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:
- Publication Date:
- 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.
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
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.
@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}
}
https://doi.org/10.1016/j.celrep.2016.07.088
Web of Science
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
Nucleolar expansion and elevated protein translation in premature aging
journal, August 2017
- Buchwalter, Abigail; Hetzer, Martin W.
- Nature Communications, Vol. 8, Issue 1