Editorial Volume 15, Issue 3 pp 599—600

Figure 1. Aging is associated to widespread IGF-IR resistance, including the brain. As IGF-IR may act as a dependence receptor, age-related loss of regulation by IGF-I will unveil ligand-independent actions, such as pro-aging, pro-apoptosis or blockade of glucose uptake, that in turn may contribute to age-associated brain diseases. The latter may be due to unrestrained activity of the receptor since IGF-IR resistance is frequent in many age-related diseases of the brain. Conversely, age-associated brain diseases may lead to further IGF-IR resistance in a vicious cycle, as disease-associated processes such as oxidative/endoplasmic reticulum stress or inflammation elicit IGF-IR resistance. Thus, inhibition of IGF-I-resistant IGF-IR, or its sensitization to re-gain control by IGF-I, will restrain its downstream detrimental actions.