Functioning methionine-S-sulfoxide reductases A and B are present in human skin. (73/367)

Methionine residues in the structure of proteins and peptides are especially sensitive to oxidation by hydrogen peroxide (H(2)O(2)) yielding both the (R) and (S) diastereomers of methionine sulfoxide. This commentary shows that both diastereomers of methionine sulfoxide (R and S) can be repaired in the human epidermis by methionine sulfoxide reductases A and B, respectively.  (+info)

Concepts in a multiprong approach to photoaging. (74/367)

Photoaging is a multisystem degenerative process that involves the skin and the skin support systems, including the bone, cartilage, and subcutaneous compartments. These structures provide the architectural support for the dermis, epidermis, and stratum corneum. A multiprong approach to photoaging involves reversing the undesirable changes in each of these structures. Dermatologists should become adept at treating all of the visible manifestations of photoaging.  (+info)

The epidemiology of nevi and signs of skin aging in the adult general population: Results of the KORA-survey 2000. (75/367)

Nevi can approximate the melanoma risk and demographic changes will increase the meaning of signs of skin aging (SSA). However, little is known about the epidemiology of nevi and SSA in the general adult population. We aimed to estimate the prevalence and age distribution of common and atypical nevi and SSA as well as gender differences in a large population-based sample. Within the Cooperative Health Research in the Augsburg Region (KORA) in Germany, a population-based survey was performed. Data were gathered by interview and the number of pigmented lesions and presence of SSA were obtained by dermatological examination. A total of 2,823 adults (mean age 49 years, 50% women) participated (response 67%). Most subjects (60.3%) exhibited 11 to 50 common nevi and 5.2% had at least one atypical nevus. 51.9% were diagnosed with elastosis (Cutis rhomboidalis nuchae, 18.3%; Morbus Favre Racouchot 1.4%). Ephelides were seen in 16%, lentigines solaris in 62.4%, and lentigines seniles in 33.2%. All signs of skin aging increased significantly with age and so did lentigines solaris, seniles, and actinic keratoses. In contrast, common and atypical nevi and ephelides decreased significantly with age. Signs of skin aging are frequent and increase, in contrast to common and atypical nevi, with age.  (+info)

Decreased collagen production in chronologically aged skin: roles of age-dependent alteration in fibroblast function and defective mechanical stimulation. (76/367)

Reduced synthesis of collagen types I and III is characteristic of chronologically aged skin. The present report provides evidence that both cellular fibroblast aging and defective mechanical stimulation in the aged tissue contribute to reduced collagen synthesis. The reduction in collagen synthesis due to fibroblast aging was demonstrated by a lower in vitro production of type I procollagen by dermal fibroblasts isolated from skin of young (18 to 29 years) versus old (80+ years) individuals (82 +/- 16 versus 56 +/- 8 ng/ml; P < 0.05). A reduction in mechanical stimulation in chronologically aged skin was inferred from morphological, ultrastructural, and fluorescence microscopic studies. These studies, comparing dermal sections from young and old individuals, demonstrated a greater percentage of the cell surface attached to collagen fibers (78 +/- 6 versus 58 +/- 8%; P < 0.01) and more extensive cell spreading (1.0 +/- 0.3 vs. 0.5 +/- 0.3; P < 0.05) in young skin compared with old skin. These features are consistent with a lower level of mechanical stimulation on the cells in old versus young skin. Based on the findings presented here, we conclude that reduced collagen synthesis in chronologically aged skin reflects at least two different underlying mechanisms: cellular fibroblast aging and a lower level of mechanical stimulation.  (+info)

UVB-irradiated human keratinocytes and interleukin-1alpha indirectly increase MAP kinase/AP-1 activation and MMP-1 production in UVA-irradiated dermal fibroblasts. (77/367)

BACKGROUND: Solar ultraviolet (UV) irradiation induces the production of matrix metalloproteinases (MMPs) by activating cellular signalling transduction pathways. MMPs are responsible for the degradation and/or inhibition of synthesis of collagenous extracellular matrix in connective tissues. We mimicked the action of environmental ultraviolet on skin and investigated the effects of UVB-irradiated human keratinocytes HaCaT and IL-1alpha on mitogen activated protein (MAP) kinase activation, c-Jun and c-Fos (AP-1 is composed of Jun and Fos proteins) mRNA expression and MMP-1 production in UVA-irradiated dermal fibroblasts. METHODS: Following UVA irradiation, the culture medium of fibroblasts was replaced by culture medium from UVB-irradiated HaCaT, or replaced by the complete culture medium with interleukin (IL)-1alpha. MAP kinase activity expression in fibroblasts was detected by Western blot. c-Jun and c-Fos mRNA expressions were determined by reverse transcriptional polymerase chain reaction (RT-PCR); MMP-1 production in culture medium was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Culture medium from UVB-irradiated keratinocytes increased MAP kinase activity and c-Jun mRNA expression in UVA-irradiated fibroblasts. IL-1alpha increased MAP kinase activity and c-Jun mRNA expression, IL-1alpha also increased c-Fos mRNA expression. Both culture media from UVB-irradiated human keratinocytes and externally applied IL-1alpha increased MMP-1 production in UVA-irradiated fibroblasts. CONCLUSIONS: UVB-irradiated keratinocytes and IL-1alpha indirectly promote MMP-1 production in UVA-irradiated fibroblasts by increasing MAP kinase/AP-1 activity. IL-1 may play an important role in the paracrine activation and dermal collagen excessive degradation leading to skin photoaging.  (+info)

