How to Reverse Skin Aging (2025)

#543

Hey man his heart is in the right place, until gene therapies relocate it.

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#544

I was in the UK trials for isotretinoin in about 1980. Was incredible result for my acne.

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#545

Sorry, to clarify, I wasn’t saying Bryan is doing everything right or that we should copy him. That part was in response to your “I don’t understand why folks…” statement.

I do agree that it’s a harsh drug, and I wouldn’t use it for anti-aging myself.

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#546

His heart maybe. His head definitely not.

#547

And what were the results?

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#548

Considering doing a low dose isotretinoin for a while for anti-aging effects on skin. Maybe 5mg a night.

Oral isotretinoin as part of the treatment of cutaneous aging

“All patients treated with oral isotretinoin noted improvement in wrinkles, thickness and color of the skin, size of pores, skin elasticity, tone, and reduction in pigmented lesions and mottled hyperpigmentation. A statistically significant difference was found in the improvement of group A (Wilcoxon test <0.01). Using minimal amounts of this drug, the side effects were practically negligible.”

Oral isotretinoin in photoaging: objective histological evidence of efficacy and durability

“According to histological analysis, 65% of the patients revealed alteration in the distribution and thickness of the elastic fibers, which can be interpreted as a histological improvement, while 60% showed an increase in collagen density. We observed an increase in collagen density, from 51.2% to 57.4%, (p=0.004). At the end of the 12-week follow-up period, this density decreased to 54.7% (p=0.050). There was an increase in the density of elastic fibers, from 26.5% to 31.3%, (p=0.02), which had dropped to 27.5% at the end of the 12-week follow-up period.”

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#549

A post was split to a new topic: Pterostilbene-based anti-aging cream greatly improved skin firmness, elasticity, and wrinkle reduction

#550

Topical estrogen and estriol creams for treatment of skin aging:

“After treatment for 6 months, elasticity and firmness of the skin had markedly improved and the wrinkle depth and pore sizes had decreased by 61 to 100% in both groups. Furthermore, skin moisture had increased and the measurement of wrinkles using skin profilometry, revealed significant, or even highly significant, decreases of wrinkle depth in the estradiol and the estriol groups, respectively. On immunohistochemistry, significant increases of Type III collagen labeling were combined with increased numbers of collagen fibers at the end of the treatment period. As to hormone levels, only those of PRL had increased significantly and no systemic hormonal side effects were noted.”

Treatment of skin aging with topical estrogens Treatment of skin aging with topical estrogens - PubMed

#551

Thats interesting, but an old paper (almost 30 years old), from 1996. I put this into CGPT:

review all human-skin studies (1996–2025) testing topical estrogens / SERMs / phytoestrogens for anti-aging, summarise efficacy vs risk, and estimate suitability for a longevity-oriented skin-care regimen.

Summary of response:

Where the field is, 2025: critical synthesis

Evidence strength

  • Classical topical estrogens
    • Mechanistic: strong (collagen up in sun-protected skin).
    • Clinical facial/photoaged benefit: inconsistent and modest; best modern trials show no meaningful effect on wrinkles/elasticity and possible MMP-1 upregulation.
    • Safety: unknown long-term; no serious events reported, but underpowered.
  • MEP (soft estrogen)
    • Mechanistic: plausible local ER activation with in-skin deactivation.
    • Clinical: one decent pilot RCT with favorable results on dryness/laxity/atrophy.
    • Safety: short-term looks clean; no systemic hormone changes reported; long-term unknown.
  • Topical phytoestrogens
    • Mechanistic: ERβ-biased, antioxidant, anti-inflammatory; animal/preclinical data strong.
    • Clinical: small RCTs show mild improvements in hydration, roughness, fine lines; weaker histologic changes than estradiol.
    • Safety: good short-term tolerability; systemic impact minimal at tested doses.

Major knowledge gaps / debates

  • Photoaged vs protected skin: Rittié and Yoon essentially argue that chronic UV-damaged facial skin is “estrogen-resistant” for collagen induction and may even respond adversely via MMP-1. This directly contradicts the marketing narrative that estrogen face creams “reverse” facial sagging.
  • Cancer risk: No trial is big or long enough to address keratinocyte carcinoma, melanoma, or breast cancer risk from repeated facial estrogen application over years.
  • Sex and age: Most data are peri/postmenopausal women; male skin and significantly older (80+), or very early menopause, are poorly studied.
  • SERMs proper (raloxifene, bazedoxifene) as topicals: essentially no human facial-skin data; current “SERM-like” in this space are mostly phytoestrogens rather than pharmaceutical SERMs.

7. Practical implications for a longevity-oriented regimen

7.1 What not to do (on current evidence)

  • Treat classical estrogen face creams (estradiol/estriol/oestrone) as a primary anti-aging solution for photoaged facial skin. The better-designed modern trials fail to show robust benefit and raise concerns about matrix degradation via MMP-1.
  • Assume they are “safe” long-term; the absence of evidence is not evidence of absence here.

