Sleep in older people is marked by difficulty with initiation, frequent arousals, and early awakening. While the consequences of acute sleep deprivation have been investigated in older people, very little is known about the consequences of the chronic insufficient sleep experienced by many older people. Moreover, the interaction between the misalignment of circadian phase, so common in older people, and chronic insufficient sleep has not been studied. Our proposal seeks to address that gap in our knowledge by using a well-established laboratory model to study what differences may exist between the sleep efficiency of older and younger subjects under conditions of chronic sleep restriction (ratio 19 hours scheduled wake: 5 hours scheduled sleep), carried out on a forced-desynchrony protocol, and by assessing the recuperative capabilities under conditions of sleep extension following this restriction. The design of our human subjects protocol provides a tremendous opportunity to investigate an array of cognitive performance measures under these conditions of chronic sleep restriction and subsequent sleep extension. The Polysomnography Core of the proposed Program Project will provide accurate and reliable scoring of polysomnographic recordings from subjects participating in the experimental protocol as well as from prospective subjects during the screening process. A 'metabolic aging' experiment has been included in our proposal with the goal of understanding the endocrine and cardiovascular consequences of sleep restriction in both young and older subjects. In the previous cycle of this Program Project, it was hypothesized that sleep difficulties in older people might be due to loss of neurons in the ventrolateral preoptic nucleus (VLPO). A critical component of this proposal is the continued pursuit of this mammalian model for sleep regulation during aging. With aging, there is a loss of neurons in the ventrolateral preoptic nucleus (VLPO), which is necessary for normal sleep, with aging, and we hypothesize that rats with partial lesions of the VLPO are a high fidelity model for sleep in older people. We will test this model for its validity for older people by performing a series of studies that parallel the human components of this Program Project grant, both in older rats and in rats with partial VLPO lesions. We hypothesize that the VLPO lesioned rat is a good model for sleep in older people who have VLPO cell loss, and to use this model to test the efficacy of treatment designed to restore VLPO function, which we hope will restore sleep as well as improve cognitive and motor skills that deteriorate with aging and poor sleep. The core components - Administrative, Analytic and Polysomnography - are effective in providing support across projects and most importantly, providing for cohesion of efforts across the entire Program Project. The results of this research will have important implications for understanding the role of sleep in the health, safety, and neurocognitive functions of older people. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
2P01AG009975-11
Application #
7076758
Study Section
Special Emphasis Panel (ZAG1-ZIJ-2 (J2))
Program Officer
Monjan, Andrew A
Project Start
1991-08-01
Project End
2011-06-30
Budget Start
2006-09-01
Budget End
2007-06-30
Support Year
11
Fiscal Year
2006
Total Cost
$1,166,643
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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
Gottlieb, Daniel J; Ellenbogen, Jeffrey M; Bianchi, Matt T et al. (2018) Sleep deficiency and motor vehicle crash risk in the general population: a prospective cohort study. BMC Med 16:44
Biello, Stephany M; Bonsall, David R; Atkinson, Lynsey A et al. (2018) Alterations in glutamatergic signaling contribute to the decline of circadian photoentrainment in aged mice. Neurobiol Aging 66:75-84

Showing the most recent 10 out of 208 publications