The overall goal of this program of research is to investigate the mechanisms of, and consequences from, changes with sleep in older animals. The studies extend to evaluating changes in sleep in animal models of neurodegenerative disease and the mechanisms for these changes. To accomplish these goals, the program has 4 projects and 3 cores. The first project (Project Leader: A. Sehgal) uses Drosophila, which is increasingly becoming a model to study sleep mechanisms and aging. This project brings these two lines of study together and we propose to investigate the changes with sleep across the lifespan in Drosophila, whether such changes are mediated by oxidative mechanisms, and whether reduction of sleep amounts influences lifespan. Project 02 (Project Leader: A.I. Pack) is directed at the molecular functions of sleep and whether these funds are impaired in older animals. These studies are done in mice. Specifically, the project looks at the changes with sleep and wakefulness in regulation of protein translation and cholesterol synthesis and the role of alteration of activity of the AMP-dependent kinase in controlling these processes. Another aspect of the function of sleep is investigated in Project 03 (Project Leader: T. Abel). Dr. Abel looks, in mice, at the role of sleep in memory and whether this effect is reduced in older animals. Studies are proposed to investigate both the cellular and molecular mechanisms involved. In the final project, Dr. S. Veasey (Project Leader) studies mouse models of Alzheimer's disease. She proposes to study alterations in sleep in these mice and to determine the relationship with specific mechanisms affecting neurons involved in sleep/wake control. These four projects are supported by 3 cores: (A) Administrative Core, (B) Behavioral Assessment Core, and (C) Biostatistical and Data Base Core. Thus, these studies are directed at a common problem in older adults, i.e., disruption of sleep. The studies are directed at determining what causes this disruption and, moreover, what its consequences are in terms of how the brain functions. Studies are also proposed to determine if cutting back on sleep affects how long you live and why sleep is particularly disturbed in Alzheimer's disease. These studies have the potential to open up new avenues for treatment of sleep disruption in older adults.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG017628-09
Application #
7798128
Study Section
Special Emphasis Panel (ZAG1-ZIJ-2 (O1))
Program Officer
Wise, Bradley C
Project Start
1999-12-01
Project End
2012-03-31
Budget Start
2010-04-15
Budget End
2011-03-31
Support Year
9
Fiscal Year
2010
Total Cost
$1,539,725
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Tudor, Jennifer C; Davis, Emily J; Peixoto, Lucia et al. (2016) Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis. Sci Signal 9:ra41
Perron, Isaac J; Pack, Allan I; Veasey, Sigrid (2015) Diet/Energy Balance Affect Sleep and Wakefulness Independent of Body Weight. Sleep 38:1893-903

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