Metabonomic investigations of aging and caloric restriction in a life-long dog study

Long-term restriction of energy intake without malnutrition is a robust intervention that has been shown to prolong life and delay age-related morbidity. A H-1 NMR-based metabonomic strategy was used to monitor 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 be predominantly influenced by age. Urinary excretion of creatinine increased with age, reaching a maximum between ages 5 and 9 years and declining thereafter. Excretion of mixed glycoproteins was noted at earlier ages, which may be a reflection of growth patterns. In addition, consistent metabolic variation 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 of aromatic metabolites and aliphatic amine compounds. This analysis allowed the metabolic response to two different physiological processes to be monitored throughout the lifetime of the canine population and 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. Keywords: metabonomics center dot aging center dot restricted diet center dot multivariate data analysis center dot H-1 NMR spectroscopy