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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1-ZIJ-5 (J1))
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Mackiewicz, Miroslaw
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University of Chicago
Internal Medicine/Medicine
Schools of Medicine
United States
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Morselli, Lisa L; Gamazon, Eric R; Tasali, Esra et al. (2018) Shared Genetic Control of Brain Activity During Sleep and Insulin Secretion: A Laboratory-Based Family Study. Diabetes 67:155-164
Temple, Karla A; Leproult, Rachel; Morselli, Lisa et al. (2018) Sex Differences in the Impact of Obstructive Sleep Apnea on Glucose Metabolism. Front Endocrinol (Lausanne) 9:376
Morselli, Lisa L; Temple, Karla A; Leproult, Rachel et al. (2018) Determinants of Slow-Wave Activity in Overweight and Obese Adults: Roles of Sex, Obstructive Sleep Apnea and Testosterone Levels. Front Endocrinol (Lausanne) 9:377
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