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

Journal Article · Thu Sep 01 00:00:00 EDT 2016 · Cell Reports

DOI:https://doi.org/10.1016/j.celrep.2016.07.088· OSTI ID:1389085

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

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.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE
• Grant/Contract Number: AC05-76RL0 1830; AC0576RL01830
• OSTI ID: 1389085
• Alternate ID(s): OSTI ID: 1335860
• Journal Information: Cell Reports, Journal Name: Cell Reports Vol. 16 Journal Issue: 11; ISSN 2211-1247
• Publisher: Elsevier
• Country of Publication: Netherlands
• Language: English

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59 BASIC BIOLOGICAL SCIENCES