and Sandeep Kumar, Ph.D. Dr. Peterson is an Assistant Professor at Washington University School of Medicine in St. Louis in the Departments of Medicine and Genetics. “WashU” is a perennially top five medical school in the U.S. in terms of publishing and funding. Dr. Peterson did his Ph.D. at MIT where he published multiple papers in Nature, Science, and Cell journal on one of the major aging pathways, mTOR, and the drug, rapamycin, that targets it. Dr. Peterson did his postdoctoral fellowship at Harvard University where he continued his work on longevity drug mechanisms focusing on the most commonly used drugs for osteoporosis, bisphosphonates and diabetes, metformin. Dr. Kumar similarly has a deep background in aging research most notably performing several seminal lifespan studies in worms.

Dr. Morten Scheibye-Knudsen at the University of Copenhagen will be assisting us with his AI-driven senescent cell detection algorithms (see below). These algorithms are helpful because they allow us much greater throughput in our experiments. Thus, we can test many more CADs.

A sample of some of the slides that Tim presented are below:

Substances with antihistamine and cationic amphiphilic characteristics, with potential (or confirmed) anti-SARS-CoV-2 activity

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830196/table/t0005/?report=objectonly
Paper Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830196/

Psychotropics with antihistamine and cationic amphiphilic properties and potential anti-SARS-CoV-2 activity (FIASMAs +/−) Preliminary data confirming anti-SARS-CoV-2 activity
Alimemazine/trimeprazine (−‡) [13]
Amitriptyline (+) [8]
Astemizole (+)
Benz(a)tropine (+) [18]
Cetirizine (−)
Chlorphenoxamine (−)
Chlorpromazine (+) [16], [18], [19]
Citalopram* (−)
Clomipramine (+) [19]
Clozapine (−)
Cyamemazine (−‡)
Escitalopram* (−) [8]
Flupent(h)ixol (+) [13]
Fluphenazine (+) [19]
Fluspirilene*(−#) [19]
Hydroxyzine (+) [17]
Levomepromazine/methotrimeprazine (−‡)
Mequitazine (−‡)
Metopimazine (−‡)
Penfluridol* (+)
Pimozide* (+) [21]
Pipamperone*(−)
Pipotiazine (−‡)
Promethazine (+) [19]
Perici(y)azine/propericiazine (−‡)
Quetiapine (−)
Tiethylperazine (−‡) [19]
Tiotixene (−‡)
Triflupromazine (+)
Zuclopenthixol (−‡)

Representative examples of cationic amphiphilic drugs that are identified in SARS-CoV-2 drug repurposing screens.

Source: https://www.researchgate.net/figure/Representative-examples-of-cationic-amphiphilic-drugs-that-are-identified-in-SARS-CoV-2_fig1_350363085

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https://www.biospace.com/article/antidepressant-fluvoxamine-potential-early-treatment-for-covid-19/
I had heard about fluvoxamine (Luvox) for OCD had benefits in early COVID. The MOA with so many medicines is speculated and probably often wrong or multifactorial. For example, the Selective Serotonin reuptake blocker theory of depression is slowly coming apart. So I am not surprised they can be repurposed for other tasks, including senolytic purposes.

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More reasons to think that topical senolytic skin cream may be a good thing:

Navitoclax (ABT-263) Rejuvenates Human Skin by Eliminating Senescent Dermal Fibroblasts in a Mouse/Human Chimeric Model

Chronic senescence, such as aging, contributes to age-related tissue dysfunction and disease development. The accumulation of senescent fibroblasts and the senescence-associated secretory phenotype is particularly implicated in this process. Removal of senescent cells has been reported to prevent tissue dysfunction and to extend the life span during aging. ABT-263 (navitoclax), which inhibits antiapoptotic proteins, is a leading antiaging drug; however, its role in human skin aging is unclear. This study aimed to determine the rejuvenating effects of ABT-263 on aging skin using a human skin graft mouse model. We assessed the viability of ABT-263-treated skin fibroblasts after inducing senescence. Aged human skin was transplanted under the back skin of nude mice and injected intraperitoneally with the drug or control. Analysis of the skin specimens revealed that ABT-263 induced selective elimination of senescent dermal fibroblasts. Senescent human skin treated with ABT-263 exhibited a decrease in the number of senescent cells and in the expression of aging-related secretory phenotype molecules, such as matrix metalloproteinases and interleukins and an increase in collagen density. Our results indicate that selective removal of senescent skin cells with ABT-263 can improve the aging phenotype of human skin without side effects. ABT-263 is, thus, a novel potential therapeutic agent for skin aging.

https://www.liebertpub.com/doi/10.1089/rej.2022.0048

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