Aging-Like Skin Changes Induced by Ultraviolet Irradiation in an Animal Model of Metabolic Syndrome

2011 ◽  
Vol 14 (2) ◽  
pp. 180-187 ◽  
Author(s):  
Tomoko Akase ◽  
Takashi Nagase ◽  
Lijuan Huang ◽  
Ai Ibuki ◽  
Takeo Minematsu ◽  
...  

Both physiological skin aging and pathologic photo-aging caused by ultraviolet (UV) irradiation are mediated by latent inflammation and oxidative stress. Although numerous animal skin-aging models have used UV irradiation, most require massive doses or long-term irradiation. To establish a more refined skin-aging model, we focused on an animal model of metabolic syndrome (MS) because MS involves damage to various organs via oxidative stress or inflammation, similar to the changes associated with aging. We hypothesized that MS skin might exhibit more aging-like changes after milder, shorter-term UV irradiation than would normal animal skin under similar conditions, thus providing a useful model for skin aging. The authors therefore examined the skin from Tsumura Suzuki obese diabetic (TSOD) mice (MS model) and control Tsumura Suzuki non-obese (TSNO) mice before and after UV irradiation. Skin from TSOD mice had a thinner epidermis and dermis, a thicker fatty layer, reduced density and convolution of the fragmented collagen fibers, and upregulated expression of tumor necrosis factor (TNF)-α, a dual marker for inflammation and aging, compared to the skin from TSNO mice. UV irradiation affected TSOD skin more severely than TSNO skin, resulting in various changes resembling those in aged human skin, including damage to the dermis and subcutaneous fatty tissue, infiltration of inflammatory cells, and further upregulation of TNF-α expression. These results suggest that UV-irradiated TSOD mice may provide a new model of skin aging and imply that skin from humans with MS is more susceptible to UV- or aging-related damage than normal human skin.

2018 ◽  
Vol 24 (17) ◽  
pp. 1905-1911 ◽  
Author(s):  
Maria Luz Fernandez ◽  
Minu Sara Thomas ◽  
Bruno S. Lemos ◽  
Diana M. DiMarco ◽  
Amanda Missimer ◽  
...  

Background: Telomerase Activator 65 (TA-65), a compound extracted from Astragalus membranaceus has been used in Chinese traditional medicine for extending lifespan. Scarce information exists on the effects of TA-65 on parameters of metabolic syndrome (MetS). Methods: We recruited 40 patients with MetS to determine the effects of TA-65 on dyslipidemias, hypertension, and oxidative stress in this at-risk population. The study was a double-blind, randomized crossover design in which patients were allocated to consume either 16 mg daily of a TA-65 supplement or a placebo for 12 weeks. Following a 3-week washout, participants were allocated to the alternate treatment for an additional 12 weeks. Anthropometric and biological markers were measured at the end of each treatment. Plasma lipids, glucose, CReactive Protein (CRP), liver enzymes, and glycosylated hemoglobin were measured using a Cobas c-111. Inflammatory cytokines were measured by Luminex technology and markers of oxidative stress by the use of spectroscopy. Results: Compared to the placebo period, HDL cholesterol (HDL-C) was higher while body mass index, waist circumference, and the LDL/HDL ratio were lower (p < 0.05) during TA-65 treatment. In addition, plasma tumor necrosis factor-α (TNF-α) was lower during the TA-65 period (p< 0.05). Positive correlations were observed in changes between the placebo and the TA-65 periods in HDL-C and CRP (r = -0.511, p < 0.01), alanine aminotransferase (r = -0.61, p < 0.001) and TNF-α (r = -0.550, p < 0.001) suggesting that the favorable changes observed in HDL were associated with decreases in inflammation. Conclusion: TA-65 improved key markers of cardiovascular disease risk, which were also associated with reductions in inflammation.


2018 ◽  
Vol 19 (11) ◽  
pp. 3349 ◽  
Author(s):  
Jin Namkoong ◽  
Dale Kern ◽  
Helen Knaggs

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.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Masayuki Sugimoto ◽  
Hidenori Arai ◽  
Yukinori Tamura ◽  
Toshinori Murayama ◽  
Koh Ono ◽  
...  

