It seems like the evidence for significant benefits of topical rapamycin (i.e. rapamycin skin cream) gets stronger and stronger every year. There are now two companies that are developing topical skin creams using mTOR inhibitors for skin aging:
Hayflick Partners (Matt Kaeberlein is on the advisory board): https://www.hayflickpartners.com , and they mentioned in the recent podcast that this company was developing a topical version of rapamycin.
and many here have been using topical rapamycin for a long time using this protocol: DIY Rapamycin skin cream
Omipalisib
I also realized when listening to this recent podcast interview with Ben Blue of Ora Biomedical that they’ve had great results with the mTOR inhibitor Omipalisib (GSK2126458), and have now standardized using it as a positive control in all their experiments because it much better than rapamycin.
It seems like it would be quite easy and low risk to swap out the rapamycin in the DIY Topical skin cream, for the Omipalisib (GSK2126458), assuming you can actually get your hands on Omipalisib (its available from many lab supply companies, but that doesn’t mean its easy to get). In earlier rapamycin skin cream research it was shown that the rapamycin does not enter the blood stream when applied topically (so systemic risks are minimal).
Just wanted to share something that’s been working well for me in case it helps someone else. I’ve been using diluted Radiesse (both 1:0.5 and 1:1 ratios) over the past 6 mo—not for volume, but more for skin quality and subtle structure. I wasn’t expecting anything dramatic, just wanted to soften some of the signs of aging.
Well, I ran my photo through that Face Age AI tool out of curiosity, and it came back with a facial age of 35. I’m 70. I know those tools aren’t perfect, but still—it was a nice moment.
There are so many approaches to facial rejuvenation these days like mTOR inhibitors and other longevity pathways that may help over time, which I think is fascinating. I’m impatient and want the results now vs tomorrow. If you’re looking for something with more immediate, visible results, I’ve found that diluted Radiesse can be a great option—especially when done conservatively.
Not claiming it’s a miracle, just sharing what’s worked for me. It gave a kind of “soft filter” effect that looked natural and didn’t scream “filler.” I can post or dm my pic if somebody is interested.
New trial results : Oral sodium hyaluronate improves skin hydration, barrier function and signs of aging. Seems like a convenient way to do skincare: just use a pill. The highest dose of 120mg had better results.
According it AI, many researchers currently recommend a “balanced” weight (300–500 kDa) for the best absorption and skin-plumping results. The higher molecular wight ones come with their own benefits like knee pain and joint stiffness relief.
I still like rapamycin cream.
I recently changed my rapamycin cream formula. Mainly, I did this to make it easier. The essential part is to dissolve crushed rapamycin in Trancutol, then filter it and add it to a base cream. The base cream I am currently using is SimplyVital Anti-Aging Face Moisturizer with Retinol, Collagen & Hyaluronic Acid. I get it from Amazon.
This was based on a recommendation from ChatCPT 5.2
Example Workflow (Using the products above)
Rapamycin stock solution: dissolve rapamycin (e.g., 12.5–25 mg) in Transcutol (~2–3 mL) with gentle stirring.
Prepare base: weigh out 30–50 g of your chosen cosmetic base.
Mix: slowly add the rapamycin/Transcutol solution into the base while stirring thoroughly.
Pack & label: into an opaque airless jar or pump.
Test: small patch on the forearm/neck before face use.
I have been using this for about a month. It really seems to produce a clear skin and, so far, no new actinic keratoses.
In the topical rapamycin studies it was used daily - so frequency of use is different from typical oral once a week use. I also imagine skin deposition is not large from relative small oral doses - skin is a large organ. With topical you can concentrate the drug on specific areas like the face or neck.
Pentagalloyl glucose (PGG), a polyphenolic molecule with high affinity for elastin hydrophobic domains, binds non-covalently to exposed elastin, shielding cleavage-prone motifs, reducing water ingress into hydrophobic repeats, and sterically limiting protease access [147]. In multiple AAA models, PGG has preserved elastic lamellae, reduced inflammatory infiltration, and slowed or prevented sac expansion. [94,148]. Localized periadventitial delivery of non-cytotoxic PGG early after injury inhibits elastin degeneration and attenuates AAA growth, indicating that targeted wall exposure can modify disease trajectory even without systemic drug levels [94]. Extending this concept, PGG-loaded nanoparticles have been engineered to home to the aneurysmal wall, where controlled release restores degraded elastin ultrastructure, reduces MMP activity, and diminishes leukocyte infiltration. Notably, oral administration of PGG nanoparticles has regressed established elastase-induced AAAs in preclinical studies, suggesting that systemic routes can achieve therapeutically meaningful aortic exposure when coupled with appropriate carriers [149]. Mechanistically, PGG effects likely arise from a triad: (i) direct fiber stabilization which reduces elastase susceptibility, (ii) secondary anti-inflammatory actions, i.e., less Damage-Associated Molecular Patterns release from matrix breakdown due to lower cytokine/MMP induction, and (iii) favorable reparative remodeling by providing a protected scaffold onto which new matrix can organize [117,118,119,120]. While PGG is an example, this “elastin-tanning” principle may extend to other elastin-binding polyphenols, tailoring small molecules with improved pharmacokinetics and tissue selectivity.
In a career that has spanned 30 years, Dr. Vyavahare’s research has been focused on elastin, a rubber band-like protein dominant in the the tissues of our lungs, arteries and skin that allows these organs to expand and retract. The body’s ability to repair elastin diminishes with age and the loss of elastin is accelerated by oxidation, inflammation and pollutants that cause tissues to lose elasticity. Through his research, Dr. Vyavahare discovered that a specific antioxidant called PGG would bind to elastin and support its maintenence. Taking it a step further, he paired the PGG with a novel micro-hyaluronic delivery system which would allow cells to support new elastic fiber and strengthen the tissue. The discovery has been patented and is now being used to repair lung tissue in patients with COPD, restore damaged arteries and repair damaged skin.
