OneSkin Launches a Topical Senolytic Treatment

Senescent cells are damaging to tissue function and health when they linger and grow in number, as becomes the case with age. They contribute to the chronic inflammation of aging via their signaling, the senescence-associated secretory phenotype. In skin, senescent cells are most likely responsible for a sizable fraction of the more problematic later life skin aging, in the 50s and on. It is less clear and less likely that they have much do to with the changes seen from the late 20s into the 40s.

The primary advantage inherent in targeting the mechanisms of aging specifically in skin is that the regulatory path to market for cosmetic treatments is much, much shorter than the alternative Investigational New Drug option. Thus OneSkin is making available a topical senolytic treatment that selectively destroys senescent cells in skin, and is doing so years in advance of FDA approval of any of the programs aiming to destroy senescent cells throughout the body. (That said, the senolytic treatment of dasatinib and quercetin, shown to destroy senescent cells in humans in a clinical trial, and capable of producing significant reversal of aging and age-related disease in mice, is very much available to any sufficiently motivated individual).

It would be interesting to see concrete data on the size of the effect produced by the OneSkin treatment, but that data isn't available yet. Is this approach definitively better than the suppression of skin senescence achieved via long term topical use of rapamycin, for example? One would hope so, but we'll have to wait and see. This lack of published, detailed data on effects in humans at the time of product launch is fairly characteristic of the supplement and cosmetics industries, and it makes it hard for the public at large to tell the difference between groups that are earnest and addressing a useful mechanism versus those that are not.

OneSkin launches topical senetherapeutic skin treatment

OneSkin is a longevity company on a mission to transform the way we think about skin. Today the company is launching OneSkin, a topical supplement containing a proprietary peptide, OS-01. Designed to reduce skin's biological age, OneSkin claims to improve the skin barrier, support DNA damage repair and prevent the accumulation of senescent cells. OneSkin launched in 2016 as a biotech startup after acceptance into IndieBio, one of the world's leading science accelerators.

"Our goal was to develop a product that extends skinspan, the period of time your skin is healthy and youthful. Our roots are in longevity science and we saw a need to shift the current paradigm. Instead of short-term fixes that focus purely on aesthetics, we're targeting the root cause of aging and optimizing skin health on a molecular level. We believe what we put on our skin should be safe, effective, and help to maximize our human potential."

OneSkin operates end-to-end research and development in-house with a team of experts in stem cell biology, skin regeneration, tissue engineering, biochemistry, bioinformatics, molecular biology, immunology, and aging. They measure skinspan in with MolClock - OneSkin's first skin-specific molecular clock - and with skin aging modelling, using a proprietary technology and lab process which includes growing 3D human skin weekly and measuring how various products and ingredients influence gene expression of the many genes associated with aging and longevity.

"As we age, senescent cells begin to accumulate in our skin tissues. The accumulation of these cells can contribute to an increased presence of wrinkles, susceptibility to skin cancer, and a damaged skin barrier. Beyond its impact on skin, when left to linger, senescent cells send pro-inflammatory signals to the rest of the body, increasing the risk of age-related diseases." Preventing the accumulation of senescent cells reduces skin's biological age as measured via MolClock, as well as leading to increased epidermal thickness, improved skin structure through increased collagen production and hyaluronic acid expression, maintained skin homeostasis and cell vitality.

Comments

"Prevent" the accumulation of senescent cells? How would they do that? I smell fish...

Posted by: Barbara T. at October 22nd, 2020 1:31 PM

I'm just going to try it, maybe on one hand only, then compare hands after 12 weeks.

Posted by: Corbin at October 22nd, 2020 2:46 PM

If it is noticeable (on consumer hands), I think it'd be a huge boon for the rejuvenation industry.

Posted by: Robert at October 22nd, 2020 3:00 PM

Like Reason said, senescent cells contribution to aging have much to do from 40-50 years old until old age. Skin aging from 25 to 40 years old have more to do with sun damage and loss of subcutaneous fat and probably crosslinks.

