The Insulin-like Growth Factor System and Aging.

Abstract

There is strong evidence that insulin-like growth factor (IGF) signaling is involved in fundamental aspects of the aging process. However, the extracellular part of the IGF system is complex with various receptors, ligand effectors, high affinity IGF binding proteins, proteinases and endogenous inhibitors that all, along with their biological context, must be considered. The IGF system components are evolutionarily conserved, underscoring the importance of understanding this system in physiology and pathophysiology. This review will briefly describe the different components of the IGF system and then discuss past and current literature regarding the IGFs and aging, with a focus on cellular senescence, model organisms of aging, centenarian genetics, and three age-related diseases - pulmonary fibrosis, Alzheimer's disease, and macular degeneration - in appropriate murine models and in humans. Commonalities in mechanism suggest conditions where IGF system components may be disease drivers and potential targets in promoting healthy aging in humans.