Journal
JOURNAL OF PROTEOME RESEARCH
Volume 13, Issue 6, Pages 2910-2919Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr5000686
Keywords
metabolomics; metabonomics; Caenorhabditis elegans; NMR; aging; dietary restriction; PTEN; HR-MAS
Categories
Funding
- NIH National Center for Research Resources
- Association pour la Recherche sur le Cancer (ARC) [076751]
- CNRS (AO Longevite et Vieillissement)
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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 H-1 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 slcf1-(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.
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