Posted by: Jonathan Weaver at October 22nd, 2020 3:50 PM

Sorry - no thanks

Diamandis has been using his platform lately to pump all his investee companies, including this one, and his pre-clinical Covid vaccine company COVVAX

I know marketing is required to spread awareness, but i thought this new generation would be held to higher standard

On an un-related note, anyone know why Aubrey De Grey is no longer at Agex?

Posted by: devon mcradle at October 22nd, 2020 4:04 PM

Skin aging in 40s to 50s has to do with a loss or deterioration of the subdermal collagen and fat. It remains to be seen whether there will be a noticable reversal of the looks even if the sonlytics actually work and kill most of the ScC.

Posted by: cuberat at October 22nd, 2020 5:32 PM

"In skin, senescent cells are most likely responsible for a sizable fraction of the more problematic later life skin aging, in the 50s and on"
There is a study that back this claim?. I saw that you made the same claim in a former article https://www.fightaging.org/archives/2019/10/melanocytes-are-the-only-epidermal-cells-to-show-signs-of-senescence-with-aging/
and I actually wrote a comment in this article few weeks ago.
I don't think there is much of a connection between cancer risk and skin aging and there is no reason for making such correlation between skin aging and the risk of getting some disease that doesn't have much to do with the skin at all.

Advanced Glycation End products are probably the major reason for skin aging especially early in life because they have a direct impact on the mechanical structure of the skin and I don't talk just about elasticity, "AGEs cause shortened, thinned, and disorganized collagen fibrils"(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965313/). AGEs prevent the collagen fibers from being recycled and those fibers probably accumulate mechanical damage from facial expression that result in wrinkles(didn't saw a study that proved it, this is just my opinion). They also contribute to inflammation and oxidation stress and even partially responsible for the damage caused by sun exposure.

So that cream might not have a drastic impact but it can still have a significant impact because senescent is actually one of the few hallmarks of aging that proved to have a direct impact on skin aging and make the skin thinner.

Posted by: golden axe at October 22nd, 2020 6:20 PM

I'm going to take pictures of both my hands once a week for 12 weeks when I get this, one treated the other untreated and report my results which I estimate will be around February. I am 46 years old.

Posted by: Corbin at October 22nd, 2020 6:25 PM

@Corbin
You are both that would to have asked skin. If using moisturizing ointment and peeling masks you can get pretty decent effects with the regular beauty products.

Posted by: Cuberat at October 22nd, 2020 6:45 PM

@Cuberat
That's a very good point, maybe then just a photo a week after the treatment stops. I don't know anything about beauty products!

Posted by: Corbin at October 22nd, 2020 6:53 PM

@Corbin: Not sure if this is what Cuberat meant too, but you need a placebo on the untreated hand.

Posted by: Barbara T. at October 22nd, 2020 7:01 PM

This has almost no chance of being a senolytic, a substance that actually kills senescent cells. One Skin has never claimed its product to be senolytic. In fact, it claims that "...currently no senolytic is commercially available." At best, OS-01 prevents the accumulation of SEN cells by "support[ing] DNA damage repair" in cells that would otherwise senesce. And we know that's not what a senolytic is for. Also, common skincare products often contain ingredients that may prevent the accumulation of at least some SEN cells by, for instance, blocking UV light or by having anti-inflammatory effects. And curiously, OS-01 contains a bunch of those ingredients, including nicotinamide, besides it's secret sauce known as decapeptide-52.

https://www.oneskin.co/pages/glossary
https://www.oneskin.co/products/os-01

Posted by: Florin at October 22nd, 2020 10:10 PM

Technically Fisetin and or Quercetin/Dasatinib will clear sensescent cells in the body, including skin right ? So I wonder if this product can kill more in the skin. Don't forget the only "local" senolytic treatment (unity) didn't work well. You have to kill them in the whole body, not locally.

