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Skin Aging and Gene Expression

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 August 2018) | Viewed by 59659

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Department of Physiology & Developmental Biology and the Neuroscience Center, Brigham Young University, Provo, UT, USA
Interests: dermatology; testosterone; estrogens; steroids; endocrine disruption; reproductive endocrinology; molecular endocrinology; neuroendocrinology; stress physiology; reproductive biology
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Dear Colleagues,

As a result of the human genome project (from 1990 to 2003), a multitude of studies, mainly based on microarray technology, have been conducted to map gene expression in various human cell and tissue types, including skin. Many basic research laboratories and cosmetic companies utilize in vitro gene array studies to display significant stimulation or inhibition of various human skin biomarkers to generate hypotheses of how natural products or different ingredients enhance dermal health. This is not surprising, since human skin, due to its important barrier/defense function, was among the first organs to be studied by gene arrays. It is well established that a gradual decline in overall skin physiology occurs with aging including structural changes in the epidermis and dermis along with functional changes in fibroblasts and other cellular components that are linked to the expression of skin-related genes and proteins. These skin-related genes have been grouped into many different categories, such as extra cellular matrix components, antioxidants, growth factors, tissue repair, along with inflammatory and aging biomarkers that change with intrinsic aging and photo-aging. The goal is to understand how human skin ages and what agents and mechanisms are available to slow down this process so that individuals can recover from dermal trauma and delay intrinsic and photo-aging to improve their self-perception and feel better about themselves. This Special Issue covers these aspects of “Skin Aging and Gene Expression”, from a basic science perspective to commercial dermal applications.

Prof. Dr. Edwin Lephart
Guest Editor

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Keywords

  • Skin
  • Aging
  • Gene Expression
  • Dermal Components
  • Oxidative Stress
  • Anti-Aging
  • Anti-Photoaging
  • Skin Biomarkers

Published Papers (5 papers)

