Insufficient sleep has been linked to adverse metabolic changes and increased risk of chronic disease including obesity, type 2 diabetes mellitus and early mortality. With age, most Americans increase visceral adiposity and become more likely to develop diabetes. Chronic insufficient sleep associated with 'normal aging'may be one of the factors involved in contributing to "metabolic aging'. Physiological changes in metabolism due to sleep loss for 1-2 weeks in young and middle-aged adults include reduced insulin sensitivity and hormonal changes that would increase the likelihood of obesity and diabetes in the long term. Our current data demonstrate that metabolic dysfunction occurs in young and older adults exposed to the combination of chronic sleep loss and recurrent circadian disruption for 3 weeks. Yet sleep loss experiments lengthen photoperiod, introducing a potential confounding effect on circadian rhythmicity, and circadian disruption itself has been shown to lead to adverse metabolic changes. Thus, the effects of sleep loss (with minimal circadian disruption) on glucose metabolism in older adults are not known. In Project 2, we will examine the metabolic responses to 3 weeks of sleep loss in a protocol with minimal circadian disruption to test the hypothesis that older adults will exhibit progressive decrements in total body and adipose tissue insulin sensitivity. We will determine the extent of the changes (glycemic responses to standardized meals, insulin sensitivity via euglycemic hyperinsulinemic clamps), the mechanisms of changes (via adipose tissue biopsy, sympathetic activation, and glucocorticoid activation) and the dynamics of changes (distinguishing effects over a few days and chronic effects over 3 weeks). Moreover, we hypothesize older adults will exhibit recovery of metabolic function with 1 week of sleep recovery. This Project will contribute to understanding the mechanisms by which sleep loss impairs metabolism in older adults, contributing to future research to reduce the risk of diabetes, improve existing therapies, and enhance the health and quality of life of older Americans whose sleep is insufficient.

Public Health Relevance

Sleep loss, common in aging, adversely impacts metabolism. We test to differentiate the multiple mechanisms by which sleep loss decreases total body and fat tissue insulin sensitivity in older adults. This research may aid in development of therapies to reduce the age-related risk of obesity and diabetes.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAG1-ZIJ-2 (M1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brigham and Women's Hospital
United States
Zip Code
Markt, Sarah C; Valdimarsdottir, Unnur A; Shui, Irene M et al. (2015) Circadian clock genes and risk of fatal prostate cancer. Cancer Causes Control 26:25-33
Balasubramanian, Ravikumar; Cohen, Daniel A; Klerman, Elizabeth B et al. (2014) Absence of central circadian pacemaker abnormalities in humans with loss of function mutation in prokineticin 2. J Clin Endocrinol Metab 99:E561-6
Dean 2nd, Dennis A; Adler, Gail K; Nguyen, David P et al. (2014) Biological time series analysis using a context free language: applicability to pulsatile hormone data. PLoS One 9:e104087
Hsieh, Wan-Hsin; Escobar, Carolina; Yugay, Tatiana et al. (2014) Simulated shift work in rats perturbs multiscale regulation of locomotor activity. J R Soc Interface 11:
Lim, Andrew S P; Ellison, Brian A; Wang, Joshua L et al. (2014) Sleep is related to neuron numbers in the ventrolateral preoptic/intermediate nucleus in older adults with and without Alzheimer's disease. Brain 137:2847-61
Lee, Jung Hie; Kim, Seong Jae; Lee, Se Yong et al. (2014) Reliability and validity of the Korean version of Morningness-Eveningness Questionnaire in adults aged 20-39 years. Chronobiol Int 31:479-86
Faghih, Rose T; Dahleh, Munther A; Adler, Gail K et al. (2014) Deconvolution of serum cortisol levels by using compressed sensing. PLoS One 9:e85204
Phillips, A J K; Fulcher, B D; Robinson, P A et al. (2013) Mammalian rest/activity patterns explained by physiologically based modeling. PLoS Comput Biol 9:e1003213
Breslow, Emily R; Phillips, Andrew J K; Huang, Jean M et al. (2013) A mathematical model of the circadian phase-shifting effects of exogenous melatonin. J Biol Rhythms 28:79-89
Phillips, A J K; Robinson, P A; Klerman, E B (2013) Arousal state feedback as a potential physiological generator of the ultradian REM/NREM sleep cycle. J Theor Biol 319:75-87

Showing the most recent 10 out of 128 publications