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.Electronic supplementary materialThe online version of this article (10.1007/s11357-019-00113-y) contains supplementary material, which is available to authorized users.

IMPORTANCE The risk for skin cancer has been well characterized in white organ transplant recipients (OTRs); however, most patients on the waiting list for organ transplant in the United States are nonwhite. Little is known about cutaneous disease and skin cancer risk in this OTR population. OBJECTIVE To compare the incidence of cutaneous disease between white and nonwhite OTRs. DESIGN, SETTING, AND PARTICIPANTS This retrospective review of medical records included 412 OTRs treated from November 1, 2011, through April 22, 2016, at an academic referral center. Prevalence and characteristics of cutaneous disease were compared in 154 white and 258 nonwhite (ie, Asian, Hispanic, and black) OTRs. Clinical factors of cutaneous disease and other common diagnoses assessed in OTRs included demographic characteristics, frequency and type of cancer, anatomical location, time course, sun exposure, risk awareness, and preventive behavior. MAIN OUTCOMES AND MEASURES Primary diagnosis of malignant or premalignant, infectious, and inflammatory disease. RESULTS The 412 patients undergoing analysis included 264 men (64.1%) and 148 women (35.9%), with a mean age of 60.1 years (range, 32.1-94.3 years). White OTRs more commonly had malignant disease at their first visit (82 [67.8%]), whereas nonwhite OTRs presented more commonly with infectious (63 [37.5%]) and inflammatory (82 [48.8%]) conditions. Skin cancer was diagnosed in 64 (41.6%) white OTRs and 15 (5.8%) nonwhite OTRs. Most lesions in white (294 of 370 [79.5%]) and Asian (5 of 6 [83.3%]) OTRs occurred in sun-exposed areas. Among black OTRs, 6 of 9 lesions (66.7%) occurred in sun-protected areas, specifically the genitals. Fewer nonwhite than white OTRs reported having regular dermatologic examinations (5 [11.4%] vs 8 [36.4%]) and knowing the signs of skin cancer (11 [25.0%] vs 10 [45.4%]). CONCLUSIONS AND RELEVANCE Early treatment of nonwhite OTRs should focus on inflammatory and infectious diseases. Sun protection should continue to be emphasized in white, Asian, and Hispanic OTRs. Black OTRs should be counseled to recognize the signs of genital human papillomavirus infection. Optimal posttransplant dermatologic care may be determined based on the race or ethnicity of the patients, but a baseline full-skin assessment should be performed in all patients. All nonwhite OTRs should be counseled more effectively on the signs of skin cancer, with focused discussion points contingent on skin type and race or ethnicity.

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IMPORTANCE Squamous cell carcinoma (SCC) is the most common skin cancer diagnosed in solid organ transplant recipients (OTRs) and confers significant mortality. The development of SCC in the genital region is elevated in nonwhite OTRs. Viral induction, specifically human papillomavirus (HPV), is hypothesized to play a role in the pathophysiology of these lesions. OBJECTIVE To assess the prevalence and types of genital lesions observed in OTRs. DESIGN, SETTING, AND PARTICIPANTS This retrospective review included 496 OTRs who underwent full skin examination from November 1, 2011, to April 28, 2017, at an academic referral center. The review was divided into 2 distinct periods before a change in clinical management that took effect on February 1, 2016 (era 1) and after that change (era 2). Patient awareness of genital lesions was assessed. All lesions clinically suggestive of malignant tumors were biopsied and underwent HPV polymerase chain reaction typing. MAIN OUTCOMES AND MEASURES Number and types of genital lesions, proportion of malignant tumors positive for HPV, and patients cognizant of genital lesions. RESULTS Of the total 496 OTRs, 376 OTRs were evaluated during era 1 (mean [SD] age, 60 years; age range, 32-94 years; 45 [65.2%] male; 164 [43.6%] white) and 120 OTRs were evaluated during era 2 of the study (mean age, 56 years; age range, 22-79 years; 76 [63.3%] male; 30 [25.0%] white). Overall, 111 of the 120 OTRs (92.5%) denied the presence of genital lesions during the history-taking portion of the medical examination. Genital lesions were found in 53 OTRs (44.2%), cutaneous malignant tumors (basal cell carcinoma and SCC in situ) in 6 (5.0%), genital SCC in situ in 3 (4.2%), and condyloma in 29 (24.2%). Eight of the 12 SCC in situ lesions (66.7%) were positive for high-risk HPV. Seven tested positive for HPV-16 and HPV-18, and 1 tested positive for high-risk HPV DNA but could not be further specified. CONCLUSIONS AND RELEVANCE Genital lesions in OTRs are common, but awareness is low. All OTRs should undergo thorough inspection of genital skin as a part of routine posttransplant skin examinations. Patients with darker skin types are disproportionately affected by cutaneous genital malignant tumors and should undergo a targeted program of early detection, prevention, and awareness focused on the risk of genital skin cancer after transplant. High-risk HPV subtypes are associated with genital SCC in OTRs. Additional studies are warranted to identify significant risk factors for HPV infection and to assess the utility of pretransplant HPV vaccination in the prevention of cutaneous genital malignant tumors.