Chronic partial sleep restriction (CPSR) is a hallmark of life in modern human society however, only recently have the consequences of CPSR for chronic human illnesses such as obesity and diabetes come to be fully appreciated. Despite the growing awareness of the importance of sleep as a factor in human health and in the development of age-related diseases, few animal models have been developed to systematically determine how aging effects the consequences of CPSR on the sleep-wake regulatory system itself and on other physiological processes, such as energy metabolism and circadian rhythms. During the previous funding period, we developed a model of CPSR that led to the exciting discovery that after only a few days of CPSR, both young and old rats no longer exhibited a homeostatically regulated sleep recovery pattern;they failed to generate increases in NREM EEG delta power and NREM sleep time. In addition, we demonstrated an impact of CPSR on leptin and glucocorticoid concentrations, glucose tolerance, and insulin responsiveness in young rats. These data led us postulate a novel hypothesis that repeated episodes of sleep restriction result in the transition from a homeostatic to an allostatic state of sleep regulation that may lead to adaptive changes in the sleep-wake and other physiological systems to cope with the immediate environmental challenge inducing sleep loss. However, such initially adative changes could have adverse effects if the allostatic response to CPSR is maintained for a prolonged period of time. In the proposed studies, we will systematically examine this working model in two Specific Aims (1) Test the hypothesis that aging accelerates the transition from homeostatis to allostasis during CPSR. Specifically, we will determine if aging impacts the severity and duration of sleep restriction necessary to cause the transition from a homeostatic to an allostatic sleep regulatory state (2) Test the hypothesis that aging alters the effects of CPSR on key hormonal and molecular components of energy metabolism and circadian clock gene expression in the CMS and peripheral tissues, and that the adverse effects of CPSR on metabolism are a consequence and are exacerbated by the transition from a homeostatic to an allostatic sleep regulatory state

Public Health Relevance

The use of an animal model to determine the effects of chronic partial sleep restriction (CPSR) and how aging impacts the response to CPSR, is expected to lead to new insights into the biological mechanisms that link short sleep in humans with cardiometabolic diseases, and new therapeutic strategies for treating age- related metabolic and associated disorders, such as obesity, diabetes, and cardiovascular disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG011412-17
Application #
8448189
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
17
Fiscal Year
2013
Total Cost
$219,764
Indirect Cost
Name
University of Chicago
Department
Type
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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