Aging and peptide control of food intake.

Aging affects energy homeostasis and fuel metabolism in a form of either an increased body mass and glucose intolerance that may lead to obesity and type 2 diabetes or loss of appetite that also may seriously compromise health status. The data, obtained mainly in rat, suggest that aging suppresses the expression and action of potent orexigenic peptides such as predominantly neuropeptides NPY and orexins as peripheral hormone, ghrelin. Senescent animals show over-responsiveness to αMSH, the major anorexigenic neuropeptide. However, central anorexigenic action of leptin is clearly diminished in aging, most likely due to the impaired leptin signal transduction. The age-related central resistance to leptin and insulin does not reduce their inhibitory effects on the activity of NPY and AgRP neurons. Thus, in rodents aging is associated with the altered expression and activity of both orexigenic and anorexigenic peptides. If similar changes in the central regulation of food intake occur during human aging, they may partially explain 'anorexia of aging' and loss of body weight observed at the end-of-life period. Additionally, increased plasma cholecystokinin concentrations in healthy old subjects may also contribute to the loss of appetite characteristic for the elderly. Further studies of the central and peripheral mechanisms that control food intake during aging may provide novel therapeutic strategies to improve the nutritional status of the elderly.