Calcium Signaling in Aging
With the rapid increase in the aging population, the compromised immune system with progressive age will become an important public health issue of the 21st century. Age-related changes of the immune system contribute to the increased susceptibility of elderly persons to infectious disease, vaccine failure, neurodegenerative disorders and possibly autoimmunity and cancer. For that reason a better understanding of immunosenescence, and the development of new strategies to counteract it, are essential for prolonging healthy life by preventing infectious diseases and thereby improving the quality of life in later years.
Our research focuses mainly on the function and maintenance of the adaptive (CD8+, CD4+), as well as the innate immune system (monocytes, macrophages, microglia), in the light of ageing with a special focus on calcium as a second messenger.
Calcium signals are essential for regulating a broad spectrum of physiological processes. In cells of the immune system, calcium signals are necessary for diverse cellular functions including differentiation, proliferation, effector function, and gene transcription. For monocytes and monocyte-derived cells like macrophages and microglia, calcium is furthermore mandatory for sufficient production of reactive oxygen species and phagocytosis.
The major route of calcium influx in human lymphocytes is through store-operated calcium entry (SOCE), mediated by calcium release-activated calcium channels (Icrac). The suppression of SOCE in human T cells results in immune deficiency and autoimmune diseases. SOCE is controlled by the interaction of stromal interaction molecules (STIM1/STIM2) in the endoplasmic reticulum with CRAC channels in the plasma membrane (Orai 1/2/3).
Our main objectives are to characterize the molecular components of calcium signaling/homeostasis in aging immune cells and their functional relevance.
Therefore we utilize a broad range of methods include electrophysiological, molecular, biochemical, microscopic and pharmacological approaches.
