| Abstract: | Aging is associated with decreased levels of growth hormone and both circulating and local levels of insulin-like growth factor-I (IGF-I). The decline in IGF-I has been postulated to be important in both physiological aging and pathological states that are seen with aging. In parallel, inappropriate apoptosis is thought to play a role in some of these same processes. In experimental models, IGF-I signalling through the IGF-I receptor confers a protective effect from apoptosis. This review summarizes the results of studies documenting the IGF-I anti-apoptotic effect in neuronal model systems. The known downstream signalling cascades that mediate this signal are beginning to be elucidated; these include MAP kinase and Akt. In addition, IGF-I prevents the reduction of anti-apoptotic proteins of the bcl-2 family induced by hyperosmotic conditions in cultured neuronal cells. IGF-I has been shown to positively impact on tau, the microtubule-associated protein, possibly preventing the degradation of proteins that are associated with the neurofibrils seen in Alzheimer's disease. All of the studies to date support the hypothesis that appropriately high levels of IGF-I signalling prevent some of the processes associated with aging. |