Mulberry leaf (ML) is commonly used to feed silkworms. Previous study showed that ML ameliorates atherosclerosis. However, its mechanism is not completely understood. Because dysregulated production of adipocytokines is involved in the development of the metabolic syndrome and cardiovascular disease, we examined the effect of ML on the production of adipocytokines and metabolic disorders related to the metabolic syndrome, and compared its effect with that of a PPARγ agonist, pioglitazone (Pio). By treating obese diabetic db/db mice with ML, Pio, and their combination, we investigated the mechanism by which they improve metabolic disorders. In this study, db/+m (lean control) and db/db mice were fed a standard diet with or without 3% (w/w) ML and/or 0.01% (w/w) Pio for 12 weeks from 9 weeks of age. At the end of the experiment we found that ML decreased plasma glucose and triglyceride by 32% and 30%, respectively. Interestingly, administration of ML in addition to Pio showed additive effects; further 40% and 30% reduction in glucose and triglyceride compared with Pio treatment, respectively. Moreover, administration of ML in addition to Pio suppressed the body weight increase by Pio treatment and reduced visceral/subcutaneous fat ratio by 20% compared with control db/db mice. Importantly, ML treatment increased expression of adiponectin in white adipose tissue (WAT) by 40%, which was only found in db/db mice, not in control db/+m mice. Combination of ML and Pio increased plasma adiponectin concentrations by 25% and its expression in WAT by 17% compared with Pio alone. In contrast, ML decreased expression of TNF-α and MCP-1 by 25% and 20%, respectively, and the addition of Pio resulted in a further decrease of these cytokines by about 45%. To study the mechanism, we examined the role of oxidative stress. ML decreased the amount of lipid peroxides by 43% and the expression of NADPH oxidase subunits in WAT, which was consistent with the results of TNF-α and MCP-1. Thus our results indicate that ML ameliorates adipocytokine dysregulation by inhibiting oxidative stress in WAT of obese mice, and that ML may have a potential for the treatment of the metabolic syndrome as well as reducing adverse effects of Pio.


Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1609
Author(s):  
Hung Manh Phung ◽  
Sullim Lee ◽  
Sukyung Hong ◽  
Sojung Lee ◽  
Kiwon Jung ◽  
...  

Similar to other organs, the skin undergoes a natural aging process. Moreover, constant direct exposure to environmental stresses, including ultraviolet irradiation, causes the signs of skin aging to appear rather early. Reactive oxygen species (ROS) and inflammatory responses accelerate skin damage in extrinsic aging. In this study, we aimed to investigate the skin protective effects of polymethoxyflavones found in Kaempferia parviflora against oxidative stress and inflammation-induced damage in human dermal fibroblasts (HDFs) stimulated by tumor necrosis factor-α (TNF-α). The experimental data identified 5,7,4′ trimethoxyflavone (TMF) as the most potent constituent in preventing TNF-α-induced HDF damage among the tested compounds and it was not only effective in inhibiting matrix metalloproteinase-1 (MMP-1) production but also in stimulating collagen, type I, and alpha 1 (COLIA1) expression. TMF suppressed TNF-α-stimulated generation of ROS and pro-inflammatory mediators, such as cyclooxygenase-2 (COX-2), interleukin (IL)-1β, and IL-6 in HDFs. TMF also inhibited the pathways regulating fibroblast damage, including mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1), and nuclear factor-kappa B (NF-κB). In conclusion, TMF may be a potential agent for preventing skin aging and other dermatological disorders associated with oxidative stress and inflammation.


2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S78-S79
Author(s):  
Dorothy M Supp ◽  
Jennifer M Hahn ◽  
Christopher M Lloyd ◽  
Kelly A Combs ◽  
Viki B Swope ◽  
...  

