How to Reverse Skin Aging (2025)

The bigger issue, for me, is that there is such limited amounts of research on peptides from unbiased sources. It still seems like the Wild West…

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Just to chime in a bit on peptide synthesis since I’ve done it in the past. It’s a very well developed field where one can now buy automated synthesizers to do the whole reaction for you. At least for linear and basic branched peptides using the basic 20 amino acids, it’s very straightforward and “easy” to make in the gram to kg scale nowadays. Any impurities as Steve said are likely just unreacted amino acids or other relatively harmless reactants.
As RapAdmin said, though, tox studies are very limited and some of these peptides are quite potent in their effects. My primary concern with some of these are their potential off-target effects, eg I took it to target a specfic receptor but it also targets another receptor in a different tissue.

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I don’t disagree on that :slight_smile:

With skin care, there are well over 80 peptides used in a lot of high end skin care products. One of the great things about peptides is that they are very targeted and typically have short half lives if not modified to increase that. The risk of spill over effects are quite low and adverse reactions don’t last. I think the higher risk is the complexity of many skin care products with 30 to 40 ingredients that are not peptides. The lower the compound count for highly penetrating methods, the better, in my opinion.

With injectables for purposes other than skin care, I’m not terribly concerned about those as they are 1 thing, not a bunch of things like skin care products and the highly targeted aspect remains, as an injectable is generally 1 thing.

Peptides are instruction sheets that only specific receptors can read. Not every cell can read every peptide instruction.

I get questions on this all the time and I explain it like this. Say your body was a building, first under construction, and then being maintained.

Under construction you have multiple trades at work. The master plan requires instructions that are comprehendible to the trade in question and we don’t care if any other trade can read it.
Digging the foundation requires instructions that the plumbing trade can’t read
Framing the building requires instructions the electrician can’t read
Siding the building requires instructions the roofers can’t read

Only the trade that needs to do it’s specific job can read it’s own instructions and all the other trades ignore that.

Same thing happens when the building is finished, sanitary, maintenance, security, IT infrastructure, all get their instructions that are incomprehensible to the other maintainers, so they do not respond.

Our cells are like this, only specific cells can read insulin (a peptide)
only specific cells can read GLP1 (a peptide)
etc.

IMHO, Peptides in general are one of the safest interventions we can do as humans.

So why are there not more RCT studies on the peptide we know and love?

If you can’t make money off the end result, why waste money proving anything about it?

The main problem is how to monetize peptides and the pharma companies have figured out some of that but not all due to the nature of peptide synthesis. If the peptide is bio-identical (humans are a peptide factory making over 7,000) , that is a real problem for getting IP, so it has to be modified to improve it’s performance, as GLP1-RA’s have been created. Even then, because of how peptides are made, they are more easily knocked off.

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That is a good caveat to be aware of. Would this apply to creating a new peptide vs an existing one with known performance?

In my building example above it would be like the plumber reading a new, never before seen instruction meant for the electrician and acting on that with unknown consequences.

Thanks for your posts Steve. I think if I could buy the actual peptide, I would be much more willing to self-experiment. But when I look at the skincare/cosmetic industry as a whole, with all the dodgy claims, misleading studies etc, I just don’t feel comfortable.

For example, there are lots of skincare products with exosomes from various sources, and really none of them have good evidence and they can cause horrendous side effects (including necrosis, permanent scarring etc) after injection.

https://onlinelibrary.wiley.com/doi/10.1002/der2.242

https://onlinelibrary.wiley.com/doi/10.1111/jocd.70520?af=R

https://onlinelibrary.wiley.com/doi/10.1111/jocd.16206

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Not sure what you mean by “actual peptide” the structure of any peptide is perfectly mapped before production. They are easily analyzed to ensure they are what they claim to be.

Exosomes are not peptides they are tiny vesicles (sacs) with a lipid membrane that act as messengers, carrying a complex cargo of proteins, lipids, and RNA to other cells. In contrast, peptides are short chains of amino acids that act as signaling molecules, like “on/off” switches for specific biological processes

Peptides are one thing, amino acids, not a mash up of many things.

Overall bio-identical peptides are incredibly safe and predictable in function.

But it is also easy to make “new” peptides that don’t exist in humans. Modified plant peptides come to mind.

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Thanks Steve. Yeah I do understand the difference between peptides and exosomes. Sorry my post was not very clearly written.

When I say “actual peptide” I mean if I could buy the OneSkin OS-1 peptide in a pure form (like from Sigma, Peprotech etc.) that would be more appealing than bundled into a cream. According to the website, the product contains:

Water (Aqua), Glycerin, Calycophyllum Spruceanum Bark Oleic Extract (Pau Mulato), Sorbitan Olivate, Cetearyl Olivate, Squalane, Carapa Guianensis Seed (Andiroba) Oil, Vitis Vinifera (Grape) Seed Oil, Pentaclethra Macroloba (Pracaxi) Oil, Rosa Canina (Rose hips) Fruit Oil, Prunus Domestica (Plum) Seed Oil, Caprylhydroxamic Acid, Glyceryl Caprylate, Decapeptide-52*, Hyaluronic Acid, Sodium Hyaluronate, Sodium Hyaluronate Crosspolymer, Niacinamide, Allantoin, Bentonite, Tocopheryl Acetate, Tocopherol, Cellulose, Cetyl Palmitate, Sorbitan Palmitate, Xanthan Gum, Potassium Sorbate, Phenoxyethanol, Sorbic Acid, Caprylyl Glycol, Tetrasodium Glutamate Diacetate. *OS-01 Peptide.