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Research

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14 pages, 1331 KiB  
Article
Assessment of Human Skin Gene Expression by Different Blends of Plant Extracts with Implications to Periorbital Skin Aging
by Jin Namkoong, Dale Kern and Helen E. Knaggs
Int. J. Mol. Sci. 2018, 19(11), 3349; https://doi.org/10.3390/ijms19113349 - 26 Oct 2018
Cited by 9 | Viewed by 4987
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Skin Aging and Gene Expression)
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15 pages, 9392 KiB  
Article
Air Pollution, Autophagy, and Skin Aging: Impact of Particulate Matter (PM10) on Human Dermal Fibroblasts
by Seo-Yeon Park, Eun Jung Byun, Jeong Deuk Lee, Sungjoo Kim and Hei Sung Kim
Int. J. Mol. Sci. 2018, 19(9), 2727; https://doi.org/10.3390/ijms19092727 - 12 Sep 2018
Cited by 70 | Viewed by 8983
Abstract
A World Health Organization (WHO) report from 2016 states that over 3 million people die annually from air pollution, which places air pollution as the world’s largest single environmental health risk factor. Particulate matter (PM) is one of the main components of air [...] Read more.
A World Health Organization (WHO) report from 2016 states that over 3 million people die annually from air pollution, which places air pollution as the world’s largest single environmental health risk factor. Particulate matter (PM) is one of the main components of air pollution, and there is increasing evidence that PM exposure exerts negative effects on the human skin. To see the impact of air pollution on skin aging, we analyzed the effect of PM exposure on human dermal fibroblasts (HDFs) with Western blot, enzyme-linked immunosorbent assay (ELISA), and gene analysis. Cultured HDFs were exposed to PM10 at a concentration of 30 µg/cm2 for 24 h, and their gene/protein expression of inflammatory cytokines, fibroblast chemical mediators, and autophagy were assessed. A total of 1977 genes were found to be differentially expressed following PM exposure. We observed a significantly increased expression of pro-inflammatory genes interleukin (IL)-1β, IL-6, IL-8 and IL-33 in dermal fibroblasts exposed to PM10. Protein expression of IL-6 and IL-8 also significantly increased, which complemented our gene analysis results. In addition, there was a significant increase in cytochrome P450 (CYP1A1, CYP1B1), matrix metalloproteinase (MMP-1, MMP-3) mRNA expression, and significant decrease in transforming growth factor (TGF)-β, collagen type I alpha chain (COL1A1, COL1A2), and elastin (ELN) mRNA expression in PM-exposed dermal fibroblasts. Protein expression of MMP-1 was significantly increased and that of TGF-β and procollagen profoundly decreased, similar to the gene analysis results. Autophagy, an integrated cellular stress response, was also increased while transmission electron microscopy (TEM) analysis provided evidence of PM internalization in the autolysosomes. Taken together, our results demonstrate that PM10 contributes to skin inflammation and skin aging via impaired collagen synthesis. Increased autophagy in our study suggests a reparative role of autophagy in HDFs stressed with PM, but its biological significance requires further research. Full article
(This article belongs to the Special Issue Skin Aging and Gene Expression)
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13 pages, 3970 KiB  
Article
Autophagy in Human Skin Fibroblasts: Impact of Age
by Hei Sung Kim, Seo-Yeon Park, Seok Hoon Moon, Jeong Deuk Lee and Sungjoo Kim
Int. J. Mol. Sci. 2018, 19(8), 2254; https://doi.org/10.3390/ijms19082254 - 01 Aug 2018
Cited by 35 | Viewed by 6591
Abstract
Autophagy is an intracellular stress response that is enhanced under starvation conditions, and also when the cellular components are damaged. Aging accompanies an increase in intracellular stress and has significant impact on the skin. Since dermal fibroblasts are a powerful indicator of skin [...] Read more.
Autophagy is an intracellular stress response that is enhanced under starvation conditions, and also when the cellular components are damaged. Aging accompanies an increase in intracellular stress and has significant impact on the skin. Since dermal fibroblasts are a powerful indicator of skin aging, we compared the autophagic activity of human skin fibroblasts between the young and old. According to TEM analyses, the number of autophagosomes per 1 μm2 cytoplasmic area was similar between young and aged fibroblasts. The amount of LC3 (microtubule-associated protein 1 light chain 3)-II, a form associated with autophagic vacuolar membranes, was also similar between the groups from Western blot analysis. Although residual bodies were more common in aged dermal fibroblasts, LC3 turnover and p62 assay showed little difference in the rate of lysosomal proteolysis between the young and old. RNA-seq analysis revealed that the major autophagy-modulating genes (BECN1, MAP1LC3B, ATG5, ATG7, ULK1, PIK3C3, mTOR) were not differentially expressed with age. Our results suggest that the basal autophagic flux in aged dermal fibroblasts is largely comparable to that of young fibroblasts. However, with a higher speed and amount of waste production in aged cells, we postulate that such autophagic flux may not be sufficient in keeping the old cells “clean”, resulting in skin aging. Aging is a complex process and, as such, the relationship between autophagy and aging is not straightforward. That is to say, autophagy does not simply decline with age. Regardless of the controversies on autophagic activity with age, autophagy plays a crucial role in counteracting aging, and strategies aimed at its modulation should hold promise for the prevention of skin aging. Full article