Smoking related COPD and facial wrinkling: is there a common susceptibility? (78/367)

BACKGROUND: Cigarette smoking causes accelerated facial wrinkling and predisposes to chronic obstructive pulmonary disease (COPD). However, it has long been recognised that there is a subgroup of susceptible smokers who are at increased risk of developing airflow obstruction. We have tested the hypothesis that there is a common susceptibility for the development of COPD and facial wrinkling in cigarette smokers. METHODS: One hundred and forty nine current and ex-smokers were recruited from a family based study of COPD genetics, 68 (45.6%) of whom fulfilled the definition of COPD. 124 (83.2%) had no or minor facial wrinkling (Daniell /=IV). Generalised estimating equations were used to adjust for familial correlations between related individuals and the potential confounding effects of age and pack years smoked. RESULTS: Forced expiratory volume in 1 second (FEV(1)) was significantly lower in those with wrinkles than in those without (mean difference in FEV(1) % predicted -13.7%, 95% CI -27.5 to 0.0, p = 0.05) and facial wrinkling was associated with a substantially increased risk of COPD (adjusted OR 5.0, 95% CI 1.3 to 18.5, p<0.02). The Daniell score correlated with the extent of emphysema on the CT scan (p<0.05) and facial wrinkling was also associated with a greater risk of more extensive emphysema (adjusted OR 3.0, 95% CI 1.0 to 9.3, p = 0.05). CONCLUSION: Facial wrinkling is associated with COPD in smokers, and both disease processes may share a common susceptibility. Facial wrinkling in smokers may therefore be a biomarker of susceptibility to COPD.  (+info)

Mouse homologue of skin-specific retroviral-like aspartic protease involved in wrinkle formation. (79/367)

Retroviral proteases are encoded in the retroviral genome and are responsible for maturation and assembly of infectious virus particles. A number of retroviral protease sequences with retroviral elements are integrated in every eukaryotic genome as endogenous retroviruses. Recently, retroviral-like aspartic proteases that were not embedded within endogenous retroviral elements were identified throughout the eukaryotic and prokaryotic genomes. However, the physiological role of this novel protease family, especially in mammals, is not known. During the high throughput in situ hybridization screening of mouse epidermis, as a granular layer-expressing clone, we identified a mouse homologue of SASPase (Skin ASpartic Protease), a recently identified retroviral-like aspartic protease. We detected and purified the endogenous 32-kDa (mSASP32) and 15-kDa (mSASP15) forms of mSASP from mouse stratum corneum extracts and determined their amino acid sequences. Next, we bacterially produced recombinant mSASP15 via autoprocessing of GST-mSASP32. Purified recombinant mSASP15 cleaved a quenched fluorogenic peptide substrate, designed from the autoprocessing site for mSASP32 maximally at pH 5.77, which is close to the pH of the epidermal surface. Finally, we generated mSASP-deficient mice that at 5 weeks of age showed fine wrinkles that ran parallel on the lateral trunk without apparent epidermal differentiation defects. These results indicate that the retroviral-like aspartic protease, SASPase, is involved in prevention of fine wrinkle formation via activation in a weakly acidic stratum corneum environment. This study provides the first evidence that retroviral-like aspartic protease is functionally important in mammalian tissue organization.  (+info)

Elevated cysteine-rich 61 mediates aberrant collagen homeostasis in chronologically aged and photoaged human skin. (80/367)

Alterations of human skin connective tissue structure and function are prominent features of chronological aging and solar UV irradiation-induced premature aging (photoaging). These skin connective tissue abnormalities result, in part, from reduced synthesis and elevated degradation of type I collagen, the major structural protein in skin. Here, we report that cysteine-rich 61 (CYR61/CCN1), a novel mediator of collagen homeostasis, is predominantly expressed in human skin connective tissue and is significantly elevated in fibroblasts in chronologically aged (80+ years) and photoaged human skin in vivo. In cultured human skin fibroblasts, elevated CYR61 expression substantially reduces type I procollagen and concurrently increases matrix metalloproteinase-1 (MMP-1), which initiates fibrillar collagen degradation. Elevated CYR61 caused down-regulation of transforming growth factor-beta type II receptor mRNA and protein levels, thereby impairing the transforming growth factor-beta pathway, which reduced type I procollagen and raised MMP-1 expression. Furthermore, elevated CYR61 induced transcription factor activator protein-1 (AP-1), which functions to stimulate MMP-1 expression. Thus, elevated expression of CYR61 in human skin fibroblasts acts through multiple pathways to cause alterations of collagen homeostasis similar to those pathways observed in aged human skin in vivo. These data identify CYR61 as a pivotal regulator of collagen production and degradation in aged and photoaged human skin.  (+info)