So you’ve got a few actives in there like the niacinamide, but also some plant extracts:

Pracaxi Oil. Known for its moisturizing, anti-inflammatory, antioxidant, anti-bacterial, and anti-fungal properties.

Andiroba Oil. A seed oil that promotes healthy collagen and minimizes the effects of inflammation.

Oleic Pau Mulato Extract. An Amazonian tree extract that smooths wrinkles, minimizes skin stress and supports skin healing.

Allantoin. A skin-conditioning molecule that moisturizes and soothes irritated skin.

Hyaluronic Acid. A hydrating acid included in three molecular weights so that it can boost collagen and elastin, support epidermal regeneration, and maintain moisture in every layer of the skin.

And basically, I’m not sure I’d like to also be injecting those things through my skin barrier.

It would also be nice to be able to known, and modify, the dose of OS-1.

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I agree 100% with your concern with the kitchen sink approach used in topical skin care products.

That is why I’m making my own topical for micro needling and DEP.

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Talking about injecting “those things” through skin barrier - yesterday tried Korean serum (approved by AI for DEP) on my face. Today have been having annoying headache since morning and some puffiness under eyes. Coincidence? Could be but I rarely have headaches or puffiness. Won’t try the serum again.

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Keep us posted on what you make and how it goes?

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Hi Lara, I really don’t know, but it’s possible. This a fundamental issue with any sort of cosmetic product. The active ingredient is also accompanied by a bunch of other chemicals to enhance the stability, make the texture nice, maybe also improve the smell or colour. The “serum” products should be simpler with less ingredients, but they still need solubilising agents etc. The products are designed to be well tolerated when applied to the skin. Once you’re pushing it through the epidermis and it has access to the dermis (and thus also blood vessels and systemic circulation), who knows.

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Yes, this. Which is why I much prefer to mix my own when possible. I can control for quality, and I’m willing to re-mix often enough that preservatives are less/not necessary. Can we start a thread for DIY serums?

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Sure - you can start new threads whenever you want!

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I’d be interested in this. Curious where you buy the peptides, and if it’s possible to QC them

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Evidence of oral isotretinoin (Accutane) increasing collagen, but possibly decreasing “elastic fibres”:
“Skin biopsies were performed before and after the end of therapy, and the various sections were submitted to specific staining for collagen and elastic fibres. To analyse the changes, morphometric studies were performed, and the results obtained were analysed by Student’s t-test (paired and non-paired). Clinical results of therapy regarding texture, colouring and aspect of the wrinkles were assessed by both physician and patient. The increase in the amount of collagen fibres was statistically significant with both dosage regimens (mean, 37.8%, increasing to 44.4%; P = 0.029 with the 10-mg dosage; and mean, 36.6%, increasing to 41.9%; P = 0.01 with the 20-mg dosage). A pattern pointing toward a decrease in the number of elastic fibres was found (mean, 15.3-12%; P = 0.014 with the 10-mg dosage; mean, 15.5-14%; P = 0.125 with the 20-mg dosage). Additionally, there was improvement in the general aspect of the skin, regarding texture, wrinkles depth and skin coloration. Despite ethical considerations, a lack of a control group using placebo may render the results less accurate. Low dosages of oral isotretinoin seem to be an effective therapeutic option for cutaneous photoaging.” - Oral isotretinoin in photoaging: Clinical and histopathological evidence of efficacy of an off-label indication https://www.researchgate.net/publication/23276635_Oral_isotretinoin_in_photoaging_Clinical_and_histopathological_evidence_of_efficacy_of_an_off-label_indication#:~:text=Skin%20biopsies%20were%20performed%20before,therapeutic%20option%20for%20cutaneous%20photoaging.

Just don’t do oral tret. Like, never. I don’t understand why folks are like moths to the flame on this one. It’s horrid.

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You mean the skin cream that people use? I’d never do that. But accutane is oral.

Bryan Johnson has used low dose oral Accutane. And for people with terrible skin, it’s an absolute blessing. Yes, it’s basically the nuclear option, but my god it works. I saw my friends daughter go from teenage pizza face to glowing K-pop idol face in a few months using Accutane.

You reap the same benefits with topical tretinoin without inner toxicity. Accutane comes with warnings for birth defects. It’s toxic level of Vit A. I use and abuse 0.1% tret— it’s amazing and $2 / tube.

Reminds me of Dr. Ellie’s take on fluoride: good for topical application to the teeth, but why on earth drink it with your water?

Yes unless someone is plagued by uncontrollable pizza-face acne, zero reason to consider taking it.

Bryan Johnson is a fucking moron. His oral health protocol is also barbaric, and just pats himself on the back based on praise he extorted from some dental hygienist. But dude wears veneers because his teeth are demineralized and I can well understand why. It amazes me anyone takes advice in earnest from him.

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