Dale Kern

A Two-Year, Double-Blind, Randomized Placebo-Controlled Trial of Oral Green Tea Polyphenols on the Long-Term Clinical and Histologic Appearance of Photoaging Skin

BACKGROUND Green tea polyphenols (GTPs) have significant antioxidant and antiinflammatory activities, and prior short‐term studies suggest that these compounds may improve photoaging skin. OBJECTIVES To evaluate the long‐term effects of oral GTPs on the clinical and histologic characteristics of photoaging skin. MATERIALS AND METHODS Double‐blind, placebo‐controlled trial of 56 women aged 25 to 75 randomized to 250 mg GTPs or placebo twice daily for 2 years. A blinded dermatologist scored the appearance of photodamaged facial skin at 0, 6, 12, and 24 months. A blinded dermatopathologist scored the histologic characteristics of sun‐exposed arm skin at 0 and 24 months. RESULTS Clinical assessment of facial skin revealed that the GTP group had significant improvement in overall solar damage at 6 months (p=.02) and significant improvement in erythema and telangiectasias at 12 months (p=.02). The placebo group did not have significant improvements in these parameters at 6 months or 12 months. There were no statistically significant differences in other photoaging parameters at 6, 12, or 24 months in the GTP or placebo groups. Histopathologic analysis of sunexposed arm skin showed no statistically significant difference in photoaging parameters in the GTP group or the placebo group at 24 months. CONCLUSIONS Long‐term supplementation with oral GTPs was not superior to placebo in improving clinical or histologic photoaging parameters after 24 months of use. Funding and materials for this study were provided by Nu Skin, Provo, Utah. Dale Kern is an employee of Nu Skin International.

Controlling Reactive Oxygen Species in Skin at Their Source to Reduce Skin Aging

Activity of an age-related, superoxide-forming, cell-surface oxidase (arNOX) comparing dermis, epidermis, serum, and saliva from female and male subjects ages 28-72 years measured spectrophotometrically using reduction of ferricytochrome c correlated with oxidative skin damage as estimated from autofluoresence of skin using an Advanced Glycation End products Reader (AGE-Reader; DiagnOptics B.V., Netherlands). By reducing arNOX activity in skin with arNOX-inhibitory ingredients (NuSkins ageLOC technology), skin appearance was improved through decreased protein cross-linking and an accelerated increase in collagen.

Age-related NADH oxidase (arNOX)-catalyzed oxidative damage to skin proteins.

Abstract Age-related NADH oxidase (arNOX), a cell surface-located hydroquinone oxidase capable of superoxide generation, appears at age 30 and increases with age thereafter. The ectodomain of arNOX is shed from the cell surface into body fluids including sera and saliva where its activity was measured spectrophotometrically using a reduction of ferricytochrome c as a measure of superoxide generation. The autofluorescence of advanced glycation end products correlates with epidermal arNOX activity as well. To demonstrate protein cross-linking, a fluorescence-labeled analog of tyrosine, tyramine, that would react with proteins carrying arNOX-generated tyrosyl radicals was used. The assay demonstrated the potential for arNOX-induced oxidative damage (dityrosine formation) to human collagen and elastin and to other surface proteins of intact human embryo fibroblasts and frozen sections from epidermal punch biopsies. The findings support a role for arNOX as a major source of oxidative damage leading to cross-linking of skin proteins.

Assessment of Human Skin Gene Expression by Different Blends of Plant Extracts with Implications to Periorbital Skin Aging

Since the skin is the major protective barrier of the body, it is affected by intrinsic and extrinsic factors. Environmental influences such as ultraviolet (UV) irradiation, pollution or dry/cold air are involved in the generation of radical oxygen species (ROS) and impact skin aging and dermal health. Assessment of human skin gene expression and other biomarkers including epigenetic factors are used to evaluate the biological/molecular activities of key compounds in cosmetic formulas. The objective of this study was to quantify human gene expression when epidermal full-thickness skin equivalents were exposed to: (a) a mixture of betaine, pentylene glycol, Saccharomyces cerevisiae and Rhodiola rosea root extract (BlendE) for antioxidant, skin barrier function and oxidative stress (with hydrogen peroxide challenge); and (b) a mixture of Narcissus tazetta bulb extract and Schisandra chinensis fruit extract (BlendIP) for various biomarkers and microRNA analysis. For BlendE, several antioxidants, protective oxidative stress biomarkers and many skin barrier function parameters were significantly increased. When BlendE was evaluated, the negative impact of the hydrogen peroxide was significantly reduced for the matrix metalloproteinases (MMP 3 and MMP 12), the skin aging and oxidative stress biomarkers, namely FBN2, ANXA1 and HGF. When BlendIP was tested for cell proliferation and dermal structural components to enhance the integrity of the skin around the eyes: 8 growth factors, 7 signaling, 7 structural/barrier function and 7 oxidative stress biomarkers were significantly increased. Finally, when BlendIP was tested via real-time RT-PCR for microRNA expression: miR-146a, miR-22, miR155, miR16 and miR21 were all significantly increased over control levels. Therefore, human skin gene expression studies are important tools to assess active ingredient compounds such as plant extract blends to advance dermal hypotheses toward validating cosmetic formulations with botanical molecules.

