Effects of age and training on the cytokine, myokine, and endocrine regulation of glucose metabolism in standardbred mares

Age adversely affects the hypothalamic-pituitary-adrenal axis (HPAA) and glucose metabolism in horses. Changes may be attenuated with exercise training, but mechanisms behind these phenomena are unknown. Six old (22.0 +/- 0.7 yrs; mean +/- SE) and six young (7.3 +/- 0.6 yrs) healthy, unfit Standardbred mares were utilized to test several hypotheses: 1) the HPAA response, plasma insulin and glucose concentrations differ in old and young mares during acute, exhaustive exercise vs. recovery, and differences are altered after exercise training; 2) aging and training alter cortisol, ACTH and glucose responses to endocrine stimulation tests; 3) old and young mares have different endocrine responses to a frequently sampled intravenous glucose tolerance test along with different cytokine profiles in blood, adipose and muscle tissues; and 4) exercise training would alter endocrine and cytokine profiles. A separate pilot study tested the hypothesis that equine blood, muscle and adipose tissue harbor different quantities of cytokine mRNA, and young horses (≤10 yrs) have different cytokine profiles in these tissues and blood compared to old (≤20 yrs) horses. Mares ran three graded exercise tests, one pre-training, one after 8 weeks of training at 60% maximum heart rate, and the third at the conclusion of the study at 15 weeks. Training appears to condition the HPAA to a lesser response to acute, exhaustive exercise in both age groups. Old and young mares improved insulin sensitivity and pancreatic beta cell function after training, and there were significant differences in tissue cytokine profiles. In the pilot study, novel data demonstrated varied cytokine profiles in blood, adipose (abdominal and subcutaneous) and muscle tissues in horses of mixed breeds and backgrounds, but no age differences were noted. In summary, altered hormone and glucose concentrations in aged animals may adversely affect the ability to maintain and recover from strenuous exercise. Training was successful in partially reversing these changes. Exact mechanisms for the changes remain to be elucidated, but evidence presented here demonstrates that changes occur at multiple levels of the HPAA and involve factors including hormones, glucose and inflammatory cytokines.