(This article belongs to the Special Issue Skin Aging and Gene Expression)
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18 pages, 22094 KiB  
Article
Exosomes Derived from Human Induced Pluripotent Stem Cells Ameliorate the Aging of Skin Fibroblasts
by Myeongsik Oh, Jinhee Lee, Yu Jin Kim, Won Jong Rhee and Ju Hyun Park
Int. J. Mol. Sci. 2018, 19(6), 1715; https://doi.org/10.3390/ijms19061715 - 09 Jun 2018
Cited by 135 | Viewed by 13149
Abstract
Stem cells and their paracrine factors have emerged as a resource for regenerative medicine. Many studies have shown the beneficial effects of paracrine factors secreted from adult stem cells, such as exosomes, on skin aging. However, to date, few reports have demonstrated the [...] Read more.
Stem cells and their paracrine factors have emerged as a resource for regenerative medicine. Many studies have shown the beneficial effects of paracrine factors secreted from adult stem cells, such as exosomes, on skin aging. However, to date, few reports have demonstrated the use of exosomes derived from human pluripotent stem cells for the treatment of skin aging. In this study, we collected exosomes from the conditioned medium of human induced pluripotent stem cells (iPSCs) and investigated the effect on aged human dermal fibroblasts (HDFs). Cell proliferation and viability were determined by an MTT assay and cell migration capacity was shown by a scratch wound assay and a transwell migration assay. To induce photoaging and natural senescence, HDFs were irradiated by UVB (315 nm) and subcultured for over 30 passages, respectively. The expression level of certain mRNAs was evaluated by quantitative real-time PCR (qPCR). Senescence-associated-β-galactosidase (SA-β-Gal) activity was assessed as a marker of natural senescence. As a result, we found that exosomes derived from human iPSCs (iPSCs-Exo) stimulated the proliferation and migration of HDFs under normal conditions. Pretreatment with iPSCs-Exo inhibited the damages of HDFs and overexpression of matrix-degrading enzymes (MMP-1/3) caused by UVB irradiation. The iPSCs-Exo also increased the expression level of collagen type I in the photo-aged HDFs. In addition, we demonstrated that iPSCs-Exo significantly reduced the expression level of SA-β-Gal and MMP-1/3 and restored the collagen type I expression in senescent HDFs. Taken together, it is anticipated that these results suggest a therapeutic potential of iPSCs-Exo for the treatment of skin aging. Full article
(This article belongs to the Special Issue Skin Aging and Gene Expression)
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35 pages, 2761 KiB  
Review
Enhancing Skin Health: By Oral Administration of Natural Compounds and Minerals with Implications to the Dermal Microbiome
by David L. Vollmer, Virginia A. West and Edwin D. Lephart
Int. J. Mol. Sci. 2018, 19(10), 3059; https://doi.org/10.3390/ijms19103059 - 07 Oct 2018
Cited by 74 | Viewed by 25076
Abstract
The history of cosmetics goes back to early Egyptian times for hygiene and health benefits while the history of topical applications that provide a medicinal treatment to combat dermal aging is relatively new. For example, the term cosmeceutical was first coined by Albert [...] Read more.
The history of cosmetics goes back to early Egyptian times for hygiene and health benefits while the history of topical applications that provide a medicinal treatment to combat dermal aging is relatively new. For example, the term cosmeceutical was first coined by Albert Kligman in 1984 to describe topical products that afford both cosmetic and therapeutic benefits. However, beauty comes from the inside. Therefore, for some time scientists have considered how nutrition reflects healthy skin and the aging process. The more recent link between nutrition and skin aging began in earnest around the year 2000 with the demonstrated increase in peer-reviewed scientific journal reports on this topic that included biochemical and molecular mechanisms of action. Thus, the application of: (a) topical administration from outside into the skin and (b) inside by oral consumption of nutritionals to the outer skin layers is now common place and many journal reports exhibit significant improvement for both on a variety of dermal parameters. Therefore, this review covers, where applicable, the history, chemical structure, and sources such as biological and biomedical properties in the skin along with animal and clinical data on the oral applications of: (a) collagen, (b) ceramide, (c) β-carotene, (d) astaxanthin, (e) coenzyme Q10, (f) colostrum, (g) zinc, and (h) selenium in their mode of action or function in improving dermal health by various quantified endpoints. Lastly, the importance of the human skin microbiome is briefly discussed in reference to the genomics, measurement, and factors influencing its expression and how it may alter the immune system, various dermal disorders, and potentially be involved in chemoprevention. Full article
(This article belongs to the Special Issue Skin Aging and Gene Expression)
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