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

Dhondt, Ineke; Petyuk, Vladislav A.; Cai, Huaihan; Vandemeulebroucke, Lieselot; Vierstraete, Andy; Smith, Richard D.; Depuydt, Geert; Braeckman, Bart P.

doi:10.1016/j.celrep.2016.07.088

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:: Dhondt, Ineke; Petyuk, Vladislav A.; Cai, Huaihan; Vandemeulebroucke, Lieselot; Vierstraete, Andy; Smith, Richard D.; Depuydt, Geert; Braeckman, Bart P.

Publication Date:: Thu Sep 01 00:00:00 EDT 2016

Research Org.:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Org.:: USDOE

OSTI Identifier:: 1389085

Alternate Identifier(s):: OSTI ID: 1335860

Grant/Contract Number:: AC05-76RL0 1830; AC0576RL01830

Resource Type:: Published Article

Journal Name:: Cell Reports

Additional Journal Information:: Journal Name: Cell Reports Journal Volume: 16 Journal Issue: 11; Journal ID: ISSN 2211-1247

Publisher:: Elsevier

Country of Publication:: Netherlands

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.  Netherlands: N. p., 2016. 
Web.  doi:10.1016/j.celrep.2016.07.088.

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                    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.  Netherlands.  https://doi.org/10.1016/j.celrep.2016.07.088

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                    Dhondt, Ineke, Petyuk, Vladislav A., Cai, Huaihan, Vandemeulebroucke, Lieselot, Vierstraete, Andy, Smith, Richard D., Depuydt, Geert, and Braeckman, Bart P. Thu .  
"FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans".  Netherlands.  https://doi.org/10.1016/j.celrep.2016.07.088.

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@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        = {Netherlands},

  year         = {Thu Sep 01 00:00:00 EDT 2016},

  month        = {Thu Sep 01 00:00:00 EDT 2016}

}

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Works referencing / citing this record:

Accumulation of “Old Proteins” and the Critical Need for MS‐based Protein Turnover Measurements in Aging and Longevity
journal, March 2020

Basisty, Nathan; Holtz, Anja; Schilling, Birgit
PROTEOMICS, Vol. 20, Issue 5-6
DOI: 10.1002/pmic.201800403

Nucleolar expansion and elevated protein translation in premature aging
journal, August 2017

Buchwalter, Abigail; Hetzer, Martin W.
Nature Communications, Vol. 8, Issue 1
DOI: 10.1038/s41467-017-00322-z

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

Abstract

Citation Formats

Accumulation of “Old Proteins” and the Critical Need for MS‐based Protein Turnover Measurements in Aging and Longevity journal, March 2020

Nucleolar expansion and elevated protein translation in premature aging journal, August 2017

Accumulation of “Old Proteins” and the Critical Need for MS‐based Protein Turnover Measurements in Aging and Longevity
journal, March 2020

Nucleolar expansion and elevated protein translation in premature aging
journal, August 2017