Abstract
Insulin-like growth factor-1 (IGF-1) is an important anabolic hormone that decreases with age. In the past two decades, extensive research has determined that the reduction in IGF-1 is an important component of the age-related decline in cognitive function in multiple species including humans. Deficiency in circulating IGF-1 results in impairment in processing speed and deficiencies in both spatial and working memory. Replacement of IGF-1 or factors that increase IGF-1 to old animals and humans reverses many of these cognitive deficits. Despite the overwhelming evidence for IGF-1 as an important neurotrophic agent, the specific mechanisms through which IGF-1 acts have remained elusive. Recent evidence indicates that IGF-1 is both produced by and has important actions on the cerebrovasculature as well as neurons and glia. Nevertheless, the specific regulation and actions of brain- and vascular-derived IGF-1 is poorly understood. The diverse effects of IGF-1 discovered thus far reveal a complex endocrine and paracrine system essential for integrating many of the functions necessary for brain health. Identification of the mechanisms of IGF-1 actions will undoubtedly provide critical insight into regulation of brain function in general and the causes of cognitive decline with age.
Highlights
Cognitive decline is a common complication of aging that includes alterations in a variety of brain functions including, but not limited to, reductions in processing speed, inductive reasoning, and spatial learning and memory (Hedden and Gabrieli, 2004)
In a model of amyotrophic lateral sclerosis (ALS), Insulin-like growth factor-1 (IGF-1) treatment, acting through astrocytes, reduced neurotoxicity and rescued the disease-associated neurite retraction (Dodge et al, 2008). These results provide some of the first evidence that the age-induced loss of IGF-1 may dramatically influence astrocyte physiology
IGF-1 has profound actions on the cerebrovasculature, glia and neurons yet we are just beginning to understand the complex effects of this hormone and the role of IGF-1 in managing the important interactions that occur between these cell types
Summary
Cognitive decline is a common complication of aging that includes alterations in a variety of brain functions including, but not limited to, reductions in processing speed, inductive reasoning, and spatial learning and memory (Hedden and Gabrieli, 2004). Impairment of these functions is closely associated with a decrease in both health-span and independence. Within these regions impaired synaptic signaling is especially affected by aging (reviewed in Hof and Morrison, 2004) and is likely the final common pathway to cognitive impairment
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