How aging impacts skin biomechanics: a multiscale study in mice.
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ABSTRACT:
SUBMITTER: Lynch B
PROVIDER: S-EPMC5653787 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Soft connective tissues such as skin, tendon or cornea are made of about 90% of extracellular matrix proteins, fibrillar collagens being the major components. Decreased or aberrant collagen synthesis generally results in defective tissue mechanical properties as the classic form of Elhers-Danlos syndrome (cEDS). This connective tissue disorder is caused by mutations in collagen V genes and is mainly characterized by skin hyperextensibility. To investigate the relationship between the microstructure of normal and diseased skins and their macroscopic mechanical properties, we imaged and quantified the microstructure of dermis of ex vivo murine skin biopsies during uniaxial mechanical assay using multiphoton microscopy. We used two genetically-modified mouse lines for collagen V: a mouse model for cEDS harboring a Col5a2 deletion (a.k.a. pN allele) and the transgenic K14-COL5A1 mice which overexpress the human COL5A1 gene in skin. We showed that in normal skin, the collagen fibers continuously align with stretch, generating the observed increase in mechanical stress. Moreover, dermis from both transgenic lines exhibited altered collagen reorganization upon traction, which could be linked to microstructural modifications. These findings show that our multiscale approach provides new crucial information on the biomechanics of dermis that can be extended to all collagen-rich soft tissues.
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Project description:The world population is aging and no country is immune to the consequences. We are not aware of any country-specific skin aging risk factors data for the Mongolian people. Thus, we aimed to study the risk factors associated with skin aging in the Mongolian population. A population-based cross-sectional study of 2720 study participants 18 years of age and older was performed evaluating the severity of skin aging based on cutaneous microtopography. Questionnaire data and skin physiological measurements were obtained. The odds ratios for skin aging grades associated with risk factors were estimated using ordinal logistic regression. Study participant's mean age was 45 years, ranging from 18 to 87. After adjustment for known risk factors, skin aging was associated with demographic risk factors such as increasing age (aOR = 1.19, 95% CI 1.18-1.20), living in an urban area (aOR = 1.31, 95% CI 1.12-1.55) and lifestyle factors including being a smoker (aOR = 1.32, 95% CI 1.09-1.61), having a higher body mass index (aOR = 1.04, 95% CI 1.02-1.06) and higher levels of sun exposure time (aOR = 1.03, 95% CI 1.00-1.06) were significantly associated with higher skin aging grades. Having dry (aOR = 1.94, 95% CI 1.45-2.59) and combination skin (aOR = 1.62, 95% CI 1.22-2.16) types were also independent risk factors associated with skin aging. Having very low skin surface moisture at the T-zone (aOR = 2.10, 95% CI 1.42-3.11) was significantly related to skin aging. Older age, urban living and toxic working conditions were independent demographic risk factors related to skin aging. Smoking, higher BMI, greater levels of sun exposure were significant lifestyle risk factors. Having a skin type other than normal was a physiologic risk factor for skin aging.
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Project description:Introduction: Aging has many effects on the cardiovascular system, including changes in structure (aortic composition, and thus stiffening) and function (increased proximal blood pressure, and thus cardiac afterload). Mouse models are often used to gain insight into vascular aging and mechanisms of disease as they allow invasive assessments that are impractical in humans. Translation of results from murine models to humans can be limited, however, due to species-specific anatomical, biomechanical, and hemodynamic differences. In this study, we built fluid-solid-interaction (FSI) models of the aorta, informed by biomechanical and imaging data, to compare wall mechanics and hemodynamics in humans and mice at two equivalent ages: young and older adults. Methods: For the humans, 3-D computational models were created using wall property data from the literature as well as patient-specific magnetic resonance imaging (MRI) and non-invasive hemodynamic data; for the mice, comparable models were created using population-based properties and hemodynamics as well as subject-specific anatomies. Global aortic hemodynamics and wall stiffness were compared between humans and mice across age groups. Results: For young adult subjects, we found differences between species in pulse pressure amplification, compliance and resistance distribution, and aortic stiffness gradient. We also found differences in response to aging between species. Generally, the human spatial gradients of stiffness and pulse pressure across the aorta diminished with age, while they increased for the mice. Conclusion: These results highlight key differences in vascular aging between human and mice, and it is important to acknowledge these when using mouse models for cardiovascular research.
