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

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:
Grant/Contract Number:
AC0576RL01830; AC05-76RL0 1830
Type:
Published Article
Journal Name:
Cell Reports
Additional Journal Information:
Journal Volume: 16; Journal Issue: 11; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Research Org:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1389085
Alternate Identifier(s):
OSTI ID: 1335860

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., 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}
}