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. However, 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. This slowdown was most prominent for translation-related and mitochondrial proteins. In contrast, 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.
Laboratory for Aging Physiology and Molecular Evolution, Biology Department, Ghent University, Proeftuinstraat 86 N1, 9000 Ghent, Belgium.
Ineke
I
Dhondt
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
Vladislav A
VA
Petyuk
Laboratory for Aging Physiology and Molecular Evolution, Biology Department, Ghent University, Proeftuinstraat 86 N1, 9000 Ghent, Belgium.
Huaihan
H
Cai
Laboratory for Aging Physiology and Molecular Evolution, Biology Department, Ghent University, Proeftuinstraat 86 N1, 9000 Ghent, Belgium.
Lieselot
L
Vandemeulebroucke
Laboratory for Aging Physiology and Molecular Evolution, Biology Department, Ghent University, Proeftuinstraat 86 N1, 9000 Ghent, Belgium.
Andy
A
Vierstraete
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
Richard D
RD
Smith
Laboratory for Aging Physiology and Molecular Evolution, Biology Department, Ghent University, Proeftuinstraat 86 N1, 9000 Ghent, Belgium; Laboratory for Functional Genomics and Proteomics, Department of Biology, KU Leuven, Naamsestraat 59, 3000 Leuven, Belgium.
Geert
G
Depuydt
Laboratory for Aging Physiology and Molecular Evolution, Biology Department, Ghent University, Proeftuinstraat 86 N1, 9000 Ghent, Belgium. Electronic address: bart.braeckman@ugent.be.
Bart P
BP
Braeckman
D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006207:Half-Life; D007425:Intracellular Membranes / Q000378:metabolism; D007553:Isotope Labeling; D008247:Lysosomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D014176:Protein Biosynthesis; D040901:Proteomics; D015203:Reproducibility of Results; D013312:Stress, Physiological; D013347:Subcellular Fractions / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; D051858:Forkhead Transcription Factors; D009124:Muscle Proteins; C108831:daf-16 protein, C elegans
(15)N-metabolic labeling; Caenorhabditis elegans; FOXO/DAF-16; aging; daf-2 mutant; protein turnover