RLX-201, a Novel mTORC1 Inhibitor With Potential to Promote Skin Longevity and Cellular Health.

mTORC1 activity drives characteristic phenotypes of senescence, contributing to extracellular matrix breakdown and accelerate aging phenotypes. Targeting mTORC1 without disrupting mTORC2 offers a promising strategy for skin longevity. To assess age-related mTORC1 activity in fibroblasts and evaluate RLX-201, a novel mTOR inhibitor, and its effects on mTORC1 and mTORC2 activity in skin fibroblasts. Human dermal fibroblasts from young (23 years) and older (56 years) donors were analyzed for total and phosphorylated RPS6 by immunocytochemistry and automated western blotting. RLX-201's effects on mTORC1 (p70S6K) and mTORC2 (pAKT Ser473) were measured using HTRF assays. Older fibroblasts showed increased p-RPS6 levels, indicating higher basal mTORC1 activity. RLX-201 selectively inhibited mTORC1 without suppressing mTORC2, unlike high-dose rapamycin, which reduced both. RLX-201 treatment appears to alter the morphology of fibroblasts to a younger phenotype. mTORC1 hyperactivity is a key feature of aging fibroblasts and contributes to skin aging. RLX-201 enables selective mTORC1 inhibition while preserving mTORC2 activity, supporting its potential to counteract aging-related skin dysfunction and promote skin longevity. Treatment with RLX-201 can rejuvenate the fibroblasts increasing their functionality.