Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial
| Autor: | Christina Lee Chung, Ibiyonu Lawrence, Melissa Hoffman, Manali Potnis, Christian Sell, Kumar S. Nadhan, Catlin Sershon, Dareen Elgindi, Annie Jin, Antonello Lorenzini, Rhonda Binnebose |
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| Přispěvatelé: | Chung C.L., Lawrence I., Hoffman M., Elgindi D., Nadhan K., Potnis M., Jin A., Sershon C., Binnebose R., Lorenzini A., Sell C. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Senescence medicine.medical_specialty senescence photoaging Photoaging Human skin Disease law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law Internal medicine Medicine Mechanistic target of rapamycin biology business.industry rapamycin keratose aging Cancer medicine.disease 030104 developmental biology keratoses biology.protein mTOR Dermal atrophy Original Article Geriatrics and Gerontology business 030217 neurology & neurosurgery |
| Zdroj: | GeroScience |
| ISSN: | 2509-2723 2509-2715 |
| Popis: | Aging is a major risk factor for the majority of human diseases, and the development of interventions to reduce the intrinsic rate of aging is expected to reduce the risk for age-related diseases including cardiovascular disease, cancer, and dementia. In the skin, aging manifests itself in photodamage and dermal atrophy, with underlying tissue reduction and impaired barrier function. To determine whether rapamycin, an FDA-approved drug targeting the mechanistic target of rapamycin (mTOR) complex, can reduce senescence and markers of aging in human skin, an exploratory, placebo-controlled, interventional trial was conducted in a clinical dermatology setting. Participants were greater than 40 years of age with evidence of age-related photoaging and dermal volume loss and no major morbidities. Thirty-six participants were enrolled in the study, and nineteen discontinued or were lost to follow-up. A significant (P = 0.008) reduction in p16INK4A protein levels and an increase in collagen VII protein levels (P = 0.0077) were observed among participants at the end of the study. Clinical improvement in skin appearance was noted in multiple participants, and immunohistochemical analysis revealed improvement in histological appearance of skin tissue. Topical rapamycin reduced the expression of the p16INK4A protein consistent with a reduction in cellular senescence. This change was accompanied by relative improvement in clinical appearance of the skin and histological markers of aging and by an increase in collagen VII, which is critical to the integrity of the basement membrane. These results indicate that rapamycin treatment is a potential anti-aging therapy with efficacy in humans.Trial registration ClinicalTrials.gov Identifier: NCT03103893. |
| Databáze: | OpenAIRE |
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