title: Metabolomics analysis uncovers that dietary restriction buffers metabolic changes associated with aging in Caenorhabditis elegans.
abstract: Dietary restriction (DR) is one of the most universal means of extending lifespan. Yet, whether and how DR specifically affects the metabolic changes associated with aging is essentially unknown. Here, we present a comprehensive and unbiased picture of the metabolic variations that take place with age at the whole organism level in Caenorhabditis elegans by using (1)H high-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) analysis of intact worms. We investigate metabolic variations potentially important for lifespan regulation by comparing the metabolic fingerprint of two previously described genetic models of DR, the long-lived eat-2(ad465) and slcf-1(tm2258) worms, as single mutants or in combination with a genetic suppressor of their lifespan phenotype. Our analysis shows that significant changes in metabolite profiles precede the major physiological decline that accompanies aging and that DR protects from some of those metabolic changes. More specifically, low phosphocholine (PCho) correlates with high life expectancy. A mutation in the tumor suppressor gene PTEN/DAF-18, which suppresses the beneficial effects of DR in both C. elegans and mammals, increases both PCho level and choline kinase expression. Furthermore, we show that choline kinase function in the intestine can regulate lifespan. This study highlights the relevance of NMR metabolomic approaches for identifying potential biomarkers of aging.
authors.affiliation: Centre de RMN à très hauts champs, Institut des sciences analytiques, CNRS/ENS Lyon/UCB Lyon1 , 5 rue de la Doua, 69100 Villeurbanne, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Pontoizeau
authors.forename: Laurent
authors.initials: L
authors.lastname: Mouchiroud
authors.forename: Laurent
authors.initials: L
authors.lastname: Molin
authors.forename: Adeline
authors.initials: A
authors.lastname: Mergoud-Dit-Lamarche
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dallière
authors.forename: Pierre
authors.initials: P
authors.lastname: Toulhoat
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Elena-Herrmann
authors.forename: Florence
authors.initials: F
authors.lastname: Solari
mesh_terms: D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D031204:Caloric Restriction; D002797:Choline Kinase / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007422:Intestines / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D055432:Metabolomics; D009154:Mutation; D010767:Phosphorylcholine / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C116661:DAF-18 protein, C elegans; D010767:Phosphorylcholine; D002797:Choline Kinase