Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers

Nutrient depletion, which is one of the physiological triggers of autophagy, results in the depletion of intracellular acetyl coenzyme A (AcCoA) coupled to the deacetylation of cellular proteins. We surmise that there are 3 possibilities to mimic these effects, namely (i) the depletion of cytosolic...

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Autores principales: Mariño, Guillermo, Pietrocola, Federico, Madeo, Frank, Kroemer, Guido
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502795/
https://www.ncbi.nlm.nih.gov/pubmed/25484097
http://dx.doi.org/10.4161/auto.36413
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author Mariño, Guillermo
Pietrocola, Federico
Madeo, Frank
Kroemer, Guido
author_facet Mariño, Guillermo
Pietrocola, Federico
Madeo, Frank
Kroemer, Guido
author_sort Mariño, Guillermo
collection PubMed
description Nutrient depletion, which is one of the physiological triggers of autophagy, results in the depletion of intracellular acetyl coenzyme A (AcCoA) coupled to the deacetylation of cellular proteins. We surmise that there are 3 possibilities to mimic these effects, namely (i) the depletion of cytosolic AcCoA by interfering with its biosynthesis, (ii) the inhibition of acetyltransferases, which are enzymes that transfer acetyl groups from AcCoA to other molecules, mostly leucine residues in cellular proteins, or (iii) the stimulation of deacetylases, which catalyze the removal of acetyl groups from leucine residues. There are several examples of rather nontoxic natural compounds that act as AcCoA depleting agents (e.g., hydroxycitrate), acetyltransferase inhibitors (e.g., anacardic acid, curcumin, epigallocatechin-3-gallate, garcinol, spermidine) or deacetylase activators (e.g., nicotinamide, resveratrol), and that are highly efficient inducers of autophagy in vitro and in vivo, in rodents. Another common characteristic of these agents is their capacity to reduce aging-associated diseases and to confer protective responses against ischemia-induced organ damage. Hence, we classify them as “caloric restriction mimetics” (CRM). Here, we speculate that CRM may mediate their broad health-improving effects by triggering the same molecular pathways that usually are elicited by long-term caloric restriction or short-term starvation and that imply the induction of autophagy as an obligatory event conferring organismal, organ- or cytoprotection.
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spelling pubmed-45027952015-12-18 Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers Mariño, Guillermo Pietrocola, Federico Madeo, Frank Kroemer, Guido Autophagy Editor's Corner Nutrient depletion, which is one of the physiological triggers of autophagy, results in the depletion of intracellular acetyl coenzyme A (AcCoA) coupled to the deacetylation of cellular proteins. We surmise that there are 3 possibilities to mimic these effects, namely (i) the depletion of cytosolic AcCoA by interfering with its biosynthesis, (ii) the inhibition of acetyltransferases, which are enzymes that transfer acetyl groups from AcCoA to other molecules, mostly leucine residues in cellular proteins, or (iii) the stimulation of deacetylases, which catalyze the removal of acetyl groups from leucine residues. There are several examples of rather nontoxic natural compounds that act as AcCoA depleting agents (e.g., hydroxycitrate), acetyltransferase inhibitors (e.g., anacardic acid, curcumin, epigallocatechin-3-gallate, garcinol, spermidine) or deacetylase activators (e.g., nicotinamide, resveratrol), and that are highly efficient inducers of autophagy in vitro and in vivo, in rodents. Another common characteristic of these agents is their capacity to reduce aging-associated diseases and to confer protective responses against ischemia-induced organ damage. Hence, we classify them as “caloric restriction mimetics” (CRM). Here, we speculate that CRM may mediate their broad health-improving effects by triggering the same molecular pathways that usually are elicited by long-term caloric restriction or short-term starvation and that imply the induction of autophagy as an obligatory event conferring organismal, organ- or cytoprotection. Taylor & Francis 2014-12-18 /pmc/articles/PMC4502795/ /pubmed/25484097 http://dx.doi.org/10.4161/auto.36413 Text en © 2014 The Author(s). Published with license by Taylor & Francis http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Editor's Corner
Mariño, Guillermo
Pietrocola, Federico
Madeo, Frank
Kroemer, Guido
Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers
title Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers
title_full Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers
title_fullStr Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers
title_full_unstemmed Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers
title_short Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers
title_sort caloric restriction mimetics: natural/physiological pharmacological autophagy inducers
topic Editor's Corner
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502795/
https://www.ncbi.nlm.nih.gov/pubmed/25484097
http://dx.doi.org/10.4161/auto.36413
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