Proteome-wide Changes in Protein Turnover Rates in C. elegans Models of Longevity and Age-Related Disease.
The balance between protein synthesis and protein breakdown is a major determinant of protein homeostasis, and loss of protein homeostasis is one of the hallmarks of aging. Here we describe pulsed SILAC-based experiments to estimate proteome-wide turnover rates of individual proteins. We applied this method to determine protein turnover rates in Caenorhabditis elegans models of longevity and Parkinson's disease, using both developing and adult animals. Whereas protein turnover in developing, long-lived daf-2(e1370) worms is about 30% slower than in controls, the opposite was observed in day 5 adult worms, in which protein turnover in the daf-2(e1370) mutant is twice as fast as in controls. In the Parkinson's model, protein turnover is reduced proportionally over the entire proteome, suggesting that the protein homeostasis network has a strong ability to adapt. The findings shed light on the relationship between protein turnover and healthy aging.
Center for Molecular Medicine, Molecular Cancer Research Section, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Marieke
M
Visscher
Center for Molecular Medicine, Molecular Cancer Research Section, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Sasha
S
De Henau
Center for Molecular Medicine, Molecular Cancer Research Section, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Mattheus H E
MHE
Wildschut
Center for Molecular Medicine, Molecular Cancer Research Section, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Robert M
RM
van Es
Laboratory for Aging Physiology and Molecular Evolution, Biology Department, Ghent University, Proeftuinstraat 86 N1, 9000 Ghent, Belgium.
Ineke
I
Dhondt
European Research Institute for the Biology of Aging, University Medical Centre Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.
Helen
H
Michels
Center for Molecular Medicine, Molecular Cancer Research Section, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Patrick
P
Kemmeren
European Research Institute for the Biology of Aging, University Medical Centre Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.
Ellen A
EA
Nollen
Laboratory for Aging Physiology and Molecular Evolution, Biology Department, Ghent University, Proeftuinstraat 86 N1, 9000 Ghent, Belgium.
Bart P
BP
Braeckman
Center for Molecular Medicine, Molecular Cancer Research Section, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Boudewijn M T
BMT
Burgering
Center for Molecular Medicine, Molecular Cancer Research Section, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands. Electronic address: h.r.vos-3@umcutrecht.nl.
Harmjan R
HR
Vos
Center for Molecular Medicine, Molecular Cancer Research Section, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands. Electronic address: t.b.dansen@umcutrecht.nl.
Tobias B
TB
Dansen
D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004194:Disease; D004195:Disease Models, Animal; D063990:Gene Ontology; D007328:Insulin / Q000378:metabolism; D007553:Isotope Labeling; D008136:Longevity; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000473:pathology; D020543:Proteome / Q000378:metabolism*; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D007328:Insulin; D020543:Proteome; D013002:Somatomedins
Caenorhabditis elegans; age-related disease; aging; protein homeostasis; protein turnover; pulsed SILAC; quantitative proteomics