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Project description:This study aimed to determine the effect of topically applied Laminaria polysaccharide (LP) on skin aging. We applied ointment containing LP (10, 25, and 50??g/g) or vitamin E (10??g/g) to the dorsal skin of aging mice for 12 months and young control mice for 4 weeks. Electron microscopy analysis of skin samples revealed that LP increased dermal thickness and skin collagen content. Tissue inhibitor of metalloprotease- (TIMP-) 1 expression was upregulated while that of matrix metalloproteinase- (MMP-) 1 was downregulated in skin tissue of LP-treated as compared to untreated aging mice. Additionally, phosphorylation of c-Jun N-terminal kinase (JNK) and p38 was higher in aging skin than in young skin, while LP treatment suppressed phospho-JNK expression. LP application also enhanced the expression of antioxidative enzymes in skin tissue, causing a decrease in malondialdehyde levels and increases in superoxide dismutase, catalase, and glutathione peroxidase levels relative to those in untreated aging mice. These results indicate that LP inhibits MMP-1 expression by preventing oxidative stress and JNK phosphorylation, thereby delaying skin collagen breakdown during aging.
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Project description:The aging process deleteriously alters the structure and function of dermal collagen. These alterations result in thinning, fragility, wrinkles, laxity, impaired wound healing, and a microenvironment conducive to cancer. However, the key factors responsible for these changes have not been fully elucidated, and relevant models for the study of skin aging progression are lacking. CCN1, a secreted extracellular matrix‒associated matricellular protein, is elevated in dermal fibroblasts in aged human skin. Toward constructing a mouse model to study the key factors involved in skin-aging progression, we demonstrate that transgenic mice, with selective expression of CCN1 in dermal fibroblasts (COL1A2-CCN1), display accelerated skin dermal aging. The aged phenotype in COL1A2-CCN1 mice resembles aged human dermis: the skin is wrinkled and the dermis is thin and composed of loose, disorganized, and fragmented collagen fibrils. These dermal alterations reflect reduced production of collagen due to impaired TGFβ signaling and increased expression of matrix metalloproteinases driving the induction of c-Jun/activator protein-1. Importantly, similar mechanisms drive human dermal aging. Taken together, the data demonstrate that elevated expression of CCN1 by dermal fibroblasts functions as a key mediator of dermal aging. The COL1A2-CCN1 mouse model provides a novel tool for understanding and studying the mechanisms of skin aging and age-related skin disorders.
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Project description:BackgroundSuture materials and techniques are frequently evaluated in ex vivo studies by comparing tensile strengths. However, the direct measurement techniques to obtain the tensile forces in canine skin are not available, and, therefore, the conditions suture lines undergo is unknown. A soft elastomeric capacitor is used to monitor deformation in the skin over time by sensing strain. This sensor was applied to a sample of canine skin to evaluate its capacity to sense strain in the sample while loaded in a dynamic material testing machine. The measured strain of the sensor was compared with the strain measured by the dynamic testing machine. The sample of skin was evaluated with and without the sensor adhered.ResultsIn this study, the soft elastomeric capacitor was able to measure strain and a correlation was made to stress using a modified Kelvin-Voigt model for the canine skin sample. The sensor significantly increases the stiffness of canine skin when applied which required the derivation of mechanical models for interpretation of the results.ConclusionsFlexible sensors can be applied to canine skin to investigate the inherent biomechanical properties. These sensors need to be lightweight and highly elastic to avoid interference with the stress across a suture line. The sensor studied here serves as a prototype for future sensor development and has demonstrated that a lightweight highly elastic sensor is needed to decrease the effect on the sensor/skin construct. Further studies are required for biomechanical characterization of canine skin.
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Project description:Mechanical interactions between flowing and coagulated blood (thrombus) are crucial in dictating the deformation and remodeling of a thrombus after its formation in hemostasis. We propose a fully-Eulerian, three-dimensional, phase-field model of thrombus that is calibrated with existing in vitro experimental data. This phase-field model considers spatial variations in permeability and material properties within a single unified mathematical framework derived from an energy perspective, thereby allowing us to study effects of thrombus microstructure and properties on its deformation and possible release of emboli under different hemodynamic conditions. Moreover, we combine this proposed thrombus model with a particle-based model which simulates the initiation of the thrombus. The volume fraction of a thrombus obtained from the particle simulation is mapped to an input variable in the proposed phase-field thrombus model. The present work is thus the first computational study to integrate the initiation of a thrombus through platelet aggregation with its subsequent viscoelastic responses to various shear flows. This framework can be informed by clinical data and potentially be used to predict the risk of diverse thromboembolic events under physiological and pathological conditions.
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