7.2 Reasonable experimental tools (with caution)

If someone insisted on estrogenic modulation for skin, the more rational, hierarchy-aware approach would be:

  1. Standard, non-estrogenic mainstays first
  • Topical retinoids (tretinoin / retinaldehyde), AHAs/BHAs, niacinamide, UV protection, plus procedures (resurfacing, microneedling, RF, etc.) all have far stronger evidence for wrinkle reduction and dermal remodeling than any estrogenic cream. Estrogens, if used at all, should sit on top of an optimized base, not instead of it.
  1. Topical phytoestrogens as low-risk adjuncts
  • A genistein- or mixed-isoflavone cream aimed at ERβ, with robust moisturizing vehicle, is probably the best “first stop” estrogenic adjunct: modest effect sizes, benign safety profile so far.
  • Mechanistically appealing for scalp/follicle as well (ERβ-rich), though hard endpoints are sparse.
  1. Soft estrogen (MEP) only in tightly controlled n=1
  • If you have access to MEP formulations, they are conceptually superior to full ER agonists, but human data are thin. Any self-experiment should track: high-res imaging, skin biomechanics (if available), and ideally systemic sex-steroid panels at baseline vs 3–6 months.
  1. Systemic support via oral phytoestrogens (if no contraindication)
  • Soy isoflavone or equol-based supplements show small but consistent improvements in facial wrinkles/hydration in postmenopausal women and may also benefit bone and metabolic health, without the risk profile of systemic ERT.
  • These are more defensible longevity tools than smearing full estrogen on the face.
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#552

RapAdmin,

In connection with the use of hormones to reverse skin aging I asked chatGPT to research the types used in medical studies. The report did not include the need for blood tests to check for changes in hormone levels from systemic absorption, but that would be important. Here is the result:

Most common estrogen type(s) used + dosing / formulation

Across the studies and reviews:

Estrogen Type Typical Concentration / Dose / Regimen
17β‑Estradiol 0.01% cream / ointment — used daily or multiple times per week, often for 6 months. PubMed+2ScienceDirect+2
Estriol 0.3% cream — used in some studies alongside estradiol (same 6‑month protocol) for skin‑aging in perimenopausal women. PubMed+2PubMed+2
Methyl‑estradiolpropanoate (MEP) (an “estrogen‑like” soft‑drug) Applied topically (face) twice daily for ~14 weeks — pilot trial in postmenopausal women. JDD Online

Formulations: Mainly creams or gels, sometimes under occlusion (especially in early mechanistic studies), sometimes applied to buttock, hip, or less sun‑exposed skin (to reduce confounding by photodamage). PubMed+2ScienceDirect+2

Duration: Beneficial changes mostly reported after weeks to months (e.g., 8 weeks, 16 weeks, 24 weeks, or 6 months). PubMed+3PubMed+3PubMed+3

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#553

Just started 10 mg/d to clear up my face some more since I’ve been getting more frequent breakouts.

Planning to do 6-12 months and then transition to a “maintenance dose” of 5 mg a day or EOD.

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#554

Do you also use topical retinoids?

#555

Tried the lowest strength tretinoin and tazarotene on and off. My skin is too sensitive to them… I can tolerate the tazarotene lotion (Arazlo) though, but it’s not available as a generic.

#556

What dose are you thinking about?

I’ve had 5 boxes of 10 mg isotretinoin sitting at home since last year and still can’t bring myself to start a low-dose regimen. I’ve done a lot of reading, and it really might do wonders for skin at low doses, but I just can’t justify the risk for myself.

I really don’t see how low-dose isotretinoin could be beneficial for longevity. There are some hints it may help at the cellular level in certain ways, but overall it seems net negative long term.

For context, I’ve been using 0.05% topical tretinoin for 15+ years and my skin (in terms of aging) looks more or less the same as when I started. So I’m wondering: why would you consider oral isotretinoin? What’s your reasoning behind it?

I see a lot of Gen Z taking low-dose iso for “porcelain skin” and prevention… but is it really worth it in the long run? And if you’re using it as an anti-aging strategy, wouldn’t you need to stay on it continuously?

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#557

I ended up changing my mind. I’m just going to use topical retinoids. I keep seeing compelling evidence for low dose oral isotretinoin but then I see a lot of negative health effects long term. Why add another complication?

To answer the question of what dose I was thinking about it would have been 5-10mg a night.

I’ve got a lot of topical things to try out: microsphere tretinoin, tazarotene, estriol and estrogen creams. I also just recently purchased the Derminator 2 microneedle device. I’ve not used it yet, I’m waiting until I have a few days off work and any social obligations before I use it just in case it looks kind of brutal.

With all of this, why would I even need oral isotretinoin?

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#558

@PrimarchLongevity I always found a lot of sensitivity with tubes of tret, but then I tried Dermatica and then Curology tret. There is something about their formulas that are much less sensitizing for me. If you wanted to try them, they usually offer great intro deals… if you can’t find one, I’ll look up my discount code for you, but I don’t think you’ll need it.

