Role of serum insulin-like growth factor I in mammalian brain aging

Modern societies face new public health challenges associated with an increasingly aging population. Among these, pathological conditions linked to brain aging are paramount. Old age is a risk factor for important neurological impairments such as Alzheimer's disease or stroke. Even healthy elderly people usually present with milder forms of cognitive decline. This is possibly related to less-pronounced brain deficits seen in normal aging, including the shrinkage of neurons and the dense network of neurons and glia in the central nervous system known as the neuropil, a lower neurogenetic rate, impaired angiogenesis or brain accumulation of deleterious compounds. At least in mammals, age is also associated with a decline in insulin-like growth factor-I (IGF-I) levels, a well-known neuroprotective agent. Recently, a relationship between serum IGF-I and "house-keeping" mechanisms in the brain has been evidenced in laboratory rodents. Serum IGF-I increases adult neurogenesis, sustains neuronal health through a variety of fundamental homeostatic mechanisms, participates in brain angiogenesis, contributes to brain beta-amyloid clearance and affects learning and memory. Overall, diminished trophic input resulting from decreasing serum IGF-I levels during aging likely contributes to brain senescence in mammals.