Does rapamycin improve skin aging?

In a small RCT with 36 participants, topical application of rapamycin reduced the level of a protein that indicates how many 'dormant' senescent cells are present in the skin (P=0.008). At the same time, the amount of collagen VII -- the protein that keeps the boundary layer between the epidermis and dermis firmly in place -- increased (P=0.0077). Several participants also showed a visible improvement in the appearance of their skin^1,2. However, the study lost more than half of its participants along the way. The results are therefore preliminary.

The mechanism behind these effects is biologically plausible. With age, senescent connective-tissue cells accumulate in the skin. These cells release pro-inflammatory substances that damage connective tissue and contribute to wrinkles, skin thinning and sagging³. Rapamycin inhibits a central growth signal in this ageing process. That explanation holds up, but the step towards proven benefit in humans has not yet been taken.

In a laboratory study using cultured human hair follicles, rapamycin stimulated hair growth and pigment production, even in grey follicles that still contained living pigment cells⁴. This is interesting for research into hair loss and greying, but these are laboratory results. What this does in people in everyday life remains unknown.

On safety: rapamycin taken as a pill or infusion reduces immune defences and can impair wound healing. In the small RCT using topical application, no serious side effects occurred, but the study was too small and too short to assess this properly^2,5. Commentary pieces emphasise that there are still considerable hurdles to clear before this therapy can be widely used. Until those questions are answered, self-directed topical use of rapamycin is premature.