Abstract:There are many theories of aging and parameters that influence lifespan, including genetic instability, telomerase activity and oxidative stress. The role of caloric restriction, metabolism and insulin and insulin-like growth factor-1 signaling in the process of aging is especially well conserved throughout evolution. These latter factors interact with each other, the former factors and histone deacetylases of the SIR family in a complex interaction to influence lifespan.
“…60 Presumably, this can be ascribed to accelerated autophagy. 11,61 Calorie restriction also prolongs life and this, too, has been ascribed to increased autophagy.…”
Section: Defective Insulin Signaling Autophagy and Lifespanmentioning
Macroautophagy is a vacuolar, self-digesting mechanism responsible for the removal of long-lived proteins and damaged organelles by the lysosome. The discovery of the ATG genes has provided key information about the formation of the autophagosome, and about the role of macroautophagy in allowing cells to survive during nutrient depletion and/or in the absence of growth factors. Two connected signaling pathways encompassing class-I phosphatidylinositol 3-kinase and (mammalian) target of rapamycin play a central role in controlling macroautophagy in response to starvation. However, a considerable body of literature reports that macroautophagy is also a cell death mechanism that can occur either in the absence of detectable signs of apoptosis (via autophagic cell death) or concomitantly with apoptosis. Macroautophagy is activated by signaling pathways that also control apoptosis. The aim of this review is to discuss the signaling pathways that control macroautophagy during cell survival and cell death.
“…60 Presumably, this can be ascribed to accelerated autophagy. 11,61 Calorie restriction also prolongs life and this, too, has been ascribed to increased autophagy.…”
Section: Defective Insulin Signaling Autophagy and Lifespanmentioning
Macroautophagy is a vacuolar, self-digesting mechanism responsible for the removal of long-lived proteins and damaged organelles by the lysosome. The discovery of the ATG genes has provided key information about the formation of the autophagosome, and about the role of macroautophagy in allowing cells to survive during nutrient depletion and/or in the absence of growth factors. Two connected signaling pathways encompassing class-I phosphatidylinositol 3-kinase and (mammalian) target of rapamycin play a central role in controlling macroautophagy in response to starvation. However, a considerable body of literature reports that macroautophagy is also a cell death mechanism that can occur either in the absence of detectable signs of apoptosis (via autophagic cell death) or concomitantly with apoptosis. Macroautophagy is activated by signaling pathways that also control apoptosis. The aim of this review is to discuss the signaling pathways that control macroautophagy during cell survival and cell death.
“…Přitom v živočišné říši se jedná o naprosto fyziologický jev, typický pro období růstů, dospívání i pro těhotné ženy. Podobné nálezy se týkají nejen subkmene obratlovců, ale dokonce i jiných živočišných kmenů (42,89). Inzulinovou rezistenci lze i interpretovat jako selektivní odpověď, jak tkáně či orgány reagují na inzulin.…”
Section: Inzulinová Rezistence U Kriticky Nemocnýchunclassified
“…Reduced activity of the insulin/IGF1 pathway was sufficient but not strictly required to extend lifespan in a variety of organisms including worms, flies and mice. 51 Animal experiments indicated that the inverse relationship existing between these two pathways (inhibition of PI3K/ Akt and activation of AMPK) represents an essential intracellular switch for transducing the inhibitory effect of dietary energy restriction on mammary carcinogenesis. 52 Among the several or contributing to the onset of diseases have not been reported to date in FoxO3A locus, except for a chromosomal translocation, t(6; 11), found in a few cases of acute myeloid leukemia, which involves a fusion between MLL and FoxO3A.…”
Section: The Ampk-foxo Axis: Balancing Nutrient Sensing and Healthspamentioning
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