08:00 - 09:30 Uhr
Löwengebäude HS XIII
Vorsitz: Bartling, Babett (Halle (Saale)); Eckers, Anna (Düsseldorf)
Modification of Aging
E. Carmeli*; B. Imam; E. Kodesh
*Department of Physical Therapy, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa/IL;
Objective: Moderate exercise training has numerous benefits on physical function, cognition and mental health. However, the effect of exercise training on reducing anxiety measured by change in motor spatial behavior has not been investigated. The objective of this study was to examine the effects of moderate exercise training on anxiety-related behaviors that result in increased locomotion and physical activity.
Method: Old (17 months) female mice (n=6), C57B6 were allocated to either a sedentary or a running group that underwent 12 weeks of treadmill running (20 minutes/day, 6 days/week). Anxiety-related behavior was assessed using an Open Field Test.
Results: a) Moderate exercise training resulted in an increased locomotion in the running group compared to the sedentary group. The running mice a) entered the 'inner zone' of the open field more frequently; b) exhibited higher movement velocity within the arena; c) travelled a longer distance; and d) spent less time at the corners of the open field.
Conclusion: The results indicate the beneficial effects of moderate exercise training on reducing anxiety-related behavior and triggering spatial behaviors in an Open Field Test among old mice.
T. O. Kleine; C. Löwer
Institut für Laboratoriumsmedizin und Pathobiochemie, Univeristätsklinikum Giessen und Marburg, Philipps-Universität Marburg, Marburg;
Cellular immune surveillance of human central nervous system (CNS) is mainly carried out with lymphocytes in cerebrospinal fluid (CSF). CSF lymphocytes are a mixture of blood and lymph lymphocytic cells: Although blood-brain barrier in CNS capillaries/venules and blood-CSF barrier in choroid plexus lock lymphocyte transfer from blood into brain and CSF completely, blood pressure (RR) drains few blood lymphocytes through holes in CNS circumventricular organs into ventricle (V) CSF and some lymph with lymph lymphocytes reflux into spinal CSF, when CSF is drained out along nerve roots into spinal lymph. RR is the stressor of blood lymphocytes to transfer into V CSF; respiration, pulse waves, muscular exertion, change of posture, coughing are stressors of lymph lymphocytes during to- and fro-motions of spinal CSF to re-flux into spinal CSF.
RR increases somewhat with age; but reduced CSF production in healthy aging CNS may annul the cranial RR stressor effect.
The effect of aging on the spinal stressors is examined in lumbar CSF and peripheral venous blood (PVB) sample pairs of healthy controls:
Lymphocytes and their subsets were analyzed with cell counting and FACS analysis (Becton Dickinson): With increasing age, counts of blood lymphocyte, of T cells CD3+, helper/inducer CD3+4+ and cytotoxic/supressor CD3+8+ subsets, natural killer cells CD16+56+3-, and B lymphocytes CD19+3- decrease in PVB. The negative aging effect on blood lymphocytes and their subsets appears to be transmitted to CSF lymphocytes and their 5 subsets decreasing in lumbar CSF with increasing age of healthy persons.
Deduction: The positive effect of RR as stressor of transfer of blood lymphocyte into V CSF and the positive effects of the spinal stressors on reflux of lymph lymphocytes into spinal CSF appear to be ineffective on immune surveillance of human aging CNS with lymphocytes, because negative aging effect on the synthesis of blood and lymph lymphocytes dominates as a generalized aging effect on lymphocyte production and turnover in CSF, blood and lymph of aging healthy humans. DNA lesions besides somatic mutations in aging lymphocytes are discussed to be general causes of impaired immune surveillance in aging healthy humans; DNA damage appears to be more effective than somatic mutations.
K. Koch; S. Havermann; C. Büchter; W. Wätjen
Biofunctionality of secondary plant compounds, Institute of Agriculture and Nutritional Science, Martin-Luther University Halle-Wittenberg, Halle (Saale);
A diet rich in vegetables, fruits and grains is associated with protective effects against various age-related diseases. Bioactive substances like fiber and secondary plant compounds seem to contribute to these health effects. While the biological mechanism of fiber has been extensively studied the mode of action of secondary plant compounds is mostly unknown due to their structural variety. Especially polyphenols like flavonoids, coumarins and lignans possess interesting chemical properties, e.g. their radical scavenging activity. There is also evidence that these compounds can mediate redox-sensitive signaling pathways. In order to investigate cellular pathways in vivo we used the nematode C. elegans as a model organism which provides a multitude on advantages e.g. short lifespan, simplicity in laboratory maintenance and the availability genetic modified strains. The aim of this study was to identify polyphenols which are able to modulate stress-sensitive signaling pathways and hence biological parameters of C. elegans. For this purpose we studied the effect of the plant compounds on the translocation of typical stress activated transcription factors DAF-16 (FoxO homologue) and SKN-1 (Nrf2 homologue) by means of transgene C. elegans strains. Further on we analyzed biological characteristics that can be modulated by these pathways: stress resistance, reactive oxygen (ROS) accumulation and the life span. For the thermal stress resistance and the ROS accumulation we used semi-automated fluorescence assays while life span was determined by prodding the nematode periodically in order the monitor the survival.