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#559

I’ve posted about the potential of facial fat loss from devices, so I’m sharing a video from insta by a respected plastic surgeon on the topic.

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#560

Another new company doing a topical Rapamycin-type cream for prevention of skin aging:

in addition to this earlier announcement: A New Rapalog for Skin Aging: Rapalogix Health RLX-201

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#561

My simple tips for better skin:

  • Vitamin supplements (esp C, D, E). You should probably take these anyway, but yes, it’s also beneficial for the skin.
  • Topical vitamins, i.e., ascorbic acid (C) and niacinamide (B3). I use only serums and don’t bother with all the fancy pants brand creams you can get. For both I use 10% concentrations. If you can get higher, fine, but this is what’s readily available to me and it barely costs me anything. For vit C, I just use the stablised form. Much easier to deal with and honestly I think it works fine. But if you can get the pure form ( L-ascorbic acid), that should be better in theory, but don’t worry about it too much.
  • Hyaluronic acid, another serum. I use 2% and I combine this with the other products all the time for better absorption and just better hydration. Again, go for the basic cheap serum, not the fancy stuff.
  • Retinoids, of course. Tretinoin or Tazarotene. If your skin can’t handle it, at least try Adapalene. Start with a lower strength (e.g., 0.025) and optionally increase it over time (0.05, 0.1). Retinols are pretty much a waste of time and money, so I don’t even bother with those.
  • Azelaic acid. It is important it is at least 15% (personally I use 20%). Great product to add for soft and evenly toned skin.
  • Hydroquinone. This is a great product that addresses imperfections like sunspots. Only thing is, you shouldn’t use it too often. Personally, I use only one tube (4%, 30g) per year. Just use it daily, and when you run out, wait a year or so.
  • SPF, basic stuff, just use it even if it’s not very sunny.

Personally, I have strong skin and it’s been ‘retinised’ by now, so I don’t really have to worry about much, but at first you will have to get used to it and will peel a bit. And don’t combine everything at first. I use .05% tretinoin, mix it with some azelaic acid and moisturiser, then apply it to a damp face with hyaluronic acid already applied. This I do every night without issue (use a cleanser beforehand if you didn’t just shower). In the mornings, I alternate between vit c and niacinamide, together with hyalurinic acid and, again, moisturiser.

Any stuff that is not otc, I just buy online. Why even deal with Rx and all that just to still end up paying more? These are basic ingredients that cost pennies to produce and are easy to buy online nowadays.

Hope this helps anyone. I am a guy and when you look into this sort of stuff you quickly find we are generally leaps behind women in this domain, but I’m trying to catch up a bit. At first I was skeptical b/c my view was it was all marketing bs. And basically, it turns out that most of it is. But there are some things that truly work and if you stick with those, you can get good results.

Also, I wanted to share with you this trial I came across:
Phase 1 Study of KB304 for Moderate to Severe Wrinkles

Looks promising. The start of this thread discussed how there is loss of elastin in the body over time (and no reproduction). This study seeks to address that. The results may also be found as a pdf here.

AI Summary of linked article

Jeune Aesthetics announced positive Phase 1 results from the PEARL-2 trial of KB304, an investigational injectable gene therapy for moderate to severe décolleté wrinkles. The randomized, double-blind, placebo-controlled study showed statistically and clinically meaningful improvements in skin appearance and quality, favoring KB304 over placebo.

Key findings

  • Efficacy:
    • Investigator-rated GAIS showed 100% of KB304-treated subjects achieved at least a one-point improvement in wrinkles at 1, 2, and 3 months, versus 14–28.6% with placebo.
    • Subject-rated GAIS similarly favored KB304, with 72.7–90.9% reporting improvement across timepoints (vs 14.3% placebo).
    • 81.8% of KB304 recipients reported improved satisfaction with wrinkles at 3 months (SSQ), compared with 14.3% on placebo.
  • Broader skin benefits: Investigators reported universal (100%) improvements in elasticity, crepiness, hydration, and radiance among KB304-treated subjects at all assessed timepoints.
  • Safety: The safety profile was favorable , with mostly mild-to-moderate adverse events that diminished after initial dosing; no severe or drug-related serious adverse events occurred.

Study details

  • Participants: 19 enrolled (12 KB304, 7 placebo); 18 completed assessments.
  • Mechanism: KB304 uses a non-integrating HSV-1–based vector to deliver genes encoding type III collagen (COL3) and elastin, aiming to restore the extracellular matrix by inducing endogenous production in skin cells.

Next steps

  • Based on the results, Jeune plans to advance KB304 to Phase 2, meet with the FDA, and submit a newly developed décolleté-specific wrinkle scale (JDWS). Phase 2 initiation is targeted for first half of 2026.

Significance

  • KB304 is positioned as a first-in-class approach that directly addresses elastin (and collagen) loss and targets the décolleté, an area with no FDA-approved injectable treatments, aiming for natural-looking rejuvenation.
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#562

KB304 looks very promising.