Genetic basis for skin youthfulness.

Aging skin is a consequence of both intrinsic factors, including genetics, and extrinsic factors, including environmental exposures such as ultraviolet (UV) radiation and smoking. This contribution focuses on intrinsic factors that promote aging skin. Specifically, in this contribution we review the literature describing how single nucleotide polymorphisms, epigenetic changes, variable gene expression, microRNA, and mitochondrial depletion relate to skin aging. Investigations studying intrinsic factors associated with skin aging are important as they promote a better understanding of the underlying pathophysiology of aging skin. This contribution also describes potential avenues for future genetic research in skin aging. Molecular mechanisms that may be therapeutically intervened upon are of particular interest given the cultural value placed on youthful appearing skin. Future research efforts will hopefully reveal a means upon which to intercede on the skin aging process.

Age-induced and photoinduced changes in gene expression profiles in facial skin of Caucasian females across 6 decades of age.

BACKGROUND: Intrinsic and extrinsic factors, including ultraviolet irradiation, lead to visible signs of skin aging. OBJECTIVE: We evaluated molecular changes occurring in photoexposed and photoprotected skin of white women 20 to 74 years of age, some of whom appeared substantially younger than their chronologic age. METHODS: Histologic and transcriptomics profiling were conducted on skin biopsy samples of photoexposed (face and dorsal forearm) or photoprotected (buttocks) body sites from 158 women. 23andMe genotyping determined genetic ancestry. RESULTS: Gene expression and ontologic analysis revealed progressive changes from the 20s to the 70s in pathways related to oxidative stress, energy metabolism, senescence, and epidermal barrier; these changes were accelerated in the 60s and 70s. The gene expression patterns from the subset of women who were younger-appearing were similar to those in women who were actually younger. LIMITATIONS: Broader application of these findings (eg, across races and Fitzpatrick skin types) will require further studies. CONCLUSIONS: This study demonstrates a wide range of molecular processes in skin affected by aging, providing relevant targets for improving the condition of aging skin at different life stages and defining a molecular pattern of epidermal gene expression in women who appear younger than their chronologic age.

A Preliminary, Open Label, Single-arm Study of Calcipotriene/Betamethasone Topical Suspension as a Supplement to Non-biologic Systemic Therapy for Psoriasis.

BACKGROUND: Calcipotriene/betamethasone topical suspension is a topical therapy that is often used as monotherapy as a first-line treatment for plaque psoriasis. The objective of this preliminary, open label, single arm study was to determine the efficacy of adding a topical suspension to a traditional systemic therapy for psoriasis, either methotrexate or acitretin. METHODS: In this exploratory study, eight patients with chronic plaque psoriasis who were on stable methotrexate or acitretin treatment without clearance were treated with once-daily calcipotriene/betamethasone topical suspension. Subjects completed five study visits over 12 weeks. Primary outcome measure was improvement of two or more points in Investigator Global Assessment. Secondary endpoints included change in Body Surface Area, Dermatology Life Quality Index, and Patient's Global Assessment from baseline to Week 12. RESULTS: Overall, the median decrease in Investigator Global Assessment over 12 weeks was 1.5 points, with 50 percent of subjects experiencing a drop of two or more points in Investigator Global Assessment. All eight subjects had a reduction in Body Surface Area and Patient's Global Assessment. There was a mean decrease in Dermatology Life Quality Index score of 78.9 percent, showing improved patient quality of life. In addition, all patients tolerated the treatment well and 6 of 8 patients had improved satisfaction level with their treatment by the end of the study. CONCLUSION: The topical suspension was effective and well-tolerated in conjunction with stable methotrexate or acitretin treatment in all eight patients in this study. These results support the feasibility of a larger scale study to further investigate the efficacy of these treatment combinations. The trial is registered at ClinicalTrials.gov, number NCT01761019.