Previous studies have provided compelling evidence that the Growth Hormone (GH)–IGF-1 axis is a conserved pathway important for determination of both healthspan and lifespan in diverse organisms. Nevertheless, controversies related to the effects of these hormones remain and will continue until appropriate and translationally relevant animal models that can be developed and used to regulate GH and IGF-1 levels throughout the lifespan. We and our colleagues in several scientific consensus reports have recognized the necessity of new animal models for advancement of the field. The ongoing studies in our laboratory use novel animal models and interventions that are designed to produce one of the most comprehensive and rigorous analyses of the effects of age-related changes in IGF-1 on pathology and lifespan using a pre-clinical, translationally relevant approach.