In the golden hamster, there are pronounced age-related changes in the expression of circadian rhythm under both entrained and free-running conditions, as well as in the response of the circadian clock system to a variety of photic and non-photic stimuli. Studies performed during the previous grant period have provided important observations in three areas pertaining to the development of such age-related alterations, their underlying mechanisms and possible approaches for corrective strategies. The proposed studies will build on these findings to 1) determine the chronology of the development of various age-related changes in the circadian clock system, 2) to determine the physiological mechanisms underlying age-related changes in the circadian clock system and 3) to test the efficacy of specific countermeasures to reverse or attenuate the effects of aging on circadian rhythmicity. In particular, various hypotheses will be tested regarding the role of serotonin and neuropeptide Y, as well as the influence of the pineal gland and its hormone melatonin, in age-related changes in the circadian system. Countermeasures involving treatment with melatonin or altering the strength of the entraining light- dark cycle will be employed to test the hypothesis that age-related changes in the circadian system can be attenuated, delayed or reversed. Throughout the proposed studies, the effects of aging on the expression of five different rhythms (i.e., wheel-running behavior, total locomotor activity, drinking behavior, body temperature and circulating melatonin levels), and on the ability of the circadian pacemaker to be phase shifted by either photic or non-photic stimuli, will be determined in hamsters. It is anticipated that the elucidation of the physiological basis for age- related changes in circadian function, and of the mechanisms which underlie the efficacy of various corrective strategies, will lead to new insights into the regulation and organization of circadian rhythmicity and of its interaction with environmental stimuli. These studies are also expected to lead to new clinical approaches for treating, preventing or delaying disturbances of circadian rhythms and sleep in older human populations.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
3P01AG011412-05S1
Application #
6098501
Study Section
Project Start
1999-04-01
Project End
1999-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
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
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
Bass, Joseph T (2017) The circadian clock system's influence in health and disease. Genome Med 9:94
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
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:

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