Objective: The somatotropic axis is crucial for development, from conception to adulthood. Growth hormone (GH) primarily acts on the liver to induce insulin-like growth factor I (IGF-I) secretion but also directly affects other tissues, impacting adult physiology. Once secreted, IGF-I binds its receptor (IGF-1R) to promote growth. Both GH and IGF-I are essential for health throughout life, beneficial in young patients with growth delay, and thought to aid tissue rejuvenation during aging. The physiological decline of GH and IGF-I with age is proposed as a factor in aging. To clarify the roles of GH and IGF-I in tissue homeostasis, we developed a mouse with a complete IGF-1R knockout induced in all adult tissues. This mutant is viable, lean, shows resilient energy metabolism, and presents with normal cognition. Lifelong observation suggested that stem cell behavior is affected in this mouse model. Methods: Stem cell proliferation in intestinal and skin epithelia during aging was studied using multiple labeled thymidine analogues administered via the drinking water. Body composition was monitored throughout life. Results: The IGF-1R knockout mice exhibited increased circulating GH and IGF-I due to the loss of all neuroendocrine negative feedback. Over time, mutants showed progressive decline of body weight into old age, indicating that the disruption of the somatotropic axis profoundly altered tissue homeostasis, affecting lean and fat tissues. Epithelial stem cell proliferation increased shortly after IGF-1R knockout induction but decreased as mutants age. Conclusion: Our findings suggest that GH hypersecretion resulting from disrupted IGF-1R signaling strongly influences the body composition and the long-term maintenance of tissues, possibly through altering stem cell homeostasis. The decline in somatotropic hormones normally observed with aging may act as a protective mechanism against tissue damage during aging.