Format

Send to

Choose Destination
Geroscience. 2019 Dec;41(6):861-869. doi: 10.1007/s11357-019-00113-y. Epub 2019 Nov 25.

Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial.

Author information

1
Department of Dermatology, Drexel University College of Medicine, Philadelphia, PA, USA.
2
Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USA.
3
Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, 245 N 15th Street, Philadelphia, PA, 19102, USA.
4
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
5
Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, 245 N 15th Street, Philadelphia, PA, 19102, USA. cs389@drexel.edu.
6
Department of Biochemistry, Drexel University College of Medicine, Philadelphia, PA, USA. cs389@drexel.edu.

Abstract

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.

KEYWORDS:

aging; keratoses; mTOR; photoaging; rapamycin; senescence

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center