How to Reverse Skin Aging

#976

Perhaps verteporfin+microneedling (or other therapy that stimulates wound healing like laser treatment) could rejuvenate elastin. Some hair transplant surgeons have already been using verteporfin as it shows some ability to regenerate excised hair follicles, in addition to reducing scarring.

The Longaker lab at Stanford has done much of the work on how verteporfin prevents scarring. If you have time, great recent lecture (with health implications for more than just skin regeneration):

In pigs (which have skin closer to humans) verteporfin can normalize the elastic ratio in response to a wound, which suggests that it regenerates elastin (which normally is poorly regenerated in adult wound healing [ref]).

Screenshot 2025-01-03 at 10.46.53 PM

Data from Elucidating the Role of Tissue Mechanics in Wound Repair and Regeneration (PhD thesis)

Verteporfin is already an approved photosensitizing drug (it generates ROS in response to certain light frequencies) for macular degeneration, but in wound healing it acts by inhibiting the YAP pathway. This prevents Engrailed-1+ fibroblast conversion, which would otherwise promote a scarring/fibrotic response.

Also of note, ELNs promoter is structured like a housekeeping gene [ref] (these are constitutively expressed genesā€”e.g the glycolytic enzyme GAPDHā€”that are necessary for basic cellular life, regardless of cell type), and it seems that the drop-off in tropoelastin synthesis during adulthood is due to post-transcriptional regulation. In particular, RNA interference from the miR29 family of micro RNAā€™s seems to play an important role, and miR29 antagonism can raise tropoelastin protein levels in adult human dermal fibroblasts, relative to controls. [ref].

Itā€™s worth mentioning TGF-Ī², which is the ā€˜master regulatorā€™ of fibrosis, and that miR29 family downregulation is a hallmark of TGF-Ī² signaling, where it acts to increase translation of extracellular matrix proteins. [ref] So although miR29 antagonism might upregulate tropoelastin synthesis, by promoting collagen synthesis it would be expected to drive a fibrotic phenotype.

Not that you would want to upregulate TGF-Ī² anyways, as its primary transcriptional response is the pro-aging cytokine IL-11, which (at least in certain tissues) is necessary for the TGF-Ī²-mediated fibrotic response. [ref] Iā€™m working on a separate post to highlight the fact that rapamycin activates TGF-Ī² signaling, and that this very well might cap any associated increase in health/lifespan, especially with high doses and/or non-intermittent usage.

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#977

Possible is a good starting position.

Now we need to know how localized this effect is and it seems to be highly localized, so not yet helpful in longevity.

Next question would be how to make it systemically effective if it is actually an elastin rejuvenator.

Now Iā€™ve got to get me some hydroxylapatite to play with.

I have used CaHa toothpaste but the evidence is quite low for a real benefit that does not seem to match the hype in this application.

1 Like
#978

And this is one of the reasons the production of elastin has to stop.

The other reason is the 70 year half-life

#979

Radiesse is FDA-approved specifically for improving the contour of the jawline. This treatment helps to add definition and volume, enhancing the overall appearance of the jawline.

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#980

This is a new product that looks pretty good, including published data. Saw it at the A4M conference last month. We have some on the way. Itā€™s a bit pricey, but we get a decent discount.

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#981

Another approach would be to lengthen the half-life (which of course is a function of degradation rate).

Healthy living (and some of the supplements and drugs taken here) might do this by reducing oxidative stress and lowering glucose (and fructose) levels within the extracellular matrix. This would reduce oxidative and glycative insults to elastin, lengthening its functional half-life.

Another possibility is to modulate enzymatic breakdown of elastin by inhibiting the elastases, MMPs, and cathepsins that can degrade it.

Sivelestat is a neutrophil elastase inhibitor approved for acute respiratory distress, and preliminary reports suggest efficacy in treating neuropathic pain(!) Some flavonoids like quercetin also inhibit neutrophil elastase, although whether the IC50 is low enough for clinically relevant inhibition I havenā€™t looked into.

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#982

MMP inhibitors seem promising. Low dose doxy/MINO and/or low dose oral isotretinoin could help in theory.

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#983

That looks interesting! Would love you to compare it to what Iā€™m currently using.

They seem similar-ish? Also pricey, but I do get mine on sale.

Ingredients:
Human Umbilical Mesenchymal Stem Cell Conditioned Media, Water (Aqua), Glycerin, Aloe Barbadensis Leaf Juice, Sodium Hyaluronate, Niacinamide, Panthenol, Magnesium Ascorbyl Phosphate, Ascorbyl Glucoside, Sodium Ascorbyl Phosphate, Hydroxyethylcellulose, Caesalpinia Spinosa Gum, Bis(tripeptide-1) Copper Acetate, Polysorbate 20, Polysorbate 60, Ceramide NP, Ceramide AP, Ceramide EOP, Acetyl Octapeptide-3, Palmitoyl Tripeptide-37, Palmitoyl Tripeptide-1, Palmitoyl Tetrapeptide-7, Acetyl Hexapeptide-8, Trifluoroacetyl Tripeptide-2, Dextran, Tetrahexyldecyl Ascorbate, Pullulan, Arginine, Glutathione, Yeast Extract, Nannochloropsis Oculata Extract, Camellia Sinensis Leaf Extract, Citrullus lanatus (Watermelon) Fruit Extract, Pyrus Malus (Apple) Fruit Extract, Lens Esculenta (Lentil) Fruit Extract, Sodium PCA, Sodium Lactate, Sodium Phytate, Leuconostoc/Radish Root Ferment Filtrate, Caprylyl Glycol, Ethylhexylglycerin, Phytosphingosine, Cholesterol, Sodium Lauroyl Lactylate, Carbomer, Xanthan gum, Phenoxyethanol, Hexylene Glycol, Butylene Glycol, Disodium Phosphate, Sodium Phosphate, Sodium Benzoate, Potassium Sorbate

