Our group has identified reduced sleep duration as a novel risk factor for obesity and type 2 diabetes. During the previous grant period, we have shown that reduced sleep quality, specifically reduced deep slow-wave sleep (SWS), has adverse cardiometabolic consequences and obtained evidence that a """"""""vicious cycle"""""""" may interconnect sleep and circadian disruption with cardiometabolic disease. In both humans and rodents, we further observed that chronic partial sleep restriction alters the homeostatic regulation of sleep, a phenomenon that may be referred to as an """"""""allostasis"""""""" of sleep regulation. Normal aging is associated with reductions in sleep duration, sleep quality and circadian function. The present Program Project focuses on the interactions between chronic reductions of sleep duration, sleep quality and circadian function and the age-related increase in cardiometabolic disease. A multi-disciplinary approach combining statistical analyses of a large data set, clinical research (in healthy adults of all ages, older insomniacs, and older adults with sleep disturbances), in vivo studies in a rodent model of chronic partial sleep loss and molecular and genetic analyses will be used to: 1. test the hypothesis that individuals with low SWS because of age, ethnicity or genetic factors, are at higher risk for type 2 diabetes (human studies, E. Van Cauter, PI);2. test the hypothesis that the preservation or restoration of SWS has beneficial cardiometabolic effects (human studies, E. Tasali, PI);3. test the hypothesis that the most common types of insomnia in older adults are associated with reduced SWS and cardiometabolic alterations (human studies;P.C. Zee, PI);4. perform a comprehensive evaluation of the impact of age on sleep allostasis during chronic partial sleep restriction and determine the cardiometabolic consequences (rat studies;F.W. Turek, PI);5. dissect the molecular basis for accelerated metabolic aging induced by circadian disruption and sleep loss (mouse studies;J. Bass, PI). Core A (Administrative) will provide logistic and financial coordination. Core B (Methods and Analysis) will standard operating procedures for data collection, archival and analysis. Core C will assay peripheral levels of hormones, cytokines and other blood constituents.

Public Health Relevance

The proposed studies are expected to elucidate the role of sleep and circadian disturbances in metabolic aging. The findings will provide the basis for interventions to delay the development or decrease the severity of age-related cardiometabolic disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
3P01AG011412-17S1
Application #
8848561
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5 (J1))
Program Officer
Mackiewicz, Miroslaw
Project Start
1997-02-01
Project End
2015-03-31
Budget Start
2014-06-01
Budget End
2015-03-31
Support Year
17
Fiscal Year
2014
Total Cost
$64,545
Indirect Cost
$8,700
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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Peek, Clara Bien; Levine, Daniel C; Cedernaes, Jonathan et al. (2017) Circadian Clock Interaction with HIF1? Mediates Oxygenic Metabolism and Anaerobic Glycolysis in Skeletal Muscle. Cell Metab 25:86-92
Mokhlesi, Babak; Grimaldi, Daniela; Beccuti, Guglielmo et al. (2017) Effect of one week of CPAP treatment of obstructive sleep apnoea on 24-hour profiles of glucose, insulin and counter-regulatory hormones in type 2 diabetes. Diabetes Obes Metab 19:452-456
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Fan, Emily P; Abbott, Sabra M; Reid, Kathryn J et al. (2017) Abnormal environmental light exposure in the intensive care environment. J Crit Care 40:11-14
Santostasi, Giovanni; Malkani, Roneil; Riedner, Brady et al. (2016) Phase-locked loop for precisely timed acoustic stimulation during sleep. J Neurosci Methods 259:101-114
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
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
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; Kilkus, Jennifer M; Delebecque, Fanny et al. (2016) Elevated ghrelin predicts food intake during experimental sleep restriction. Obesity (Silver Spring) 24:132-8

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