The data available on GHR−/− at all ages. Glucose levels, which are very low in young animals, seem to normalize at older ages. Insulin levels remain significantly lower than normal throughout the lifespan of GHR−/− mice. Together, these data suggest that insulin sensitivity decreases only slightly as GHR−/− mice age. In addition, circulating lipid levels tend to be decreased, adding to the scenario of improved metabolic health in GHR−/− mice. However, the need for closer inspection of the age-dependent changes in metabolism in these mice is apparent. Given the age-dependent variation observed in blood glucose levels, it becomes critical to establish the insulin responsiveness of target organs in GHR−/− mice of different ages. Interestingly, data available on liver suggest an insulin-resistant state in older animals. This seems counterintuitive given that whole-body insulin sensitivity is enhanced in GHR−/− mice even at old age. Therefore, it would be interesting to evaluate the insulin responsiveness of the liver in young GHR−/− animals to determine the role of this organ in whole-body insulin sensitivity. Similarly, a thorough characterization of the age-specific degree of insulin sensitivity in skeletal muscle and heart is needed to complement the data that are already available. Furthermore, focus needs to be applied on adipose tissue, given that it is one of the main target organs of insulin and GH action and a key player in metabolic regulation (see Chap. 51).