Abstract Introduction Engineered skin substitutes (ESS) were developed to meet the need for prompt wound closure in patients with large full thickness burns. ESS containing autologous fibroblasts and keratinocytes were shown to provide stable wound closure in burn patients, but are limited by hypopigmentation. DNA damage caused by ultraviolet (UV) radiation is a known risk factor for development of skin cancer. In normal human skin, epidermal melanocytes provide pigmentation, helping to shield skin from UV-induced DNA damage. The current study investigated inclusion of human melanocytes (hM) and their role in the response of ESS to UV light in vivo. Methods Primary cells were isolated from skin of healthy de-identified human donors with IRB approval. Three groups of ESS were prepared with fibroblasts and keratinocytes, +/- hM, and were grafted orthotopically to immunodeficient mice: ESS without hM; ESS with light skin-derived (Caucasian) hM (ESS+hML); and ESS with dark skin-derived (African American) hM (ESS+hMD). After 8 weeks in vivo, grafts were irradiated with 135 mJ/cm2 UV, and mice were euthanized after 2 or 24 hours; non-UV treated mice served as controls. Pigmentation and erythema were measured with a Mexameter. Melanocytes and cyclobutane pyrimidine dimers (CPDs) were quantified by immunostaining with anti-TYRP1 and anti-CPD antibodies, respectively, followed by image analysis (Nikon Elements). Statistical analyses (SigmaPlot) utilized t-test or one-way ANOVA; P&lt; 0.05 was considered significant. Results At 8 weeks post-grafting, mean hM density in ESS+hML and ESS+hMD was not significantly different from normal human skin samples. Pigmentation (in Mexameter units) before UV irradiation was significantly different among groups (ESS+hMD &gt; ESS+hML &gt; ESS no hM). UV irradiation did not increase erythema in any group, but resulted in significantly increased pigmentation in ESS+hML and ESS+hMD at 2 hours, but not 24 hours, post-UV. CPDs, the most prevalent form of UV-induced DNA damage, were significantly elevated 24 hours post-UV in ESS without hM. DNA damage was significantly lower 24 hours post-UV in ESS+hML and ESS+hMD compared with ESS without hM. No differences in DNA damage were observed between ESS+hML and ESS+hMD. Conclusions Pigmentation of ESS+hML and ESS+hMD in vivo varied according to the skin phototype of the hM donor, with no difference in melanocyte density, which was similar to normal human skin. Inclusion of either light or dark hM decreased UV-induced DNA damage, suggesting that hM in ESS play a photoprotective role, as in normal human skin. Applicability of Research to Practice Protection against UV-induced DNA damage may reduce the risk of skin cancer in patients grafted with ESS containing melanocytes.


PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e85158 ◽  
Author(s):  
Carine Laurent ◽  
Alexandre Leduc ◽  
Ivannah Pottier ◽  
Virginie Prévost ◽  
François Sichel ◽  
...  

2017 ◽  
Vol 72 (1) ◽  
pp. 11-16 ◽  
Author(s):  
E. S. Prokudina ◽  
L. N. Maslov ◽  
V. V. Ivanov ◽  
I. D. Bespalova ◽  
D. S. Pismennyi ◽  
...  

It is established that oxidative stress induces insulin resistance of adipocytes, increases secretion leptin, IL-6, TNF-α by adipocytes. Adiponectin secretion by adipocytes is reduced after the action of reactive oxygen species. Metabolic syndrome contributes to oxidative stress in adipose tissue, on the one hand due to the activation of production of reactive oxygen species by adipocyte NADPH-oxidase, and on the other hand by reducing the antioxidant defense adipocytes. It is found that obesity itself can induce oxidative stress. Chronic stress, glucocorticoids, mineralocorticoids, angiotensin-II, TNF-α play an important role in the pathogenesis of oxidative stress of adipocytes. Metformin remains the cure for the treatment of insulin resistance. The positive results in the treatment of metabolic syndrome by losartan were obtained. Antioxidants and flavonoids exhibit a positive impact on the course of the experimental metabolic syndrome.


Sign in / Sign up

Export Citation Format

Share Document