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Axenic Culture of Caenorhabditis elegans Alters Lysosomal/Proteasomal Balance and Increases Neuropeptide Expression

Axenically cultured C. elegans show many characteristic traits of worms subjected to dietary restriction, such as slowed development, reduced fertility, and increased stress resistance. Hence, the term axenic dietary restriction (ADR) is often applied. ADR dramatically extends the worm lifespan comp...

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Autores principales: Cai, Huaihan, Wu, Ping, Vandemeulebroucke, Lieselot, Dhondt, Ineke, Rasulova, Madina, Vierstraete, Andy, Braeckman, Bart P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570027/
https://www.ncbi.nlm.nih.gov/pubmed/36232823
http://dx.doi.org/10.3390/ijms231911517
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author Cai, Huaihan
Wu, Ping
Vandemeulebroucke, Lieselot
Dhondt, Ineke
Rasulova, Madina
Vierstraete, Andy
Braeckman, Bart P.
author_facet Cai, Huaihan
Wu, Ping
Vandemeulebroucke, Lieselot
Dhondt, Ineke
Rasulova, Madina
Vierstraete, Andy
Braeckman, Bart P.
author_sort Cai, Huaihan
collection PubMed
description Axenically cultured C. elegans show many characteristic traits of worms subjected to dietary restriction, such as slowed development, reduced fertility, and increased stress resistance. Hence, the term axenic dietary restriction (ADR) is often applied. ADR dramatically extends the worm lifespan compared to other DR regimens such as bacterial dilution. However, the underlying molecular mechanisms still remain unclear. The primary goal of this study is to comprehensively investigate transcriptional alterations that occur when worms are subjected to ADR and to estimate the molecular and physiological changes that may underlie ADR-induced longevity. One of the most enriched clusters of up-regulated genes under ADR conditions is linked to lysosomal activity, while proteasomal genes are significantly down-regulated. The up-regulation of genes specifically involved in amino acid metabolism is likely a response to the high peptide levels found in axenic culture medium. Genes related to the integrity and function of muscles and the extracellular matrix are also up-regulated. Consistent down-regulation of genes involved in DNA replication and repair may reflect the reduced fertility phenotype of ADR worms. Neuropeptide genes are found to be largely up-regulated, suggesting a possible involvement of neuroendocrinal signaling in ADR-induced longevity. In conclusion, axenically cultured worms seem to rely on increased amino acid catabolism, relocate protein breakdown from the cytosol to the lysosomes, and do not invest in DNA maintenance but rather retain muscle integrity and the extracellular matrix. All these changes may be coordinated by peptidergic signaling.
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spelling pubmed-95700272022-10-17 Axenic Culture of Caenorhabditis elegans Alters Lysosomal/Proteasomal Balance and Increases Neuropeptide Expression Cai, Huaihan Wu, Ping Vandemeulebroucke, Lieselot Dhondt, Ineke Rasulova, Madina Vierstraete, Andy Braeckman, Bart P. Int J Mol Sci Article Axenically cultured C. elegans show many characteristic traits of worms subjected to dietary restriction, such as slowed development, reduced fertility, and increased stress resistance. Hence, the term axenic dietary restriction (ADR) is often applied. ADR dramatically extends the worm lifespan compared to other DR regimens such as bacterial dilution. However, the underlying molecular mechanisms still remain unclear. The primary goal of this study is to comprehensively investigate transcriptional alterations that occur when worms are subjected to ADR and to estimate the molecular and physiological changes that may underlie ADR-induced longevity. One of the most enriched clusters of up-regulated genes under ADR conditions is linked to lysosomal activity, while proteasomal genes are significantly down-regulated. The up-regulation of genes specifically involved in amino acid metabolism is likely a response to the high peptide levels found in axenic culture medium. Genes related to the integrity and function of muscles and the extracellular matrix are also up-regulated. Consistent down-regulation of genes involved in DNA replication and repair may reflect the reduced fertility phenotype of ADR worms. Neuropeptide genes are found to be largely up-regulated, suggesting a possible involvement of neuroendocrinal signaling in ADR-induced longevity. In conclusion, axenically cultured worms seem to rely on increased amino acid catabolism, relocate protein breakdown from the cytosol to the lysosomes, and do not invest in DNA maintenance but rather retain muscle integrity and the extracellular matrix. All these changes may be coordinated by peptidergic signaling. MDPI 2022-09-29 /pmc/articles/PMC9570027/ /pubmed/36232823 http://dx.doi.org/10.3390/ijms231911517 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cai, Huaihan
Wu, Ping
Vandemeulebroucke, Lieselot
Dhondt, Ineke
Rasulova, Madina
Vierstraete, Andy
Braeckman, Bart P.
Axenic Culture of Caenorhabditis elegans Alters Lysosomal/Proteasomal Balance and Increases Neuropeptide Expression
title Axenic Culture of Caenorhabditis elegans Alters Lysosomal/Proteasomal Balance and Increases Neuropeptide Expression
title_full Axenic Culture of Caenorhabditis elegans Alters Lysosomal/Proteasomal Balance and Increases Neuropeptide Expression
title_fullStr Axenic Culture of Caenorhabditis elegans Alters Lysosomal/Proteasomal Balance and Increases Neuropeptide Expression
title_full_unstemmed Axenic Culture of Caenorhabditis elegans Alters Lysosomal/Proteasomal Balance and Increases Neuropeptide Expression
title_short Axenic Culture of Caenorhabditis elegans Alters Lysosomal/Proteasomal Balance and Increases Neuropeptide Expression
title_sort axenic culture of caenorhabditis elegans alters lysosomal/proteasomal balance and increases neuropeptide expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570027/
https://www.ncbi.nlm.nih.gov/pubmed/36232823
http://dx.doi.org/10.3390/ijms231911517
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