KFO 142:  Molecular and Cellular Aging - From Mechanisms to Clinical Perspectives

• Subject Area: Medicine
• Term: from 2006 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 17771695

Aging affects different organs (organ systems) resulting in loss of function, increased morbidity and mortality. Aging is regulated by the intimate interaction of genetic (intrinsic) and environmental (extrinsic) factors with high specificity for each organ. The aim of this Clinical Research Unit is to characterise molecular mechanisms of cellular aging and to test their general relevance for the complex in vivo situation of aging in different organs. Following elucidation of basic principles, preventative and therapeutic approaches will be developed to assist healthy aging. The dense conceptual and methodical expertise within the Clinical Research Unit will be successfully applied to investigate aging of organ systems with superordinate function (immune system), with pace maker function for organismal aging (central nervous system) or with model character for aging of the connective tissue (skin). The hypothesis to be tested is whether oxidative stress with mitochondrial and nuclear DNA damage changes in signal transduction pathways, cell-cell communication and gene expression of different evolutionary conserved gerontogenes (SIRT1, FOXO3, SOD2) is of general relevance for intrinsic and extrinsic aging of the immune system, the central nervous system and the connective tissue. The Clinical Research Unit will address this central question with a variety of in vitro and in vivo systems including conditional transgenic mice with deficiencies or overexpression of antioxidative enzymes, DNA-repair enzymes, aging relevant insulin-, NF-kappaB- and FOXO1/3-pathway components, cells and biopsies from patients with premature aging syndromes and from long-lived individuals (centenarians), comparative genomic hybridisation, microarrays and bioinformatics, reconstituted in vitro transcription, proteomics, analysis of mitochondrial function, DNA-damage and repair, characterisation of thymus involution and vaccination strategies. These efforts will shed light on the mechanisms involved in the age-dependent changes of the immune system with increased incidence of infections, autoimmune diseases, of the central nervous system with degeneration of neurons, and of the connective tissue with impaired wound healing, osteoporosis, arthrosis and arteriosclerosis. The development of antioxidative strategies and mimetics of key players in aging relevant signalling pathways as well as of vaccination protocols will distinctly contribute to assist healthy aging.

• DFG Programme: Clinical Research Units

Projects

• Bedeutung der Mangansuperoxiddismutase bei extrinischen und intrinsischen Alterungsprozessen der Haut (Applicant Scharffetter-Kochanek, Karin )
• Changes in the interaction of aged hematopoietic stem cells with the bone marrow niche/stroma: implications for stem cell aging (Applicant Geiger, Hartmut )
• Die Bedeutung des FOXO3 für die neuronale Entwicklung, Alterung und Degeneration (Applicant Wirth, Thomas )
• Die Regulation muriner, anti-viraler CD8+ T-Zellantworten mit fortschreitendem Alter (Applicant Reimann, Jörg )
• Die Regulation muriner CD8+ T-Zellantworten mit fortschreitendem Alter (Applicant Schirmbeck, Reinhold )
• Die Rolle von DNA-Schäden und deren Reparatur in verschiedenen klinischen Segmenten der Alterung: Untersuchungen zur funktionellen Relevanz und prophylaktisch/therapeutischen Intervention (Applicant Berneburg, Mark-Jürgen )
• Die Rolle von Thymus-Epithelzell-Progenitoren bei der Thymus-Alterung (Applicant Rodewald, Hans-Reimer )
• Einfluss von Alterung auf die Funktion von Langerhans-Zell Vorläuferzellen und ihre Ausdifferenzierung zu Langerhans-Zellen (Applicant Weiss, Johannes Martin )
• Koordination der Klinischen Forschungsgruppe 142 (Applicant Scharffetter-Kochanek, Karin )
• Oxidativer Stress und DNA Reparatur bei der Motoneurondegeneration (Applicant Ludolph, Albert Christian )
• Untersuchungen zum Einfluss der zellulären Komposition aus gealterten und jungen Zellen auf Organerhalt und organismische Alterung (Applicant Rudolph, Karl Lenhard )
• Welche Bedeutung haben Veränderungen in der Transkriptionskontrolle für vorzeitige Alterung und Alterung im Allgemeinen (Applicant Iben, Sebastian )

• Spokesperson: Professorin Dr. Karin Scharffetter-Kochanek
• Leader: Professor Dr. Hartmut Geiger