The One Skin OS1 product is a something they are calling a senolytic peptide. I heard in interviews with the founder that they went with peptides so they could avoid the long and expensive process of FDA approval that they’d incur if they went for a drug solution. But, it seems there are likely many drugs on the market that may already be available and that are senolytic compounds that are available but not yet used in skin creams (or are generic and therefore nobody will ever fund the trials to see if they work as skin creams).
Here is some more research I’ve come across regarding senolytics like dasatinib and skin aging. I have not yet found any research papers (that I can access) where they’ve tested the most tested senolytic drugs in any topical formulations… e.g. Dasatinib, Quercetin, Fisetin and Navitoclax. Seems like something that would not be very hard to try in a formulation. Ideally pre and post tested with something like the Visia skin scanner as I described here.
Background
Skin ageing is caused by numerous factors that result in structural and functional changes in cutaneous components. Research has shown that senescent cells are known to accumulate in skin ageing, however, the role of senescent cells in skin ageing has not been defined.
Objectives
To elucidate the role of the senescent cell in skin ageing, we evaluated the effect of known senolytic drugs on senescent dermal fibroblasts.
Conclusions
Taken together, our results indicate that selective clearance of senescent skin cells can attenuate and improve skin ageing phenotypes and that senolytic drugs may be of potential use as new therapeutic agents for treating ageing of the skin.
Attenuation of intrinsic ageing of the skin via elimination of senescent dermal fibroblasts with senolytic drugs
Its a good question. OneSkin suggests daily application of their senolytic peptide based cream… but I’m sure its much less potent than the senolytic drugs like dasatinib. But as far as what is optimal, its anyone’s guess. I think the best approach may be to test out different schedules on different hands, or areas of skin, photograph in the same light/distance every 2 months, and see if one schedule seems better in terms of results than the other, then continue to test.
I agree, though speaking as one who has tried, it is devilishly hard to get valid serial photos without a bespoke set-up unless there is a large difference in effect.
Your link from FightAging! Includes this important quote related to topical Rapamycin and OneSkin.
Interestingly, the OneSkin folk used rapamycin as a positive control, and found it worsened aspects of their skin models even as it lowered markers of cellular senescence - so perhaps not something to dive into until more data has accumulated.
Looking at the meat of the data in this preprint, peptide 14 performs as well or better than topical rapamycin in reducing markers of cellular senescence, at least in skin models and in skin biopsies taken from older volunteers. Formal trials and resulting human data are pending - though the product is available for anyone who wants to give it a try. Given the existing data, it will be interesting to see how the product performs in older people in comparison to topical rapamycin use.
That is true. I’ve pointed that out here in this post, and I’ll repeat it here:
But there is also research that suggests rapamycin may not be that good for the skin, increasing inflammatory markers (which is not a good sign), and triggering a breakdown of the extracellular matrix:
"Rapamycin is a long studied molecule affecting mTOR/nutrient signaling and has recently been shown to decrease P16 levels of aging skin21, therefore it was chosen as a positive control of senotherapeutic effect in aging skin models. " … “Rapamycin induced a significant increase in P16 expression, a trend towards increased expression of inflammatory markers (IL6 and IL8), and a significant decrease in Keratin 1 gene expression levels (Fig. 3B). In the dermis, peptide 14 treatment promoted a significant reduction in B2M gene expression, a pro-aging factor, as well as in the expression ofIL8. Rapamycin treatment induced no significant changes in these markers and increased Matrix Metalloproteinase-1 (MMP1) gene expression, indicative of breakdown of the extracellular matrix (Fig. 3C).”
Another compound that may be something we want to consider adding to a skin cream for anti-aging.
Glutaminase inhibitors rejuvenate human skin via clearance of senescent cells: a study using a mouse/human chimeric model
Skin aging caused by various endogenous and exogenous factors results in structural and functional changes to skin components. However, the role of senescent cells in skin aging has not been clarified. To elucidate the function of senescent cells in skin aging, we evaluated the effects of the glutaminase inhibitor BPTES (bis-2-(5-phenylacetamido-1, 3, 4-thiadiazol-2-yl)ethyl sulfide) on human senescent dermal fibroblasts and aged human skin.
BPTES selectively eliminated senescent dermal fibroblasts regardless of the method used to induce senescence; aged human skin grafts treated with BPTES exhibited increased collagen density, increased cell proliferation in the dermis, and decreased aging-related secretory phenotypes, such as matrix metalloprotease and interleukin. These effects were maintained in the grafts 1 month after termination of the treatment. In conclusion, selective removal of senescent dermal fibroblasts can improve the skin aging phenotype, indicating that BPTES may be an effective novel therapeutic agent for skin aging.
As of July 2018 some glutaminase inhibitors are in mid-stage clinical trials. In 2021, it was reported that a GLS1 inhibitor eliminated senescent cells from various organs and tissues in aged mice, ameliorating age-associated tissue dysfunction. Results suggest that senescent cells rely on glutaminolysis, and inhibition of glutaminase 1 may offer a promising strategy for inducing senolysis in vivo.
We found that ABT-263 and ABT-737 induced selective clearance of senescent dermal fibroblasts, regardless of the method of senescence induction. Aged mouse skin treated with ABT-263 or ABT-737 showed increased collagen density, epidermal thickness, and proliferation of keratinocytes, as well as decreased senescence-associated secretory phenotypes, such as MMP-1 and IL-6.
Conclusions
Taken together, our results indicate that selective clearance of senescent skin cells can attenuate and improve skin ageing phenotypes and that senolytic drugs may be of potential use as new therapeutic agents for treating ageing of the skin.
Cellular Senescence and the Senescence-Associated Secretory Phenotype as Drivers of Skin Photoaging
Chronic exposure to UVR is known to disrupt tissue homeostasis, accelerate the onset of age-related phenotypes, and increase the risk for skin cancer—a phenomenon defined as photoaging. In this paper, we review the current knowledge on how UV exposure causes cells to prematurely enter cellular senescence. We describe the mechanisms contributing to the accumulation of senescent cells in the skin and how the persistence of cellular senescence can promote impaired regenerative capacity, chronic inflammation, and tumorigenesis associated with photoaging. We conclude by highlighting the potential of senolytic drugs in delaying the onset and progression of age-associated phenotypes in the skin.
I have still not seen anything that is better for photoaged skin than Retin A (tretinoin). IMO, only the prescription strengths are worth the money. Fortunately I have a prescription, but if I didn’t I sure would import some from India.
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.
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.
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:
Choose a work space away from food, windows, and fans. Clean the area and place items needed on a paper towel.
Wash hands and put on gloves
Fill a drinking glass with 1 ounce or 30 ml of chilled orange juice or apple juice (without preservatives).
Place the number of tablets required for the dose into the glass of juice.
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.
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.
