Aging of the brain, neurotrophin signaling, and Alzheimer's disease: is IGF1-R the common culprit?
The last decade has revealed that the lifespan of an organism can be modulated by the signaling pathway that acts downstream of the insulin/insulin-like growth factor 1 receptors (IR/IGF1-R), indicating that there is a "program" that drives the process of aging. New results have now linked the same pathway to the neurogenic capacities of the aging brain, to neurotrophin signaling, and to the molecular pathogenesis of Alzheimer's disease. Therefore, a common signaling cascade now seems to link aging to age-associated pathologies of the brain, suggesting that pharmacologic approaches aimed at the modulation of this pathway can serve to delay the onset of age-associated disorders and improve the quality of life. Work from a wide range of fields performed with different approaches has already identified some of the signaling molecules that act downstream of IGF1-R, and has revealed that a delicate checkpoint exists to balance excessive growth/"immortality" and reduced growth/"senescence" of a cell. Future research will determine how far the connection goes and how much of it we can influence.
Puglielli
Luigi
L
Department of Medicine, University of Wisconsin-Madison, and Geriatric Research Education Clinical Center, VA Medical Center, VAH-GRECC 11G, 2500 Overlook Terrace, Madison, WI 53705, USA. lp1@medicine.wisc.edu
D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008959:Models, Neurological; D009414:Nerve Growth Factors / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction
D016229:Amyloid beta-Peptides; D009414:Nerve Growth Factors; D017526:Receptor, IGF Type 1