KLOTHO SKIN
Water (aqua), Human Neonatal Fibroblast Conditioned Media, Human Adipose Stromal Cell Conditioned Media, Glycerin, Butyrospermum Parkii (Shea Butter), Squalane, Niacinamide, Panthenol (Vitamin B5), Aloe Barbadensis Leaf Juice, Lecithin, Sodium Hyaluronate, Tetrahexyldecyl Ascorbate, Chondrus Crispus Extract, Caprylic/Capric Triglyceride, Teprenone, Sambucus Nigra (Elderberry) Fruit Extract, Lycium Barbarum (Goji) Fruit Extract, Malus Domestica Fruit Cell Culture Extract, Xanthan Gum, Carbomer, Ammonium Acryloyldimethyltaurate/VP Copolymer, Ethyl Lauroyl Arginate HCl, Tocopherol, Phenoxyethanol, Caprylyl Glycol, Potassium Sorbate, Citric Acid, Citrus Aurantium Dulcis (Orange) Peel Oil.

2 Likes
#984

$250 for a facial serum? Is it backed up by research and trials? :blush:

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#985

They have some studies listed on their website, as you scroll down.

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#986

The Cleveland Clinic talks about Jojoba oil and skin health.

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#987

Has anyone tried thisā€¦ sunscreen in pill form? (or just take similar ingredients)

The science:

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#988

The only thing in there that may somewhat work is astaxanthin and only at higher doses (12mg+).

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#989

Sounds like pseduoscience, put bunch of ingredients that my have some remote effect on the skin (ā€œthe scienceā€), throw it at the wall and see what sticks.

Until they have DBPC trial of their actual concoction, itā€™s all just speculations - sort of what we are doing for longevity.

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#990

Yes - this is the fundamental problem I have with supplement companies more generallyā€¦ lots of hype over small effect sizes or minimal data sets. They are mostly just marketing companies.

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#991

Which shows you how easy is to create a product based on pseudoscience.

Technically, anyone here could create stack for longevity for sale and have AI comb this forum alone for ā€œscientificā€ explanation for each ingredient and links to studies why it would work.

That summarizes the whole supplement industry: you can literally sell dehydrated dog poo if can market it well enough.

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#992

Polypodium seems to have some evidence of protection from UV rays. Other ingredients are more just general skin health.

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#993

Yes, polypodium leucotomus, aka ā€˜Fern blockā€™, is a consolidated supplements which is supposed to protect the skin (at dosages maybe higher than 250 mg/d). Now, the protection is relative to many factors, but this and astaxanthin (again, the dosage seems low) seem to be the two specific skin protectors. Collagen and hyaluronic acid seem to be 2 well-known protective or regenerative ingredients. Niacinamide also targets the skin reaction to light rays.

Bottom line, that seems to be a legit supplement, although the dosages might be varied.

Last summer I tried polypodium 500 mg + astaxanthin 8 mg + B3 50 mg, with no apparent effect on my intolerance to strong solar radiation. Just a n=1 anedocte. Iā€™ll try again next year, starting maybe in March.

1 Like
#994

SKINCARE. Prompted by this thread, Iā€™ve started to tackle this topic and the first impression is probably the feeling I would have landing on an alien planet. I donā€™t know if other forum users share the same experience.

On the other side, this constitutes a good cognitive challenge. The approach should be based, as done in other fields, on some basic rules: discriminate the sources, try to grab the governing principles, try to adapt the rules to your individual genetic makeup and situation. And there is some fun in the discovery, trying to develop a personalized skincare routine, trying to optimize products, costs and time. Itā€™s sort of a game and Iā€™m starting to enjoy it.

I found a good source in the book of Victoria fu and gloria Wu, the chemists previously suggested by Admin. Decoding Skincare. Pretty good basic book on basic principles by competent authors with no conflicts of interest.

It seems that the book has been presently expanded in a 2nd edition, I missed it by a few days. But it is not available everywhere.

Another source I found useful is some podcasts from aesthetic surgeons and dermatologists. Reliability must be judged. There are sometimes blatant conflicts of interest, but these are often separated from the principles they expound.

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#995

Another interesting thing to think about is the healthy skin microbiome. An esthetician friend of mine has been harping on me to reduce using creams that have lots of preservatives as it can be disruptive to sensitive skinā€™s microbiome (I have a bit of rosacea). So I stumbled on this study today:

I wonder if weā€™ll start seeing probiotic products for skin a lot more going forward.