The Role of the IGF-1 and its Partners in Central and Peripheral Metabolism: Considerations for Extending Healthy Life Span

Abstract

There is growing evidence to suggest a role for GH/IGF system in regulation of life span, or rate of aging. The role of IGF-1 in aging and disease is very complex. High IGF-1 levels is associated with cancers and low IGF-1 has been implicated in the pathogenesis of a wide range of conditions including diabetes and glucose intolerance, osteoporosis, poor cognitive function and coronary heart disease, thus highlighting the complex role of IGF axis in humans. In addition, we have shown that members of GH/IGF axis, IGF-1, IGFBP-3 as well as a novel binding partner for IGFBP-3 termed HN influence glucose metabolism through the hypothalamus. This suggests that acute regulation of peripheral insulin action is probably elicited in the hypothalamus and the integrity of GH/IGF system is probably needed to ensure normal metabolism with aging. Therefore, it is intriguing to speculate that an ability to ameliorate the age-associated decline in CSF IGF-1 levels without increasing circulating IGF-1 levels would be beneficial in potentially preventing or treating two scourges with enormous morbidity and mortality, diabetes and cancer. Potentially, administration of IGF-1 receptor antagonists that does not cross the blood brain barrier, will protect peripheral tissues from cancer, yet will allow IGF-1 to act in the brain to allow the beneficial effects related to other diseases such as cognition and glucose tolerance. In addition, the newest link to IGF system, HN could offer exciting patho-physiologic links as well as potential treatment options for neuro-degeneration and diabetes.