The objectives of this project are to determine the physiological mechanisms and functional significance of age-related changes in circadian rhythms and sleep and to examine the feasibility and efficacy of corrective strategies. Our long-term goal is to enhance the health and life quality of older adults by improving nocturnal sleep, decreasing daytime sleepiness and re-establishing the hormonal correlates of a normal sleep-wake cycle. This multidisciplinary project combines the efforts of investigators at the University of Chicago and at Northwestern University and includes non- invasive studies in subjects in assisted living facilities, Clinical Research Center studies of middle-aged and older adults, in vivo studies of circadian rhythmicity and sleep in hamsters and rats and in vitro molecular studies. Project #1 will determine whether the timings of photic and activity exposure are critical for their beneficial effects and explore the efficacy of strategies increasing the magnitude of non-photic inputs to consolidate sleep and improve daytime function in nursing home residents. Project #2 will test the hypothesis that midlife decreases in both non- photic and photic inputs to the circadian system may contribute to the development of alterations of circadian function, sleep and endocrine function in late life as well as explore strategies designed to restore exposure to non-photic and photic inputs to correct such alterations in midlife and late life. Project #3 will determine the chronology of age- related changes in the circadian system, test hypotheses regarding the role of Neuropeptide Y in causing alterations in non-photic inputs and explore corrective strategies involving increased exposure to both photic and non- photic inputs in hamsters. Project #4 will investigate the effect s of aging on the neural and molecular mechanisms subserving photic entrainment and examine the role of genetic factors in age-related changes in expression of circadian rhythmicity. Project #5 will determine the roles of age-related alterations in circadian rhythmicity and pineal function in causing sleep disturbances in rats. These five Project will be supported by three Cores. Core A (Administrative) will provide the overall logistical and financial coordination and assist in the recruitment of older volunteers. Core B (Methods and Analysis) will supply, operate and maintain the equipment used in the five Projects to monitor circadian rhythms and sleep in humans and rodents and provide methods for reporting and analyzing profiles of behavioral and physiological variables. Core C (Laboratory ) will assay blood and/or saliva levels of hormones for Projects #1, #2 and #3.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
3P01AG011412-05S2
Application #
6155462
Study Section
Special Emphasis Panel (ZAG1 (O1))
Project Start
1994-09-01
Project End
2001-11-30
Budget Start
1999-09-30
Budget End
1999-11-30
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
225410919
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
Jiang, Peng; Turek, Fred W (2018) The endogenous circadian clock programs animals to eat at certain times of the 24-hour day: What if we ignore the clock? Physiol Behav 193:211-217
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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