The molecular basis for the development of sarcopenia in the elderly
12 / 2007 - onbekend
Aging is associated with a progressive loss of skeletal muscle mass (sarcopenia), leading to an increased risk of developing chronic metabolic diseases. As there are no differences in basal protein turnover (protein synthesis and breakdown) between young and elderly humans, it has been suggested that the elderly are less responsive to the anabolic stimuli like food intake and/or exercise. The muscle protein anabolic response to food intake comprises a protein synthetic and proteolytic component, both tightly regulated by myocellular signaling pathways. It has been shown that the PI-3 kinase/mTOR-signaling pathway plays a major role in regulating muscle protein synthesis, while muscle protein breakdown is, at least partly, regulated by FOXO-mediated signals. Interestingly, FOXO activity can be altered by Akt, a key-protein in the PI3/mTOR pathway. The latter suggests that impairments in the activation of these pathways might modulate the protein synthetic and/or proteolytic response to food intake and/or exercise and, as such, might be instrumental in the etiology of sarcopenia. The aim of this proposal is to study defects in the myocellular regulation of protein synthesis and breakdown in elderly humans. This proposal will provide important information on the molecular basis of the changes in muscle protein metabolism with aging.