Language: Deutsch I English

Spokesperson

Prof. Dr. Karin Scharffetter-Kochanek
Klinik für Dermatologie und Allergologie
Universität Ulm
Maienweg 12
89081 Ulm

Head

Prof. Dr. Hartmut Geiger
Klinik für Dermatologie und Allergologie
Universität Ulm
James Franck-Ring 11c
89081 Ulm

Project 1

Significance of manganese superoxide dismutase in extrinsic and intrinsic aging processes of the skin

Mitochondrial manganese superoxide dismutase (SOD2), which detoxifies super oxide anions, was identified as a gerontogene responsible for the regulation of aging and life-span in C. elegans and Drosophila, however, its importance in higher organisms has not been clarified. During the last funding period, we demonstrated that connective tissue specific SOD2-deficient mice exhibit a complex aging phenotype with decreased life span, kyphosis, osteoporosis, myopathy, and extreme skin atrophy, especially in the dermal connective tissue and subcutaneous fat tissue.

One main focus of our work is to clarify whether or not the observed oxidative and nitrosative damage to connective tissue of the skin causes activation of DNA damage signalling pathways, as our initial observations of increased γH2AX and p16^Ink4a expression suggest. Furthermore, we will investigate whether DNA damage signaling pathways inhibit the somatotrophin axis due to decreased secretion of insulin and insulin growth factor (IGF-1) and if this contributes to the observed aging phenotype. At least connective tissue rich tissues such as skin, muscles, bones and possibly also stem cell niches require adequate IGF-1 concentrations for proper tissue homeostasis. To further investigate these potential systemic endocrinal effects, skin from connective tissue-specific SOD2-deficient mice will be transplanted onto immune-deficient nude mice, and the aging phenotype of the transplanted skin will be compared with the skin from connective tissue-specific SOD2-deficient mice. In addition, IGF-1/insulin metabolism and glucose metabolism as well as DNA damage signalling pathways will each be evaluated for their causal relevance to the early aging phenotype.

A second, complimentary goal will be to examine whether there is damage to the stromal/mesenchymal stem cells (niches) and if this leads to blockade of dermal, adipogenic, osteogenic or chondrogenic differentiation. The elucidation of these questions will significantly improve the understanding of how systemic and local oxidative damage to connective tissue, including the stromal/mesenchymal stem cells (MSC) and parenchymal organs, contribute to extrinsic and intrinsic aging processes.

Chief Investigator

Karin Scharffetter-Kochanek, MD
Professor of Dermatology and Chair of the Department of Dermatology and Allergic Diseases
University of Ulm
Maienweg 12
89081 Ulm
Germany

Phone: +49 (0)731 500 57501
Fax: +49 (0)731 500 57502
karin.scharfetter-kochanek[at]uniklinik-ulm.de

References

List of publications from:
Karin Scharffetter-Kochanek
>> Pubmed