Topical Rapamycin (Sirolimus) for Skin Senescence

We did a review of the data on topical rapamycin to target skin senescence. Here are the key takeaways:

Key Takeaways and Underlying Mechanisms of Topical Rapamycin Works

1. Rapamycin reduces the total amount of senescent cells

The data suggests that the improvement observed may be due to the reduction of the overall burden of senescent cells. This could be due to rapamycin reducing the pro-inflammatory secretions produced by senescent cells, or it could be that rapamycin is reducing the number of senescent cells.

The fact that p16 is reduced suggests that the absolute number of senescent cells in the epidermis is reduced.

Rather than simply modifying senescent cells present in the tissue, rapamycin treatment either reduces the number of cells entering senescence or increases the clearance of senescent cells.

Whether the reduction in senescent cells is due to reduced entry into senescence or increased clearance, a reduction in the burden of senescent cells would be expected to improve functionality. Beyond skin health, the implication of these results suggests that rapamycin could be a powerful tool to reduce senescence throughout the body.

2. Reduction in the SASP and inflammatory cytokines

Senescent cells produce substances called pro-inflammatory cytokines, matrix metalloproteins, and reduced levels of anti-angiogenic factors, which together create an environment that can support tumor growth and negatively affect stem cells. This group of substances is known as the Senescence-Associated Secretory Phenotype (SASP). In normal cells and tissues, the SASP is closely linked to the expression of the p16INK4A protein. The results of the study suggest that rapamycin reduces inflammatory cytokines in the skin.

3. An increase in collagen, and autophagy of misfolded collagen

Rapamycin seems to improve the incorporation of collagen VII into the basement membrane of skin, which is a measure of skin quality. Collagen VII is important for maintaining a functional skin barrier, but its levels decrease with age and in areas where wrinkles form.

The mechanism by which rapamycin increases collagen VII protein levels is not fully understood, but it is thought that rapamycin’s effects on autophagy and vesicle trafficking may allow for the proper processing and localization of collagen at the cell periphery and basement membrane.

Collagen VII has also been linked to the clearance of misfolded proteins and extracellular pathogens, and may play a role in maintaining cell-cell junctional integrity.

If you put rapamycin onto a small area of the face eg half a cheek, would it work only on that area? Or would it absorb into the skin and affect the whole face? Thank you.

what about applying rapa cream to fresh surgical scars on the face?

That would probably be a bad idea. Rapamycin is known for slow wound healing. You probably need the inflammatory process to heal the surgical wounds.

Agree… I guess it could help with scarring. But if the wound gets infected, I think scarring would be inevitable anyway. Lol

One question - I recently read the hand study on topical rapa that is the primary evidence for rapa stopping skin aging. But they use .001% rapa. They say that they think that lower concentration of rapa would balance its positive effects of stopping senescent cells, yet still allowing for growth. They say higher concentrations may inhibit growth. Just started the cream from you guys. Seems nice, but it’s .2%. Any worries it could inhibit growth and actually cause skin thinning??

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Hello! This is Shriya from the Healthspan Clinical Team. Our advising physicians have chosen the 0.2% concentration based on a clinical trial that evaluated the safety and efficacy of topical rapamycin for senescence. This particular dose was found to offer the most beneficial effects while minimizing side effects. It’s important to note that while other studies might use a lower percentage, the frequency and quantity of their administration could vary. This can affect the overall impact and results of the treatment. If you have more questions about Topical Rapamycin please let us know.

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what about for AGA hair loss how is it applied and how often?