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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Chicago
United States
Zip Code
Santostasi, Giovanni; Malkani, Roneil; Riedner, Brady et al. (2016) Phase-locked loop for precisely timed acoustic stimulation during sleep. J Neurosci Methods 259:101-14
Peek, Clara Bien; Levine, Daniel C; Cedernaes, Jonathan et al. (2016) Circadian Clock Interaction with HIF1α Mediates Oxygenic Metabolism and Anaerobic Glycolysis in Skeletal Muscle. Cell Metab :
Broussard, Josiane L; Kilkus, Jennifer M; Delebecque, Fanny et al. (2016) Elevated ghrelin predicts food intake during experimental sleep restriction. Obesity (Silver Spring) 24:132-8
Grimaldi, Daniela; Carter, Jason R; Van Cauter, Eve et al. (2016) Adverse Impact of Sleep Restriction and Circadian Misalignment on Autonomic Function in Healthy Young Adults. Hypertension 68:243-50
Broussard, Josiane L; Wroblewski, Kristen; Kilkus, Jennifer M et al. (2016) Two Nights of Recovery Sleep Reverses the Effects of Short-term Sleep Restriction on Diabetes Risk. Diabetes Care 39:e40-1
Mokhlesi, Babak; Grimaldi, Daniela; Beccuti, Guglielmo et al. (2016) Effect of One Week of 8-Hour Nightly Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea on Glycemic Control in Type 2 Diabetes: A Proof-of-Concept Study. Am J Respir Crit Care Med 194:516-9
Broussard, Josiane L; Van Cauter, Eve (2016) Disturbances of sleep and circadian rhythms: novel risk factors for obesity. Curr Opin Endocrinol Diabetes Obes 23:353-9
Perelis, M; Ramsey, K M; Bass, J (2015) The molecular clock as a metabolic rheostat. Diabetes Obes Metab 17 Suppl 1:99-105
Perelis, Mark; Marcheva, Biliana; Ramsey, Kathryn Moynihan et al. (2015) Pancreatic β cell enhancers regulate rhythmic transcription of genes controlling insulin secretion. Science 350:aac4250
Westerberg, Carmen E; Florczak, Susan M; Weintraub, Sandra et al. (2015) Memory improvement via slow-oscillatory stimulation during sleep in older adults. Neurobiol Aging 36:2577-86

Showing the most recent 10 out of 194 publications