SLEEP DISORDERED BREATHING IN AGING ZUCKER RATS

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Changes in sleep and sleep quality in late life have implications for quality of life, level of functioning, and ability to remain independent. Complaints in initiating and maintaining sleep and of daytime drowsiness are among the most common health problems in the elderly. Sleep disordered breathing (SDB) is prevalent in the elderly and associated with severe and often life-threatening complications. Although the clinical features of SDB have been well described, the sequence of events and mechanisms responsible for initial increases in airway resistance or subsequent age associated devolution of the upper airway toward full occlusion (obstructive sleep apnea, OSA) remain unknown. Although it has been speculated that mild forms of SDB (upper airway resistance syndrome with snoring) and OSA represent the two extremes of a continuum of the same disorder, central and peripheral mechanisms that contribute to or enhance movement along this continuum are not fully understood. Because of the slow progression of SDB in humans, and the fact that most clinical studies have had to revert to a cross-sectional design, contributing factors associated with SDB in an aging population have proved difficult to delineate. Unquestionably, a suitable animal model that shares many of the same characteristics as noted in human SDB would be of tremendous value in determining consequential mechanisms responsible for the evolution of SDB in the aging population. The Zucker (Z.) Rat, an autosomal genetic model of obesity, offers many advantages as a model for studying the evolution of SDB: obese animals are not born obese, but develop the increased body mass as a function of age; a relatively short life-span (18 months) is ideal for inclusion of longitudinal studies to correlate specific mechanisms with age related dysfunction; the Z. Rat is very well defined as attested by the vast number of studies employing this model since its original description in 1961; the size is ideal to perform numerous perturbations and to study influences originating from secondary factors; obese Z. Rats present many of the same functional, central, and sleep state abnormalities as observed in humans with SDB; and lean litter-mates are available to serve as age- matched controls. The major hypothesis to be tested is that SDB naturally evolves in aging obese Z. rats and such this model will prove most advantageous in detecting mechanisms associated with the evolution of SDB. Only after these contributing mechanisms are fully understood can effective early interventions be contemplated.