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Title: FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans

Abstract

Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. But, lowering translational efficiency extends rather than shortens the lifespan in C. elegans. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditiselegans) and mass spectrometry. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, whereas others remained unchanged, signifying that longevity is not supported by high protein turnover. We found that this slowdown was most prominent for translation-related and mitochondrial proteins. Conversely, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged. The slowdown of protein dynamics and decreased abundance of the translational machinery may point to the importance of anabolic attenuation in lifespan extension, as suggested by the hyperfunction theory.

Authors:
 [1];  [2];  [1];  [1];  [1];  [2];  [3];  [1]
  1. Ghent Univ. (Belgium). Lab. for Aging Physiology and Molecular Evolution
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Biological Sciences Division
  3. Ghent Univ. (Belgium). Lab. for Aging Physiology and Molecular Evolution; Catholic Univ. of Leuven (Belgium). Lab. for Functional Genomics and Proteomics
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1389085
Grant/Contract Number:
AC0576RL01830; AC05-76RL0 1830
Resource Type:
Journal Article: Published Article
Journal Name:
Cell Reports
Additional Journal Information:
Journal Volume: 16; Journal Issue: 11; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Dhondt, Ineke, Petyuk, Vladislav A., Cai, Huaihan, Vandemeulebroucke, Lieselot, Vierstraete, Andy, Smith, Richard D., Depuydt, Geert, and Braeckman, Bart  P.. FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans. United States: N. p., 2016. Web. doi:10.1016/j.celrep.2016.07.088.
Dhondt, Ineke, Petyuk, Vladislav A., Cai, Huaihan, Vandemeulebroucke, Lieselot, Vierstraete, Andy, Smith, Richard D., Depuydt, Geert, & Braeckman, Bart  P.. FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans. United States. doi:10.1016/j.celrep.2016.07.088.
Dhondt, Ineke, Petyuk, Vladislav A., Cai, Huaihan, Vandemeulebroucke, Lieselot, Vierstraete, Andy, Smith, Richard D., Depuydt, Geert, and Braeckman, Bart  P.. 2016. "FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans". United States. doi:10.1016/j.celrep.2016.07.088.
@article{osti_1389085,
title = {FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans},
author = {Dhondt, Ineke and Petyuk, Vladislav A. and Cai, Huaihan and Vandemeulebroucke, Lieselot and Vierstraete, Andy and Smith, Richard D. and Depuydt, Geert and Braeckman, Bart  P.},
abstractNote = {Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. But, lowering translational efficiency extends rather than shortens the lifespan in C. elegans. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditiselegans) and mass spectrometry. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, whereas others remained unchanged, signifying that longevity is not supported by high protein turnover. We found that this slowdown was most prominent for translation-related and mitochondrial proteins. Conversely, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged. The slowdown of protein dynamics and decreased abundance of the translational machinery may point to the importance of anabolic attenuation in lifespan extension, as suggested by the hyperfunction theory.},
doi = {10.1016/j.celrep.2016.07.088},
journal = {Cell Reports},
number = 11,
volume = 16,
place = {United States},
year = 2016,
month = 9
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1016/j.celrep.2016.07.088

Citation Metrics:
Cited by: 2works
Citation information provided by
Web of Science

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  • Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. But, lowering translational efficiency extends rather than shortens the lifespan in C. elegans. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditiselegans) and mass spectrometry. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, whereas others remained unchanged, signifying that longevity is not supported by high protein turnover. We found that this slowdown wasmore » most prominent for translation-related and mitochondrial proteins. Conversely, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged. The slowdown of protein dynamics and decreased abundance of the translational machinery may point to the importance of anabolic attenuation in lifespan extension, as suggested by the hyperfunction theory.« less
  • Cellular protein quality can be maintained by proteolytic elimination of damaged proteins and replacing them with newly synthesized copies, a process called protein turnover (Ward, 2000). Protein turnover rates have been estimated using SILAC (stable isotope labeling by amino acids in cell culture) in prokaryotes and eukaryotes. The last decade has witnessed a growing interest in the analysis of whole-organism proteome dynamics in metazoans using the same approach (Claydon and Beynon, 2012). In recent work, SILAC was applied to monitor protein synthesis throughout life in adult Caenorhabditis elegans (Vukoti et al., 2015) and to investigate food intake (Gomez-Amaro et al.,more » 2015« less
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