76 research outputs found

    Chronological aging leads to apoptosis in yeast

    Get PDF
    During the past years, yeast has been successfully established as a model to study mechanisms of apoptotic regulation. However, the beneficial effects of such a cell suicide program for a unicellular organism remained obscure. Here, we demonstrate that chronologically aged yeast cultures die exhibiting typical markers of apoptosis, accumulate oxygen radicals, and show caspase activation. Age-induced cell death is strongly delayed by overexpressing YAP1, a key transcriptional regulator in oxygen stress response. Disruption of apoptosis through deletion of yeast caspase YCA1 initially results in better survival of aged cultures. However, surviving cells lose the ability of regrowth, indicating that predamaged cells accumulate in the absence of apoptotic cell removal. Moreover, wild-type cells outlast yca1 disruptants in direct competition assays during long-term aging. We suggest that apoptosis in yeast confers a selective advantage for this unicellular organism, and demonstrate that old yeast cells release substances into the medium that stimulate survival of the clone

    Nucleocytosolic depletion of the energy metabolite acetyl-coenzyme a stimulates autophagy and prolongs lifespan.

    Get PDF
    Healthy aging depends on removal of damaged cellular material that is in part mediated by autophagy. The nutritional status of cells affects both aging and autophagy through as-yet-elusive metabolic circuitries. Here, we show that nucleocytosolic acetyl-coenzyme A (AcCoA) production is a metabolic repressor of autophagy during aging in yeast. Blocking the mitochondrial route to AcCoA by deletion of the CoA-transferase ACH1 caused cytosolic accumulation of the AcCoA precursor acetate. This led to hyperactivation of nucleocytosolic AcCoA-synthetase Acs2p, triggering histone acetylation, repression of autophagy genes, and an age-dependent defect in autophagic flux, culminating in a reduced lifespan. Inhibition of nutrient signaling failed to restore, while simultaneous knockdown of ACS2 reinstated, autophagy and survival of ach1 mutant. Brain-specific knockdown of Drosophila AcCoA synthetase was sufficient to enhance autophagic protein clearance and prolong lifespan. Since AcCoA integrates various nutrition pathways, our findings may explain diet-dependent lifespan and autophagy regulation

    Structural changes to resorbable calcium phosphate bioceramic aged <i>in vitro</i>

    Get PDF
    This work investigates the effect of mammalian cell culture conditions on 3D printed calcium phosphate scaffolds. The purpose of the studies presented was to characterise the changes in scaffold properties in physiologically relevant conditions. Differences in crystal morphologies were observed between foetal bovine serum-supplemented media and their unsupplemented analogues, but not for supplemented media containing tenocytes. Scaffold porosity was found to increase for all conditions studied, except for tenocyte-seeded scaffolds. The presence of tenocytes on the scaffold surface inhibited any increase in scaffold porosity in the presence of extracellular matrix secreted by the tenocytes. For acellular conditions the presence or absence of sera proteins strongly affected the rate of dissolution and the distribution of pore diameters within the scaffold. Exposure to high sera protein concentrations led to the development of significant numbers of sub-micron pores, which was otherwise not observed. The implication of these results for cell culture research employing calcium phosphate scaffolds is discussed

    The Warburg Effect Suppresses Oxidative Stress Induced Apoptosis in a Yeast Model for Cancer

    Get PDF
    BACKGROUND: Otto Warburg observed that cancer cells are often characterized by intense glycolysis in the presence of oxygen and a concomitant decrease in mitochondrial respiration. Research has mainly focused on a possible connection between increased glycolysis and tumor development whereas decreased respiration has largely been left unattended. Therefore, a causal relation between decreased respiration and tumorigenesis has not been demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: For this purpose, colonies of Saccharomyces cerevisiae, which is suitable for manipulation of mitochondrial respiration and shows mitochondria-mediated cell death, were used as a model. Repression of respiration as well as ROS-scavenging via glutathione inhibited apoptosis and conferred a survival advantage during seeding and early development of this fast proliferating solid cell population. In contrast, enhancement of respiration triggered cell death. CONCLUSION/SIGNIFICANCE: Thus, the Warburg effect might directly contribute to the initiation of cancer formation--not only by enhanced glycolysis--but also via decreased respiration in the presence of oxygen, which suppresses apoptosis

    Europa im Geflecht der Welt

    Get PDF
    Der Band dokumentiert Vorträge und Workshops der internationalen Abschlusstagung des DFG-Schwerpunktprogrammes 1173 „Integration und Desintegration der Kulturen im europäischen Mittelalter“, die Ende Mai 2011 in Berlin stattgefunden hat. Bei der Arbeit im Schwerpunktprogramm hatte sich gezeigt, wie schwierig es ist, Europa im geographischen und historischen Sinne vom Mittelmeerraum mit Nordafrika und Vorder¬asien zu trennen. Daher wurden die Grenzen des mittelalterlichen Europa bewusst überschritten und auch die Geschichte weiter entfernter Länder in den Blick genommen. Als thematischer Schwerpunkt boten sich in diesem Zusammenhang Migrationen an. Migrationen sind ja ein globales Phäno¬men, das an allen Orten und zu allen Zeiten immer wieder die Geschichte der Menschheit prägt und dabei unvermeidlich – selbst in der scheinbaren Isolation einer „Diaspora“ oder „Parallelgesellschaft“ – zu transkulturellen Verflechtungen führt. Fremde und einheimische Gruppen und Individuen werden in neue soziale Umgebungen gerückt und Kontakte oder Konflikte zwischen ihnen erzeugt. Wo aber das jeweilige Leben gegeneinander abgeschottet werden soll, verliert Kultur ihre Inno¬vations¬kraft und versteinert die Gesellschaft. Mit dem Sachthema der „Migrationen“ und mit einem Blick weit über Europa hinaus, bis nach Amerika, Japan und ins südliche Afrika, wird der Übergang von einer eurozentrierten Mittelalterforschung zu einer transdisziplinären Mediävistik in globalen Zusammenhängen markiert
    corecore