Does rapamycin improve skin aging?

A small exploratory RCT with 36 participants¹ shows that topically applied rapamycin favourably influenced two biological ageing markers in the skin. The level of p16INK4A, a protein that indicates how many 'dormant' (senescent) cells are present in the skin, fell significantly (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). Both findings point in the right direction, but the study lost more than half of its participants during the research period, which means the results are preliminary and should be interpreted with caution.

In addition to the biological markers, a clinically visible improvement in skin appearance was also reported in several participants, supported by histological examination^1,2. These are encouraging signs, but not hard evidence that rapamycin actually reverses skin ageing. The study was too small and too short for that, and the clinical assessment was not blinded.

The mechanism behind the effects is biologically plausible. In the dermis, ageing connective-tissue cells accumulate over time and secrete pro-inflammatory substances, the so-called SASP (senescence-associated secretory phenotype). This disrupts connective-tissue maintenance and contributes to wrinkles, skin thinning and sagging³. Rapamycin inhibits the mTOR signalling system, which plays a central role in this ageing process. That mechanistic story is consistent, but the translation to proven clinical benefit in humans has not yet been made.

In a laboratory model using cultured human hair follicles, rapamycin stimulated hair growth and pigment production via mTOR inhibition, including in grey hair follicles that still contained living pigment cells⁴. This is interesting for applications in hair loss and greying, but it is exclusively laboratory research. Effects in humans in everyday life have not been demonstrated by this.

On the subject of safety, the following can be said. Systemic use of rapamycin, that is, as a pill or infusion, carries well-known risks such as reduced immunity and impaired wound healing. In the small RCT with topical use, no serious adverse effects were reported, but the study was too small and too short to answer safety questions adequately^2,5. A commentary piece emphasises that there are still considerable hurdles before this type of therapy can be widely used in clinical practice. Until those questions have been answered, topical rapamycin outside a study setting is not yet ready for independent use.