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RLX-201, a Novel mTORC1 Inhibitor With Potential to Promote Skin Longevity and Cellular Health
Manpreet Randhawa1, Krzysztof Bojanowski2, Teresa Ferraro3
1Rapalogix Health Inc., New York, New York.
Targeting mechanistic target of rapamycin complex 1 (mTORC1) with RLX-201 selectively inhibits aging-related fibroblast hyperactivity, preserving mTORC2 and promoting skin longevity.
Area of Science:
- Cellular senescence
- Aging research
- Dermatology
Background:
- Mechanistic target of rapamycin complex 1 (mTORC1) hyperactivity drives aging phenotypes, including extracellular matrix degradation.
- Targeting mTORC1 selectively offers a strategy for promoting skin longevity.
Purpose of the Study:
- Assess age-related mTORC1 activity in fibroblasts.
- Evaluate the novel mTOR inhibitor RLX-201 for its effects on mTORC1 and mTORC2 in skin fibroblasts.
Main Methods:
- Human dermal fibroblasts from young and older donors analyzed for phosphorylated RPS6 (p-RPS6).
- RLX-201's impact on mTORC1 (p70S6K) and mTORC2 (pAKT Ser473) assessed via HTRF assays.
Main Results:
- Older fibroblasts exhibited elevated basal mTORC1 activity (higher p-RPS6).
- RLX-201 selectively inhibited mTORC1 without affecting mTORC2, unlike rapamycin.
- RLX-201 treatment shifted fibroblast morphology towards a younger phenotype.
Conclusions:
- mTORC1 hyperactivity is a hallmark of aging fibroblasts, contributing to skin aging.
- RLX-201 selectively inhibits mTORC1, preserving mTORC2, and may counteract skin aging.
- RLX-201 rejuvenates fibroblast function, supporting its potential for skin longevity.
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