Age correlated reductions in the density of many physiologic receptors have been demonstrated, along with age correlated reductions in receptor function. It is now accepted that the capacity of many physiologic systems decline with age. But the reason this occurs is unknown. If the mechanism by which this age related reduction in physiologic capacity were known, methods to prevent it could possibly be developed, and some diseases related to the aged state, potentially more effectively treated. It is not known whether the age related reductions in receptor populations are due solely to decreases in protein synthetic ability, or not. Indeed, it is not known whether the age related decrease in protein synthetic ability arises de novo, or is triggered by a cellular event. Some receptor systems are desensitized acutely by endogenous agents. Guanyl nucleotides, for instance, cause acute reductions in the density of some receptors. The specific hypothesis of this proposal is that the ability of receptors to undergo acute desensitization is also lost with age, and further, that this ability is lost prior to the loss of receptors. If the results support this hypothesis, it will suggest that the ability of a cell to regulate receptor density acutely is intimately associated with the maintenance of the protein synthetic mechanisms involved in the control of cell receptor density throughout the life span.
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