Aged-related changes in the discrete brain structure responsible for the generation and organization of circadian rhythmicity in mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus, may play a role in the pathophysiology of aged-related disruptions in the timing and organization of sleep and wakefulness. Assessment of age-related changes in circadian function and their relationship to the timing and regulation of sleep, neuroendocrine and thermoregulatory cycles requires investigation at a number of levels: clinical, behavioral, neurophysiologic, cellular and molecular. The multidisciplinary approach adopted for study of the organization and function of the circadian timing system in this program project incorporates four studies-two conducted in humans (one sighted population; on blind population) and two in animals (one involving neural tissue transportation; the other gene expression). The common goal of this program project, which lies at the interface of neurophysiology and behavior, is to identify changes in the central circadian pacemaker that are associated with aging; to demonstrate that the age of a discrete brain structure, the SCN, is the critical determinant of those changes; and furthermore to relate the neurophysiology to observe behaviors. To achieve this goal, the program project will draw on the expertise of the following discipline; circadian physiology, endocrinology, genetics, neurophysiology, electroencephalography, polysomnography, ophthalmology, gerentology, neurology, molecular biology, cell physiology, psychology, protein chemistry, tissue transportation, temperature regulation, oscillator theory, and statistics. Each of the four proposals is designed to provide for integration among projects. In particular, all projects will specifically assess the phase, amplitude and/or intrinsic period of measurable rhythmic outputs generated by the endogenous circadian pacemaker. A common language of data, facilitating interspecies comparisons and synergistic interaction. Further understanding of the neurophysiological changes associated with aging may provide insight into the pathophysiological of age-related sleep disorders. In addition, much may be learned about the mechanism involved in aging of central nervous tissue, and how they affect physiology and behavior. The structure of this project will facilitate the exchange and integration of molecular, physiologic and behavioral data from studies of the circadian timing system focusing on changes related to advancing age.
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