THE ROLE OF GHRELIN DURING AGING

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DESCRIPTION: (Adapted from the applicant's abstract) This application addresses a number of questions regarding the activity both endogenous (Ghrelin) and synthetic (GH releasing peptide, GHRPs, such as MK-0677) ligands for the Growth Hormone Secretagogue Receptor (GHS-R) and the nature of their interaction. The application has an overall aim of elucidating the physiologic role of GHS-R, especially as it relates to aging. It is predicated on a significant amount of preliminary data, and driven by a number of hypotheses. Specifically, four aims are proposed: 1) determine the function of the octanoyl moiety on Ghrelin and its role in Ghrelin's interaction with the GHS-R, 2) using site directed mutagenesis, determine the characteristics of the GHS-R binding pocket(s) that interact with Ghrelin, a putative truncated Ghrelin 1-14, and synthetic GHRPs, 3) Determine whether Ghrelin and its potential alternate forms stimulate activity in hypothalamic neuron and define the hypothalamic neurons that respond to these ligands and, 4) determine whether aging is associated with a decline in Ghrelin activity; then whether such a putative decline is due to a decrease in Ghrelin acylating activity.