PROJECT SUMMARY Homeostasis is a feature of all bodily structures and represents the maintenance of stability within these structures to facilitate optimal functioning. During aging or with the development of diseases, homeostenosis or a narrowing of the functional reserves necessary to preserve homeostasis, occurs. The loss of functional reserve in one system leads to the body depleting other reserve systems to maintain function. Eventually, the continual use and depletion of multiple reserve systems leads to frailty which greatly affects the ability of the body to function and makes individuals more susceptible to negative health outcomes. Eating and drinking represent body functions vital to achieving nutritional homeostasis which is necessary for survival. Dysphagia, or swallowing impairment, is a threat to maintaining nutritional homeostasis as deficits in swallowing safety (airway invasion) and efficiency (residue) can lead to malnutrition and dehydration. The loss of functional reserves has been implicated to contribute to the development of dysphagia in diseases and in the elderly, however, the dysregulation of homeostatic mechanisms and its? effect on optimal swallowing function is not understood. The overarching goal of this fellowship proposal is to investigate mechanisms of homeostatic dysfunction as it relates to the development of swallowing impairments. In the F99 phase of this proposed research, I will evaluate the impact of functional reserve depletion in one structure important for swallowing (the tongue) on swallowing function in individuals with ALS. Specifically, I will develop a novel lingual pressure protocol to determine patterns of lingual functional reserve decline in ALS and examine potential relationships between lingual pressure patterns and lingual reserve depletion with functional aspects of swallowing safety and efficiency. I will also evaluate whether a critical threshold of homeostenotic lingual functional reserve depletion exists wherein lingual and swallowing impairments ensue. During the K00 phase, I will move to a complementary laboratory to investigate swallowing function in the frail elderly with multiple, diminished functional reserves and evaluate the physiological differences in swallowing function that occur in the frail elderly versus normal aging. The long term goal of the proposed work is to generate the knowledge necessary for the future development of biologically informed therapeutics to target swallowing dysfunction across various patient populations. The completion of this work will provide important insight into dyregulation of homeostatic mechanisms and functional reserve in vulnerable populations (ALS and the elderly) and will yield a novel lingual pressure testing protocol (F99 phase) and characterization of frail swallowing in the elderly (K00 phase) that will further our understanding of the role of homeostenosis on the vital functions of eating and drinking.