title: Metabolome and proteome changes with aging in Caenorhabditis elegans.
abstract: To expand the understanding of aging in the model organism Caenorhabditis elegans, global quantification of metabolite and protein levels in young and aged nematodes was performed using mass spectrometry. With age, there was a decreased abundance of proteins functioning in transcription termination, mRNA degradation, mRNA stability, protein synthesis, and proteasomal function. Furthermore, there was altered S-adenosyl methionine metabolism as well as a decreased abundance of the S-adenosyl methionine synthetase (SAMS-1) protein. Other aging-related changes included alterations in free fatty acid levels and composition, decreased levels of ribosomal proteins, decreased levels of NADP-dependent isocitrate dehydrogenase (IDH1), a shift in the cellular redox state, an increase in sorbitol content, alterations in free amino acid levels, and indications of altered muscle function and sarcoplasmic reticulum Ca(2+) homeostasis. There were also decreases in pyrimidine and purine metabolite levels, most markedly nitrogenous bases. Supplementing the culture medium with cytidine (a pyrimidine nucleoside) or hypoxanthine (a purine base) increased lifespan slightly, suggesting that aging-induced alterations in ribonucleotide metabolism affect lifespan. An age-related increase in body size, lipotoxicity from ectopic yolk lipoprotein accumulation, a decline in NAD(+) levels, and mitochondrial electron transport chain dysfunction may explain many of these changes. In addition, dietary restriction in aged worms resulting from sarcopenia of the pharyngeal pump likely decreases the abundance of SAMS-1, possibly leading to decreased phosphatidylcholine levels, larger lipid droplets, and ER and mitochondrial stress. The complementary use of proteomics and metabolomics yielded unique insights into the molecular processes altered with age in C. elegans.
authors.affiliation: Department of Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, FL, USA. Electronic address: ncopes@mail.usf.edu.
authors.forename: Neil
authors.initials: N
authors.lastname: Copes
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA. Electronic address: cbedward@mail.usf.edu.
authors.forename: Clare
authors.initials: C
authors.lastname: Edwards
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA. Electronic address: chaput@mail.usf.edu.
authors.forename: Dale
authors.initials: D
authors.lastname: Chaput
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA. Electronic address: msaifee@mail.usf.edu.
authors.forename: Mariam
authors.initials: M
authors.lastname: Saifee
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA. Electronic address: iosifbarjuca@mail.usf.edu.
authors.forename: Iosif
authors.initials: I
authors.lastname: Barjuca
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA. Electronic address: dnnelson29@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nelson
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA. Electronic address: aparaggi@mail.usf.edu.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Paraggio
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA. Electronic address: patricksaad@mail.usf.edu.
authors.forename: Patrick
authors.initials: P
authors.lastname: Saad
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA. Electronic address: delipps@mail.usf.edu.
authors.forename: David
authors.initials: D
authors.lastname: Lipps
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA. Electronic address: smstevens@usf.edu.
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Stevens
authors.affiliation: Department of Biomedical Sciences, East Tennessee State University College of Medicine, Johnson City, TN, USA. Electronic address: bradshawp@etsu.edu.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Bradshaw
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D006706:Homeostasis; D013058:Mass Spectrometry; D055442:Metabolome / Q000235:genetics*; D055432:Metabolomics; D008928:Mitochondria / Q000378:metabolism; D020543:Proteome / Q000235:genetics*; D040901:Proteomics; D055948:Sarcopenia / Q000378:metabolism
chemical_list: D020543:Proteome
keywords: Aging; Ascorbate; C. elegans; Caenorhabditis; Lifespan; Metabolome; Metabolomics; Methionine; Methylation; Methyltransferase; Nitrogenous bases; Proteome; Proteomics; Purine; Pyrimidine; S-adenosyl methionine; SAMS-1; SERCA; Sorbitol