In conclusion we were able to show that C. elegans is an appropriate model organism to study the effect of secondary plant compounds on redox-sensitive signaling pathways that are associated with stress resistance and ageing.
S. Pötzsch; M. L. Dalgalarrondo1; B. N. D. Bakan1; D. Marion1; V. Somoza2; G. Stangl3; R.-E. Silber; A. Simm4; A. Navarrete Santos
Universitätsklinik und Poliklinik für Innere Medizin, Herz- und Thoraxchirurgie, Universitätsklinikum, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale); 1 INRA - B.I.A., Nantes/F; 2 Research Platform for Molecular Food Science, University of Vienna, Vienna/A; 3 Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Halle/Saale; 4 Zentrum für Medizinische Grundlagenforschung (ZMG), Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale);
Objective: Free radicals and oxidative stress are important factors in the biology of aging and responsible for the development of age-related diseases. One way to reduce the formation of free radicals is to boost the antioxidative system by nutrition. Heat treatment of food promote the Maillard reaction which is responsible for their characteristic color and taste. During the Maillard reaction reducing sugars react with proteins in a non-enzymatic way leading to the formation of advanced glycation end products (AGEs). As an AGE-rich source our group used bread crust (BCE) to investigate the effect of AGEs on the antioxidant defense.
Methods: It is well known that the NF-kB pathway is activated by treatment of cells with AGEs. Therefore for stimulation with the BCE we used the macrophage reporter cell line RAW/NF-kB/SEAPorter™. Amino acid analysis and LC-MS/MS by Orbitrap Velo was used to determine the bioactive compounds in the soluble BCE. The radical scavenging effect was conducted by the DPPH-assay.
Results: BCE induced the NF-kB pathway in RAW/NF-kB/SEAPorter™ cells and also showed a concentration-dependent antioxidative capacity. With the LC/MS and amino acid analyses, we identified the presence of gliadin in BCE confirmed by using specific gliadin antibodies. By immunoprecipitation (IP) with an antibody against gamma-gliadin and western blot probing against the AGE carboxymethyllysine (CML) the presence of AGE-gliadin in BCE was confirmed. Stimulation of the RAW/NF-kB/SEAPorter™ cells with the gamma-gliadin depleted fractions did not activate the NF-kB pathway.
Conclusion: CML-modified gliadin in the BCE is a bioactive compound of the bread crust which is responsible for the antioxidative capacity and for the induction of the NF-kB pathway in mouse macrophages.
S. Jakob; C. Goy; J. Altschmied; J. Haendeler
Molekulare Alternsforschung, an der Universität Düsseldorf gGmbH, Leibniz-Institut für Umweltmedizinische Forschung, Düsseldorf;
Caffeine is one of the most widely used drug in the world. Recent studies have shown a protective effect of caffeine on the cardiovascular system. We have shown that concentrations of caffeine, which can be measured in the serum after moderate coffee consumption (5 cups, 50 µM) enhanced the migratory capacity of endothelial cells (EC). Therefore, we wanted to identify the molecular link between caffeine, mitochondrial energy metabolism and migration.
Surprisingly, we found that caffeine induces the translocation of p27/Kip1 (p27), originally identified as a cell cycle inhibitor, into the mitochondria. Reducing p27 with siRNA inhibited caffeine induced migration. Next we cloned mitochondrially targeted p27 (mitop27) and nuclear targeted p27 (nucp27) to investigate the effects of p27 localization on mitochondrial energy metabolism and migration. Whereas overexpression of nucp27 decreased basal migration, overexpression of mitop27 increased migration, mitochondrial ATP production and integrity of the mitochondrial membrane potential. Along the same lines, only overexpression of mitop27, but not nuclear p27, rescued the complete loss of migratory capacity induced by knockdown of p27. To investigate the connection of caffeine and p27 also in vivo, we performed microarray analysis of hearts from wildtype and p27-deficient mice treated with caffeine (0.1 % = 50 µM serum concentration) in their drinking water for 10 days to exclude central nervous system effects. Caffeine induced expression of several genes involved in mitochondrial biogenesis and mitochondrial energy metabolism only in wildtype mice demonstrating a crucial role for p27 in enhanced mitochondrial function.
Therefore, caffeine seems to have a dual function, a short term translocation of p27 to the mitochondria improving their function and in the long run a change in gene expression leading to mitochondrial biogenesis.