Metabonomic Investigations of Aging and Caloric Restriction in a Life-Long Dog Study
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- 作者：Yulan Wang ; Dennis Lawler ; Brian Larson ; Ziad Ramadan ; Sunil Kochhar ; Elaine Holmes ; Jeremy K. Nicholson
- 刊名：Journal of Proteome Research
- 出版年：2007
- 出版时间：May 2007
- 年：2007
- 卷：6
- 期：5
- 页码：1846 - 1854
- 全文大小：2733K
- 年卷期：v.6,no.5(May 2007)
- ISSN：1535-3907
文摘
Long-term restriction of energy intake without malnutrition is a robust intervention that has been shownto prolong life and delay age-related morbidity. A 1H NMR-based metabonomic strategy was used tomonitor urinary metabolic profiles throughout the lifetimes of control-fed and diet-restricted dogs.Urinary metabolic trajectories were constructed for each dog, and metabolic variation was found to bepredominantly influenced by age. Urinary excretion of creatinine increased with age, reaching amaximum between ages 5 and 9 years and declining thereafter. Excretion of mixed glycoproteins wasnoted at earlier ages, which may be a reflection of growth patterns. In addition, consistent metabolicvariation related to diet was also characterized, and energy-associated metabolites, such as creatine,1-methylnicotinamide, lactate, acetate, and succinate, were depleted in urine from diet-restricted dogs.Both aging and diet restriction altered activities of the gut microbiotia, manifested by variation ofaromatic metabolites and aliphatic amine compounds. This analysis allowed the metabolic responseto two different physiological processes to be monitored throughout the lifetime of the canine populationand may form part of a strategy to monitor and reduce the impact of age related diseases in the dog,as well as providing more general insights into extension of longevity in higher mammals.