Posted by: Jonathan Weaver at October 23rd, 2020 5:07 AM

@Florin
OneSkin hasn't published anything, but in this video (https://youtu.be/0Rem33IdHOM?t=287) they clearly claim to have caused a reduction in the number of senescent cells in skin. Overall, that video is much more thourough than anything on the OneSkin website (maybe they think that good science =/= good marketing?), which gives me hope that this is not snake oil, and perhaps their compound has genuine senolytic properties.

Posted by: gheme at October 23rd, 2020 6:29 AM

@gheme

The chart in that video shows that the senomorphic compounds (stuff that suppresses the production of SASP by SEN cells but doesn't kill SEN cells) One Skin tested also "reduced" SEN cell burden. And, again, the company has never claimed that its product is senolytic and has basically admitted on its own website that it isn't. So, the most likely explanation is that OS-01 might be senomorphic but not senolytic. The claim that OS-01 is senolytic has only been made by people that are not associated with this company.

Posted by: Florin at October 23rd, 2020 2:34 PM

@Florin: I totally agree.
So here's another blow to the credibility of real rejuvenation.
OneSkin's product sounds like one of the dozen "Total DNA repair" skin creams already on your supermarket shelf; or like the "DNA appliance" that supposedly expands the palate of adults through epigenetic nudging (!) Dig deeper and you'll learn that the DNA in the "DNA appliance" stands for Day&Night, not deoxyribonucleic acid.
But alas, people believe these elegantly packaged scams, get inevitably disappointed, and throw the baby out with the bath water.
Then we wonder why there is so much skepticism around.

Posted by: Barbara T. at October 23rd, 2020 3:44 PM

@Florin
In OneSkin's website they say that their product is "preventing the accumulation of senescent cells" and "Decreased Aged Cells"... The website doesn't explain much about how their product work and it sound like they are implying that their product is a senolytic or try to misguide you into thinking that way without directly lying about it.
Can you explain what is the difference between senolytics and senomorphic?.

Posted by: golden axe at October 23rd, 2020 5:56 PM

@Florin
I also didn't saw anything in their website about denying that their product is a senolytic.
So why you think their product isn't a senolytic?.

Posted by: golden axe at October 23rd, 2020 6:16 PM

@golden axe

The answers are in my previous comments.

Posted by: Florin at October 23rd, 2020 7:25 PM

If they had any evidence of their product being a senolytic they would probably have released it as it would be good marketing material. As they haven't it suggests that either (1) they have never really tested their products, they have just assumed that they work. Or (2) that they have tested their products, but found they do stuff all but decided to market and release them anyway.

I wonder how hard it would be to make and test a topical senolytic based on fisetin or dasatinib + quercetin combined with DMSO (di-methyl-sulph-oxide) to get it into the skin?

But as Reason points out most skin aging up to the age of 50 is probably mainly due to other types of damage such as glucosepane sugar crosslinks causing wrinkles or photo damage causing mitochondrial dysfunction. Revel therapeutics might start testing a topical glucosepane breaker in the near future. Maybe the MitoSENS team will one day spin out a topical gene therapy too?

Posted by: jimofoz at October 24th, 2020 5:19 AM

I lost interest at 'proprietary peptide'

Posted by: JohnD at October 24th, 2020 2:53 PM

Hi everyone, Carolina from OneSkin here. We are about to submit our manuscript for publication in a peer-reviewed scientific journal, and in the meantime, we will let it available on a pre-print server. Happy to share it here when it is available. Also, there is a presentation on the ARDD website in which I share more about the data behind OS-1.

Posted by: Carolina reis at October 24th, 2020 5:21 PM

@Carolina reis
So your product is a senolytic or not?

Posted by: golden axe at October 24th, 2020 10:15 PM

@jimofoz
Most of the visible skin aging is probably due to glucosepane regardless if you are before or after 50.
Who said that only after 50 senescent cells start to affect you?. I didn't saw in this blog any study or argument to support this idea other than cancer risk after 50 but that doesn't mean anything because you can't measure senescent cells in the body by risk for cancer. Skin aging have nothing to do with cancer and there are too many different factors behind cancer.

