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Rates of protein synthesis are maintained in brain but reduced in skeletal muscle during dietary sulfur amino acid restriction

Dietary interventions such as sulfur amino acid restriction (SAAR) target multiple drivers of aging, and show promise for preventing or delaying the onset of chronic diseases. SAAR promotes metabolic health and longevity in laboratory animals. The effects of SAAR on proteostasis remain relatively un...

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Autores principales: Martinez, Wenceslao, Zhang, Qian, Linden, Melissa A., Schacher, Nate, Darvish, Sanna, Mirek, Emily T., Levy, Jordan L., Jonsson, William O., Anthony, Tracy G., Hamilton, Karyn L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9450999/
https://www.ncbi.nlm.nih.gov/pubmed/36091469
http://dx.doi.org/10.3389/fragi.2022.975129
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author Martinez, Wenceslao
Zhang, Qian
Linden, Melissa A.
Schacher, Nate
Darvish, Sanna
Mirek, Emily T.
Levy, Jordan L.
Jonsson, William O.
Anthony, Tracy G.
Hamilton, Karyn L.
author_facet Martinez, Wenceslao
Zhang, Qian
Linden, Melissa A.
Schacher, Nate
Darvish, Sanna
Mirek, Emily T.
Levy, Jordan L.
Jonsson, William O.
Anthony, Tracy G.
Hamilton, Karyn L.
author_sort Martinez, Wenceslao
collection PubMed
description Dietary interventions such as sulfur amino acid restriction (SAAR) target multiple drivers of aging, and show promise for preventing or delaying the onset of chronic diseases. SAAR promotes metabolic health and longevity in laboratory animals. The effects of SAAR on proteostasis remain relatively unexplored. We previously reported that SAAR promotes mitochondrial proteostatic maintenance, despite suppression of global protein synthesis, in two peripheral tissues, the liver and skeletal muscle. However, the brain, a tissue vulnerable to age-related neurodegenerative diseases due to the loss of proteostasis, has not been thoroughly studied. Therefore, we sought to reveal proteostatic responses in the brains of mice fed SAAR for 35 days. Here, we demonstrate that male C57Bl/6J mice fed two levels of SAAR maintained rates of protein synthesis in all sub-cellular fractions of the pre-frontal cortex. In comparison, rates of skeletal muscle protein synthesis in SAAR fed mice were slower than control-fed mice. To gain mechanistic insight, we examined several key nutrient/energy sensitive signaling proteins: AMP-activated protein kinase (AMPK), eukaryotic initiation factor 2 (eIF2), and ribosomal protein S6 (rpS6). SAAR had minimal to modest effects on the total abundance and phosphorylation of these proteins in both tissues. Our results indicate that the pre-frontal cortex in brain is resistant to perturbations in protein synthesis in mice fed SAAR, unlike skeletal muscle, which had a reduction in global protein synthesis. The results from this study demonstrate that proteostatic control in brain is of higher priority than skeletal muscle during dietary SAAR.
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spelling pubmed-94509992022-09-08 Rates of protein synthesis are maintained in brain but reduced in skeletal muscle during dietary sulfur amino acid restriction Martinez, Wenceslao Zhang, Qian Linden, Melissa A. Schacher, Nate Darvish, Sanna Mirek, Emily T. Levy, Jordan L. Jonsson, William O. Anthony, Tracy G. Hamilton, Karyn L. Front Aging Aging Dietary interventions such as sulfur amino acid restriction (SAAR) target multiple drivers of aging, and show promise for preventing or delaying the onset of chronic diseases. SAAR promotes metabolic health and longevity in laboratory animals. The effects of SAAR on proteostasis remain relatively unexplored. We previously reported that SAAR promotes mitochondrial proteostatic maintenance, despite suppression of global protein synthesis, in two peripheral tissues, the liver and skeletal muscle. However, the brain, a tissue vulnerable to age-related neurodegenerative diseases due to the loss of proteostasis, has not been thoroughly studied. Therefore, we sought to reveal proteostatic responses in the brains of mice fed SAAR for 35 days. Here, we demonstrate that male C57Bl/6J mice fed two levels of SAAR maintained rates of protein synthesis in all sub-cellular fractions of the pre-frontal cortex. In comparison, rates of skeletal muscle protein synthesis in SAAR fed mice were slower than control-fed mice. To gain mechanistic insight, we examined several key nutrient/energy sensitive signaling proteins: AMP-activated protein kinase (AMPK), eukaryotic initiation factor 2 (eIF2), and ribosomal protein S6 (rpS6). SAAR had minimal to modest effects on the total abundance and phosphorylation of these proteins in both tissues. Our results indicate that the pre-frontal cortex in brain is resistant to perturbations in protein synthesis in mice fed SAAR, unlike skeletal muscle, which had a reduction in global protein synthesis. The results from this study demonstrate that proteostatic control in brain is of higher priority than skeletal muscle during dietary SAAR. Frontiers Media S.A. 2022-08-24 /pmc/articles/PMC9450999/ /pubmed/36091469 http://dx.doi.org/10.3389/fragi.2022.975129 Text en Copyright © 2022 Martinez, Zhang, Linden, Schacher, Darvish, Mirek, Levy, Jonsson, Anthony and Hamilton. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Aging
Martinez, Wenceslao
Zhang, Qian
Linden, Melissa A.
Schacher, Nate
Darvish, Sanna
Mirek, Emily T.
Levy, Jordan L.
Jonsson, William O.
Anthony, Tracy G.
Hamilton, Karyn L.
Rates of protein synthesis are maintained in brain but reduced in skeletal muscle during dietary sulfur amino acid restriction
title Rates of protein synthesis are maintained in brain but reduced in skeletal muscle during dietary sulfur amino acid restriction
title_full Rates of protein synthesis are maintained in brain but reduced in skeletal muscle during dietary sulfur amino acid restriction
title_fullStr Rates of protein synthesis are maintained in brain but reduced in skeletal muscle during dietary sulfur amino acid restriction
title_full_unstemmed Rates of protein synthesis are maintained in brain but reduced in skeletal muscle during dietary sulfur amino acid restriction
title_short Rates of protein synthesis are maintained in brain but reduced in skeletal muscle during dietary sulfur amino acid restriction
title_sort rates of protein synthesis are maintained in brain but reduced in skeletal muscle during dietary sulfur amino acid restriction
topic Aging
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9450999/
https://www.ncbi.nlm.nih.gov/pubmed/36091469
http://dx.doi.org/10.3389/fragi.2022.975129
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