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 life-long 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 using Orthogonal Projection to Latent Structures-Discriminant Analysis (OPLS-DA) to establish both generic and age-specific responses to caloric restriction from the 1H NMR blood serum profiles of young and older dogs. Three aging metabolic phenotypes were resolved, the first was 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. A second aging metabolic phenotype specific to CR dogs which consisted of relatively lower levels of glucose, acetate, choline and tyrosine and relatively higher levels of phosphocholine associated with beneficial aging outcomes and preservation of neurological function. The third aging metabolic phenotype was specific to CF dogs and included lower levels of liproprotein fatty acyl groups, allantoin and relatively higher levels of formate, which were indicative of metabolic risk factors associated with obesity, diabetes and blood pressure. There was no diet metabotype that consistently differentiated the CF and CR fed dogs irrespective of age. However, it was observed that creatine and amino acids; valine, leucine, isoleucine, lysine, and phenylalanine were lower in the CR fed dogs (<312 weeks), suggestive of differences in energy source utilization. Glucose consistently discriminated feeding regime in dogs (>= 312 weeks), being relatively lower in the CR group. 1H NMR spectroscopic analysis of longitudinal serum profiles enabled an unbiased evaluation of the metabolic markers modulated by life-time of caloric restriction. OPLS-DA provided a framework, such that significant metabolites relating to life extension could be differentiated and integrated with aging processes.