PMID- 31761958
OWN - NLM
STAT- MEDLINE
DCOM- 20200709
LR  - 20200709
IS  - 2509-2723 (Electronic)
IS  - 2509-2715 (Print)
IS  - 2509-2723 (Linking)
VI  - 41
IP  - 6
DP  - 2019 Dec
TI  - Topical rapamycin reduces markers of senescence and aging in human skin: an 
      exploratory, prospective, randomized trial.
PG  - 861-869
LID - 10.1007/s11357-019-00113-y [doi]
AB  - 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 p16(INK4A) 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 p16(INK4A) 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.
FAU - Chung, Christina Lee
AU  - Chung CL
AD  - Department of Dermatology, Drexel University College of Medicine, Philadelphia, 
      PA, USA.
FAU - Lawrence, Ibiyonu
AU  - Lawrence I
AD  - Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, 
      USA.
FAU - Hoffman, Melissa
AU  - Hoffman M
AD  - Department of Dermatology, Drexel University College of Medicine, Philadelphia, 
      PA, USA.
FAU - Elgindi, Dareen
AU  - Elgindi D
AD  - Department of Dermatology, Drexel University College of Medicine, Philadelphia, 
      PA, USA.
FAU - Nadhan, Kumar
AU  - Nadhan K
AD  - Department of Dermatology, Drexel University College of Medicine, Philadelphia, 
      PA, USA.
FAU - Potnis, Manali
AU  - Potnis M
AD  - Department of Pathology and Laboratory Medicine, Drexel University College of 
      Medicine, 245 N 15th Street, Philadelphia, PA, 19102, USA.
FAU - Jin, Annie
AU  - Jin A
AD  - Department of Dermatology, Drexel University College of Medicine, Philadelphia, 
      PA, USA.
FAU - Sershon, Catlin
AU  - Sershon C
AD  - Department of Dermatology, Drexel University College of Medicine, Philadelphia, 
      PA, USA.
FAU - Binnebose, Rhonda
AU  - Binnebose R
AD  - Department of Pathology and Laboratory Medicine, Drexel University College of 
      Medicine, 245 N 15th Street, Philadelphia, PA, 19102, USA.
FAU - Lorenzini, Antonello
AU  - Lorenzini A
AD  - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, 
      Italy.
FAU - Sell, Christian
AU  - Sell C
AUID- ORCID: 0000-0002-4332-1141
AD  - Department of Pathology and Laboratory Medicine, Drexel University College of 
      Medicine, 245 N 15th Street, Philadelphia, PA, 19102, USA. cs389@drexel.edu.
AD  - Department of Biochemistry, Drexel University College of Medicine, Philadelphia, 
      PA, USA. cs389@drexel.edu.
LA  - eng
SI  - ClinicalTrials.gov/NCT03103893
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20191125
PL  - Switzerland
TA  - Geroscience
JT  - GeroScience
JID - 101686284
RN  - 0 (Collagen Type VII)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Immunosuppressive Agents)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - Geroscience. 2020 Apr;42(2):813-815. PMID: 32227278
MH  - Administration, Topical
MH  - Adult
MH  - Biopsy
MH  - Cellular Senescence/drug effects
MH  - Collagen Type VII/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p16/metabolism
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunosuppressive Agents/administration & dosage
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Sirolimus/*administration & dosage
MH  - Skin/*drug effects/metabolism/pathology
MH  - Skin Aging/*drug effects
MH  - Skin Diseases/*drug therapy/metabolism/pathology
PMC - PMC6925069
OTO - NOTNLM
OT  - aging
OT  - keratoses
OT  - mTOR
OT  - photoaging
OT  - rapamycin
OT  - senescence
EDAT- 2019/11/26 06:00
MHDA- 2020/07/10 06:00
PMCR- 2019/11/25
CRDT- 2019/11/26 06:00
PHST- 2019/10/03 00:00 [received]
PHST- 2019/10/09 00:00 [accepted]
PHST- 2019/11/26 06:00 [pubmed]
PHST- 2020/07/10 06:00 [medline]
PHST- 2019/11/26 06:00 [entrez]
PHST- 2019/11/25 00:00 [pmc-release]
AID - 10.1007/s11357-019-00113-y [pii]
AID - 113 [pii]
AID - 10.1007/s11357-019-00113-y [doi]
PST - ppublish
SO  - Geroscience. 2019 Dec;41(6):861-869. doi: 10.1007/s11357-019-00113-y. Epub 2019 
      Nov 25.