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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG009975-17
Application #
8707296
Study Section
Special Emphasis Panel (ZAG1)
Project Start
2014-07-01
Project End
2018-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
17
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
Scheuermaier, Karine; Münch, Mirjam; Ronda, Joseph M et al. (2018) Improved cognitive morning performance in healthy older adults following blue-enriched light exposure on the previous evening. Behav Brain Res 348:267-275
Swanson, Christine M; Kohrt, Wendy M; Buxton, Orfeu M et al. (2018) The importance of the circadian system & sleep for bone health. Metabolism 84:28-43
Leise, Tanya L; Goldberg, Ariella; Michael, John et al. (2018) Recurring circadian disruption alters circadian clock sensitivity to resetting. Eur J Neurosci :
Zitting, Kirsi-Marja; Münch, Mirjam Y; Cain, Sean W et al. (2018) Young adults are more vulnerable to chronic sleep deficiency and recurrent circadian disruption than older adults. Sci Rep 8:11052
McHill, Andrew W; Hull, Joseph T; McMullan, Ciaran J et al. (2018) Chronic Insufficient Sleep Has a Limited Impact on Circadian Rhythmicity of Subjective Hunger and Awakening Fasted Metabolic Hormones. Front Endocrinol (Lausanne) 9:319
Li, Peng; Yu, Lei; Lim, Andrew S P et al. (2018) Fractal regulation and incident Alzheimer's disease in elderly individuals. Alzheimers Dement 14:1114-1125
Todd, William D; Fenselau, Henning; Wang, Joshua L et al. (2018) A hypothalamic circuit for the circadian control of aggression. Nat Neurosci 21:717-724
Naganuma, Fumito; Bandaru, Sathyajit S; Absi, Gianna et al. (2018) Melanin-concentrating hormone neurons contribute to dysregulation of rapid eye movement sleep in narcolepsy. Neurobiol Dis 120:12-20
Asgari-Targhi, Ameneh; Klerman, Elizabeth B (2018) Mathematical modeling of circadian rhythms. Wiley Interdiscip Rev Syst Biol Med :e1439
Kroeger, Daniel; Absi, Gianna; Gagliardi, Celia et al. (2018) Galanin neurons in the ventrolateral preoptic area promote sleep and heat loss in mice. Nat Commun 9:4129

Showing the most recent 10 out of 208 publications