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      William J. Cunliffe Scientific Awards. Characteristics and pathomechanisms of endogenously aged skin.

      1 ,
      Dermatology (Basel, Switzerland)
      S. Karger AG

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          Abstract

          The skin, being in direct contact with several environmental factors (e.g. UV irradiation), does not only undergo endogenous aging, which has to do with the 'biological clock' of the skin cells per se, but also exogenous aging. While exogenous skin aging has been extensively studied, the pathomechanisms of endogenous skin aging remain far less clear. Endogenous skin aging reflects reduction processes, which are common in internal organs. These processes include cellular senescence and decreased proliferative capacity, decrease in cellular DNA repair capacity and chromosomal abnormalities, loss of telomeres, point mutations of extranuclear mtDNA, oxidative stress and gene mutations. As a consequence, aged skin in nonexposed areas shows typical characteristics including fine wrinkles, dryness, sallowness and loss of elasticity. Recent data have illustrated that lack of hormones occurring with age may also contribute to the aging phenotype. Improvement of epidermal skin moisture, elasticity and skin thickness, enhanced production of surface lipids, reduction of wrinkle depth, restoration of collagen fibers and increase of the collagen III/I ratio have been reported after hormone replacement therapy or local estrogen treatment in postmenopausal women. Furthermore, an in vitro model of endogenous skin aging consisting of human SZ95 sebocytes which were incubated under a hormone-substituted environment illustrated that hormones at age- and sex-specific levels were able to alter the development of cells by regulating their transcriptome. In conclusion, among other factors the hormone environment plays a distinct role in the generation of aged skin.

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          Most cited references65

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            Genetic pathways that regulate ageing in model organisms.

            Searches for genes involved in the ageing process have been made in genetically tractable model organisms such as yeast, the nematode Caenorhabditis elegans, Drosophila melanogaster fruitflies and mice. These genetic studies have established that ageing is indeed regulated by specific genes, and have allowed an analysis of the pathways involved, linking physiology, signal transduction and gene regulation. Intriguing similarities in the phenotypes of many of these mutants indicate that the mutations may also perturb regulatory systems that control ageing in higher organisms.
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              Positional cloning of the Werner's syndrome gene.

              Werner's syndrome (WS) is an inherited disease with clinical symptoms resembling premature aging. Early susceptibility to a number of major age-related diseases is a key feature of this disorder. The gene responsible for WS (known as WRN) was identified by positional cloning. The predicted protein is 1432 amino acids in length and shows significant similarity to DNA helicases. Four mutations in WS patients were identified. Two of the mutations are splice-junction mutations, with the predicted result being the exclusion of exons from the final messenger RNA. One of the these mutations, which results in a frameshift and a predicted truncated protein, was found in the homozygous state in 60 percent of Japanese WS patients examined. The other two mutations are nonsense mutations. The identification of a mutated putative helicase as the gene product of the WS gene suggests that defective DNA metabolism is involved in the complex process of aging in WS patients.
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                Author and article information

                Journal
                Dermatology (Basel)
                Dermatology (Basel, Switzerland)
                S. Karger AG
                1421-9832
                1018-8665
                2007
                : 214
                : 4
                Affiliations
                [1 ] Laboratory for Biogerontology, Dermato-Pharmacology and Dermato-Endocrinology, Institute of Clinical Pharmacology and Toxicology, Charité Universitatsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
                Article
                000100890
                10.1159/000100890
                17460411
                517ec0cb-80c3-4861-9ff4-aafb10945fd9
                History

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