Aging-Associated Changes in the Adult Human Skin Microbiome and the Host Factors that Affect Skin Microbiome Composition.

Understanding the changes in the skin microbiome and their relationship to host skin factors during aging remains largely unknown. To better understand this phenomenon, we collected samples for metagenomic and host skin factor analyses from the forearm, buttock, and facial skin from 158 Caucasian females aged 20‒24, 30‒34, 40‒44, 50‒54, 60‒64, and 70‒74 years. Metagenomics analysis was performed using 16S ribosomal RNA gene sequencing, whereas host sebocyte gland area, skin lipids, natural moisturizing factors, and antimicrobial peptides measurements were also performed. These analyses showed that skin bacterial diversity increased at all the skin sites with increasing age. Of the bacterial genera with an average relative abundance >1%, only Lactobacillus and Cutibacterium demonstrated a significant change (decrease) in abundance at all sampled skin sites with increasing age. Additional bacterial genera demonstrated significant age- and site-specific changes in abundance. Analysis of sebocyte area, natural moisturizing factors, lipids, and antimicrobial peptides showed an age-related decrease in sebocyte area and increases in natural moisturizing factors/antimicrobial peptides/skin lipids, all of which correlated with changes in specific bacterial genera. In conclusion, the human skin microbiome undergoes age-associated alterations that may reflect underlying age-related changes in cutaneous biology.

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.

Self-assembly of palmitoyl lipopeptides used in skin care products.

The self-assembly of three cosmetically active peptide amphiphiles C16-GHK, C16-KT, and C16-KTTKS (C16 denotes a hexadecyl, palmitoyl chain) used in commercial skin care products is examined. A range of spectroscopic, microscopic, and X-ray scattering methods is used to probe the secondary structure, aggregate morphology, and the nanostructure. Peptide amphiphile (PA) C16-KTTKS forms flat tapes and extended fibrillar structures with high ß-sheet content. In contrast, C16-KT and C16-GHK exhibit crystal-like aggregates with, in the case of the latter PA, lower ß-sheet content. All three PA samples show spacings from bilayer structures in small-angle X-ray scattering profiles, and all three have similar critical aggregation concentrations, this being governed by the lipid chain length. However, only C16-KTTKS is stained by Congo red, a diagnostic dye used to detect amyloid formation, and this PA also shows a highly aligned cross-ß X-ray diffraction pattern consistent with the high ß-sheet content in the self-assembled aggregates. These findings may provide important insights relevant to the role of self-assembled aggregates on the reported collagen-stimulating properties of these PAs.

A proposed eye irritation testing strategy to reduce and replace in vivo studies using Bottom-Up and Top-Down approaches.

In spite of over 20 years of effort, no single in vitro assay has been developed and validated as a full regulatory replacement for the Draize Eye Irritation test. However, companies have been using in vitro methods to screen new formulations and in some cases as their primary assessment of eye irritation potential for many years. The present report shows the outcome of an Expert Meeting convened by the European Centre for the Validation of Alternative Methods in February 2005 to identify test strategies for eye irritation. In this workshop test developers/users were requested to nominate methods to be considered as a basis for the identification of such testing strategies. Assays were evaluated and categorized based on their proposed applicability domains (e.g., categories of irritation severity, modes of action, chemical class, physicochemical compatibility). The analyses were based on the data developed from current practice and published studies, the ability to predict depth of injury (within the applicable range of severity), modes of action that could be addressed and compatibility with different physiochemical forms. The difficulty in predicting the middle category of irritancy (e.g. R36, GHS Categories 2A and 2B) was recognized. The testing scheme proposes using a Bottom-Up (begin with using test methods that can accurately identify non-irritants) or Top-Down (begin with using test methods that can accurately identify severe irritants) progression of in vitro tests (based on expected irritancy). Irrespective of the starting point, the approach would identify non-irritants and severe irritants, leaving all others to the (mild/moderate) irritant GHS 2/R36 categories.

Understanding metabolic pathways for skin anti-aging.

Global gene expression profiling provides a useful means to identify key aspects of the skin aging process, and provides information to help develop new skin technologies. Important aspects of skin aging that can be addressed include skin hydration, barrier, matrix, pigmentation and antioxidant capacity. Human skin equivalent cultures allow topical application of test compounds, combinations and products to their stratum corneum surface and measurement of predictive biomarkers. Using this in vitro biomarker approach, it is possible to detect skin barrier enhancement in response to the compounds niacinamide and hexamidine, matrix effects to the peptides Pal-KT and Pal-KTTKS, and hydration and matrix responses to niacinamide and N-acetylglucosamine.

Proposed new classification scheme for chemical injury to the human eye.

PURPOSE: Various ocular alkali burn classification schemes have been published and used to grade human chemical eye injuries for the purpose of identifying treatments and forecasting outcomes. The ILSI chemical eye injury classification scheme was developed for the additional purpose of collecting detailed human eye injury data to provide information on the mechanisms associated with chemical eye injuries. This information will have clinical application, as well as use in the development and validation of new methods to assess ocular toxicity. METHODS: A panel of ophthalmic researchers proposed the new classification scheme based upon current knowledge of the mechanisms of eye injury, and their collective clinical and research experience. Additional ophthalmologists and researchers were surveyed to critique the scheme. The draft scheme was revised, and the proposed scheme represents the best consensus from at least 23 physicians and scientists. RESULTS: The new scheme classifies chemical eye injury into five categories based on clinical signs, symptoms, and expected outcomes. Diagnostic classification is based primarily on two clinical endpoints: (1) the extent (area) of injury at the limbus, and (2) the degree of injury (area and depth) to the cornea. CONCLUSIONS: The new classification scheme provides a uniform system for scoring eye injury across chemical classes, and provides enough detail for the clinician to collect data that will be relevant to identifying the mechanisms of ocular injury.