Biological stress activation

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Biological stress activation

The maintenance of life is critically dependent on keeping internal milieu constant in the face of a changing environment called homeostasis. Stress is the effects of anything that seriously threatens homeostasis. The actual or perceived threat to an organism is referred to as the “stressor” and the response to the stressor is called the “stress response.” Although stress responses evolved as adaptive processes, severe, prolonged stress responses might lead to tissue damage and disease.

Metabolic stress is generally considered from the standpoint of how cells detect and respond to an insufficient supply of nutrients to meet their bioenergetic needs. However, cells also experience stress as a result of nutrient excess, during which reactive oxygen species (ROS) production exceeds that required for normal physiological responses. This may occur as a result of oncogene activation or chronic exposure to growth factors combined with high levels of nutrients. As a result, multiple mechanisms have evolved to allow cells to detect and adapt to elevated levels of intracellular metabolites, including promotion of signaling and proliferation by ROS, amino acid-dependent mTOR activation, and regulation of signaling and transcription through metabolite-sensitive protein modifications.

Damage to cellular DNA evokes a wide range of acute cellular responses that ultimately lead to delay of cell cycle progression, stimulation of DNA repair, and alteration in the expression of genes necessary for the cell's recovery and survival. Depending on the cell type and extent of damage, pathways leading to programmed cell death may be activated. All this processes are called genotoxic stress. For instance, a prominent type of DNA damage, DNA strand breaks, is generated by a variety of genotoxic agents, including ionizing radiation (IR), radiomimetic agents, and inhibitors of topoisomerases. The p53 tumor suppressor is a universal sensor of genotoxic stress that regulates the transcription of genes required for cell-cycle arrest and apoptosis.

The self-association of misfolded or damaged proteins into ordered amyloid-like aggregates is proteotoxic effect of different type of stresses such as temperature or oxidative stress. Many neurodegenerative disorders are characterized by the misfolding and subsequent aggregation of toxic proteins. Alzheimer, Parkinson, and the glutamine-encoding expansion diseases are examples of conformational disorders which show late onset symptoms of progressive neuronal dysfunction and eventual neuronal loss within certain brain regions. The disease-causing protein can adopt aberrant conformations due to age or stress which enables its aggregation and ultimate accumulation in amyloid fibrils.

Lipotoxicity is the fatty acid-induced cell injuries. It may be caused by over-nutrition and sedentary lifestyle is based on observations, where chronic exposure of non-adipose cells and tissues to elevated concentrations of fatty acids, triacylglycerols, or cholesterol triggers toxic effects; these contribute to the pathogenesis of obesity, insulin resistance, type II diabetes, and the metabolic syndrome. Interruption of triglyceride synthesis, apparently because of the formation of a pool of oversaturated intermediates, seems to be a key event in SFA-induced lipotoxicity. When lipids overaccumulate in nonadipose tissues due to overnutrition, fatty acids enter potentially dangerous pathways, such as ceramide production, which, through increased nitric oxide (NO) formation, causes apoptosis of lipid-laden cells, such as h-cells and cardiomyocytes.