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.
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.
|Santostasi, Giovanni; Malkani, Roneil; Riedner, Brady et al. (2016) Phase-locked loop for precisely timed acoustic stimulation during sleep. J Neurosci Methods 259:101-14|
|Peek, Clara Bien; Levine, Daniel C; Cedernaes, Jonathan et al. (2016) Circadian Clock Interaction with HIF1Î± Mediates Oxygenic Metabolism and Anaerobic Glycolysis in Skeletal Muscle. Cell Metab :|
|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|
|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|
|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|
|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; Van Cauter, Eve (2016) Disturbances of sleep and circadian rhythms: novel risk factors for obesity. Curr Opin Endocrinol Diabetes Obes 23:353-9|
|Perelis, M; Ramsey, K M; Bass, J (2015) The molecular clock as a metabolic rheostat. Diabetes Obes Metab 17 Suppl 1:99-105|
|Perelis, Mark; Marcheva, Biliana; Ramsey, Kathryn Moynihan et al. (2015) Pancreatic Î² cell enhancers regulate rhythmic transcription of genes controlling insulin secretion. Science 350:aac4250|
|Westerberg, Carmen E; Florczak, Susan M; Weintraub, Sandra et al. (2015) Memory improvement via slow-oscillatory stimulation during sleep in older adults. Neurobiol Aging 36:2577-86|
Showing the most recent 10 out of 194 publications