Posted by: golden axe at October 24th, 2020 10:37 PM

@jimofoz
Have actually done Dasatinib + Quercetin in DMSO. Also Fisetin + Azithromycin in DMSO. Two days in a row, once a week (one day Dasatinib+Quercetin, One day Fisetin+Azithromycin). Also at the same time tried to increase NAD+ using: NMN+Apigenin+Rutin+Boswellia in DMSO.
Possible benefits:
Some small reduction in black spots, Possible increase in cheek collagen (skin looks somewhat younger), Possibly some reduction in "turkey neck". Skin looks tighter in the neck area.
Recent young.ai test showed skin age 52 (Chronological age 69), but my face was younger looking before treatment, so not sure to what extent, if any, was the result of the treatment.
Problems:
Skin gets irritated and is very annoying particularly around the eye and the neck, less so at the cheeks. Strong itching around the neck and to some degree at the chin and cheeks. I am not sure if itching is caused by DMSO, or by senolytic action.
I paused temporarily after about 8 weeks until the itching goes away. Even after 10 days, itching did not stop. In the future I am thinking to use dermaroller for penetration that will allow me to replace DMSO with another solvent that is less likely to irritate.

Posted by: Zisos Katsiapis at October 25th, 2020 2:51 AM

@golden axe

We don't have evidence to support a senolytic effect of our peptide. We do see a reduction from 20-50% in the relative percentage of senescent cells, depending on the senescence model we evaluate, without altering cell viability. We are still investigating the mechanism of action, but it is likely to be a combination of increased DNA repair capacity, a decrease of SASP production, and
a regulation of other longevity and senescence pathways leading to a significant decrease of p16 and p21.

Posted by: Carolina reis at October 25th, 2020 6:59 PM

I participated in the free beta test for one skin for 6 weeks. I see no difference but we know of course that collagen takes 3 months to remodel so Ill purchase more.The beta test questionnaire read more like a marketing focus group. I also tried alive by nature, which claims liposomal bioavailable fisetin as a topical senolytic. No noticeable results there either. I've seen modest results with prp injections and IPL lasers. We need to break ages and mostly figure out how to restore dermal fat if we truly want to look younger. And bone health, that's the biggie. The topical senolytic is still quite interesting in terms of being part of an arsenal. I anxiously await one skin's study publication.

Posted by: august33 at October 25th, 2020 10:10 PM

@august33

It does take time to change the makeup of our skin. While some people report improvements as fast as 2-4 weeks, some take up to 3 months. Of course, this will vary from person to person. We also want to reinforce that our main focus is to promote the health of the skin rather than aesthetics aspects. One aspect of skin health OS-01 has been shown to improve is the skin barrier. In a clinical study, OS-01 showed an improvement on average of 15% in the skin barrier, which is related to the main function of the skin of protecting our body against microorganisms infection and water loss.
We appreciate your feedback and please continue to do so.

Posted by: Carolina reis at October 25th, 2020 11:31 PM

Carolina, thanks so much for responding.One thing that I did notice after 3 weeks was less redness, sensitivity, and itching. The base formula is lovely, quite silky and absorbs quickly so I felt that it was a nice non irritating moisturizer. Your comment about it helping to repair the skin barrier makes a lot of sense and I feel that this has happened. That aspect, at least for me, is worth continuing the oneskin product with or without a senolytic effect. I also believe that oneskin had developed some technologies that will allow it to improve and be at the forefront as research continues to rapidly move forward.

Posted by: august33 at October 27th, 2020 10:27 PM

@august33 very glad to hear. Feedback like yours will help us to understand what other indications we can go after and design our next in vitro and clinical studies to confirm the preliminary data we are gathering so far. And yes, the technology and the product will continue to evolve and bring even more benefits to people.

Posted by: Carolina Reis at November 6th, 2020 6:39 PM

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