The practice of calorie restriction, eating fewer calories while still maintaining an optimal intake of nutrients, produces sweeping beneficial changes in metabolism. It produces larger short term changes in measures of health in humans than any presently available medical technology, and can extend maximum life span in laboratory animals such as mice by up to 40%. In longer lived species it seems that any extension of life becomes shorter, however, even while the short term changes in metabolism, health measures, and metabolic processes remain very similar - which is a puzzle.
Modeling aging and age-related pathologies presents a substantial analytical challenge given the complexity of gene-environment influences and interactions operating on an individual. A top-down systems approach is used to model the effects of lifelong caloric restriction, which is known to extend life span in several animal models. The metabolic phenotypes of caloric-restricted (CR; n = 24) and pair-housed control-fed (CF; n = 24) Labrador Retriever dogs were investigated [to] model both generic and age-specific responses to caloric restriction.
Three aging metabolic phenotypes were resolved: (i) an aging metabolic phenotype independent of diet, characterized by high levels of glutamine, creatinine, methylamine, dimethylamine, trimethylamine N-oxide, and glycerophosphocholine and decreasing levels of glycine, aspartate, creatine and citrate indicative of metabolic changes associated largely with muscle mass; (ii) an aging metabolic phenotype specific to CR dogs that consisted of relatively lower levels of glucose, acetate, choline, and tyrosine and relatively higher serum levels of phosphocholine with increased age in the CR population; (iii) an aging metabolic phenotype specific to CF dogs including lower levels of lipoprotein fatty acyl groups and allantoin and relatively higher levels of formate with increased age in the CF population.
There was no diet metabotype that consistently differentiated the CF and CR dogs irrespective of age. Glucose consistently discriminated between feeding regimes in dogs (≥312 weeks), being relatively lower in the CR group. However, it was observed that creatine and amino acids (valine, leucine, isoleucine, lysine, and phenylalanine) were lower in the CR dogs (earlier than 312 weeks), suggestive of differences in energy source utilization. [Analysis] of longitudinal serum profiles enabled an unbiased evaluation of the metabolic markers modulated by a lifetime of caloric restriction and showed differences in the metabolic phenotype of aging due to caloric restriction, which contributes to longevity studies in caloric-restricted animals.