Protective effects of a novel nutritional and phytonutrient blend on ultraviolet radiation‐induced skin damage and inflammatory response through aging defense mechanisms

The human body relies on several aging defense mechanisms (ADMs) to limit damage induced from pro‐aging stressors (aging aggressors). However, such protective mechanisms can be compromised, leading to accelerated aging. The skin provides a model to probe the effects of an oral nutritional intervention on ADMs in response to ultraviolet radiation (UVR)‐induced damage.

Novel Gene Expression Profile of Women with Intrinsic Skin Youthfulness by Whole Transcriptome Sequencing.

While much is known about genes that promote aging, little is known about genes that protect against or prevent aging, particularly in human skin. The main objective of this study was to perform an unbiased, whole transcriptome search for genes that associate with intrinsic skin youthfulness. To accomplish this, healthy women (n = 122) of European descent, ages 18–89 years with Fitzpatrick skin type I/II were examined for facial skin aging parameters and clinical covariates, including smoking and ultraviolet exposure. Skin youthfulness was defined as the top 10% of individuals whose assessed skin aging features were most discrepant with their chronological ages. Skin biopsies from sun-protected inner arm were subjected to 3’-end sequencing for expression quantification, with results verified by quantitative reverse transcriptase-polymerase chain reaction. Unbiased clustering revealed gene expression signatures characteristic of older women with skin youthfulness (n = 12) compared to older women without skin youthfulness (n = 33), after accounting for gene expression changes associated with chronological age alone. Gene set analysis was performed using Genomica open-access software. This study identified a novel set of candidate skin youthfulness genes demonstrating differences between SY and non-SY group, including pleckstrin homology like domain family A member 1 (PHLDA1) (p = 2.4x10-5), a follicle stem cell marker, and hyaluronan synthase 2-anti-sense 1 (HAS2-AS1) (p = 0.00105), a non-coding RNA that is part of the hyaluronan synthesis pathway. We show that immunologic gene sets are the most significantly altered in skin youthfulness (with the most significant gene set p = 2.4x10-5), suggesting the immune system plays an important role in skin youthfulness, a finding that has not previously been recognized. These results are a valuable resource from which multiple future studies may be undertaken to better understand the mechanisms that promote skin youthfulness in humans.

An Exploratory Study to Determine the Association Between Assessed Facial Skin Aging and Plasma Isoprostane Levels in Middle‐Aged Japanese Women

Background One of the central mechanisms of aging is hypothesized to be oxidative stress. Quantification of oxidative stress in human organ systems has been difficult. One of the best methods is using plasma isoprostane levels, which have been shown to reflect oxidative stress in multiple nondermatologic organ systems. Objective To determine whether severity of aging of human skin is associated with plasma isoprostane levels, specifically prostaglandin F2a (PGF2a) and 8‐iso‐PGF2a while controlling for covariates such as body mass index, ultraviolet light exposure, diet, medication, supplement use, and stress levels. Methods and Materials Facial skin aging assessments performed by four blinded dermatologists were correlated with plasma isoprostane levels in 46 healthy, nonsmoking Japanese women aged 45 to 60. Results Individuals whose assessed skin age exceeded chronological age had mean plasma isoprostane levels of PGF2a and 8‐iso‐PGF2a that were higher than those whose skin age was assessed to be less than chronological age (p = .001 and .001, respectively). These results remained statistically significant when adjusted for confounding variables (8‐iso‐PGF2a, p = .02; PGF2a, p = .03). Conclusions Plasma isoprostanes as markers of accelerated aging of the skin merit further study.