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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9450999 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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