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Karsten Gülow is Group Leader ROS signalling, is specialized in cell signalling, oxidative stress and apoptosis.
Multicellular organisms generally undergo qualitative changes within time (ageing) that are associated with progressive degeneration of biological functions, increased susceptibility to diseases, and increased probability to death within a given time period. In 1956 Harman developed the popular “free radical theory of ageing”. He stated that age-related degenerative processes to a large extent are the consequence of free radical damage. In the free radical theory of ageing reactive oxygen species (ROS) is associated with cell damage and cytotoxicity. However, accumulating evidence now suggests that ROS can act as signalling molecules. Recently, we investigated the involvement of ROS in T cell receptor (TCR) signalling. During ageing TCR signalling and ROS generation is altered in comparison to signalling processes in T cells of “young” donors. Therefore, it is important to investigate the induction of immune senescence during ageing in the context of ROS generation and maintenance of the redox balance. We found that ageing factor-1 (AF-1) has an important role as a negative regulator of the cellular redox equilibrium and is a potential inducer of enhanced stress generation in the elderly, ultimately leading to disturbed cellular function and, in the end, to deterioration of immune cell function. In our model we explain changes in cellular AF-1 expression in the involvement of alterations observed during ageing leading to the deterioration of general cellular function and malfunctioning of the immune system.
Role in SyStemAge:
Analysis of the role of the novel ageing factor-1 (AF1) in:
- Physiological ageing: Our studies will concentrate on the potential function of AF-1 as a main regulator of enhanced oxidative stress during ageing. We will consider signs of oxidative stress and senescence upon of AF-1 overexpression. We will complement the study at molecular levels, by the analysis of longevity and/or resistance to stress in AF-1 knockout or transgenic organisms, drosophila and mice
- Pathological ageing; AF-1 will also be investigated in disease condition, such as MDS. During progression of MDS a loss of proliferative HSC, and accumulation of quiescent (CD34+, CD38-), and dormant (CD34-, p57+) HSC is observed. Our preliminary results indicate that AF-1 is directly involved in physiological and pathological ageing processes.
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