Chronic sleep disturbance is reported by nearly 50% of older adults. Sleep loss also occurs at all ages due to bedtime curtailment, an increasingly prevalent condition. Recent data have revealed the role of sleep duration and quality in metabolic and endocrine function and have indicated that chronic sleep loss may accelerate the development or increase the severity of age-related diseases such as obesity and diabetes. Despite its high prevalence, chronic sleep loss has been understudied. The present Project focuses on the interaction of chronic partial sleep loss and aging. A multi-disciplinary approach combining epidemiology, clinical research (in older insomniacs, middle-aged subjects at risk for obesity and healthy adults of all ages), in vivo studies in laboratory rodents and molecular and genetic analyses will be used to: 1. Delineate the impact of age on sleep regulation during adaptation to and recovery from chronic partial sleep loss; 2. Test the hypothesis that chronic partial sleep loss has adverse effects on biomarkers of aging and increases the risk of obesity and diabetes; 3. Test the hypothesis that paying a sleep debt and/or improving sleep quality has beneficial health and neurobehavioral effects at all stages of adulthood; 4. Determine the influence of the circadian clock on the response to chronic sleep loss; 5. Explore the mechanisms linking chronic sleep loss and metabolic aging; 6. Define the determinants of individual differences in sleep capacity and vulnerability to sleep loss in young adulthood, midlife and late life. Project 6 will determine the role of sleep in weight gain in mid life. Project 7 will examine whether exercise is an effective countermeasure for sleep loss in older insomniacs. Project 8 will delineate the role of sleep duration in metabolic aging and weight gain. Project 9 will determine the impact of a sleep debt and individual sleep capacity in young, middle-aged and older men and women. Project 10 will use rat models to define the impact of age on physiologic adaptation to and recovery from sleep restriction. Project 11 will utilize a genetic model of chronic sleep loss with age-related obesity, the Clock mouse, to explore mechanisms linking circadian function, sleep and metabolism. Core 9001 (Methods and Analysis) will provide monitoring equipment for humans and rodents, methods for quantifying output variables and biostatistical support. Core 9002 (Laboratory) will assay blood, saliva and urine constituents for Projects 7, 8 & 9.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
2P01AG011412-08
Application #
6571513
Study Section
Special Emphasis Panel (ZAG1-ZIJ-3 (O3))
Program Officer
Monjan, Andrew A
Project Start
1994-09-01
Project End
2008-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
8
Fiscal Year
2003
Total Cost
$2,179,521
Indirect Cost
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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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Hong, Hee-Kyung; Maury, Eleonore; Ramsey, Kathryn Moynihan et al. (2018) Requirement for NF-?B in maintenance of molecular and behavioral circadian rhythms in mice. Genes Dev 32:1367-1379
Guyon, Aurore; Morselli, Lisa L; Balbo, Marcella L et al. (2017) Effects of Insufficient Sleep on Pituitary-Adrenocortical Response to CRH Stimulation in Healthy Men. Sleep 40:
Baron, Kelly Glazer; Reid, Kathryn J; Malkani, Roneil G et al. (2017) Sleep Variability Among Older Adults With Insomnia: Associations With Sleep Quality and Cardiometabolic Disease Risk. Behav Sleep Med 15:144-157
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
Jiang, Peng; Turek, Fred W (2017) Timing of meals: when is as critical as what and how much. Am J Physiol Endocrinol Metab 312:E369-E380

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