This is a multi-disciplinary investigation of the neurobiological changes that occur in the brain during normal aging. It consists of 3 cores and 4 projects that use the rhesus monkeys as an experimental model of normal human aging. To ate our studies have identified a pattern of age-related cognitive impairments in memory and executive function that first appear in late middle age (15 to 19) and become increasingly prevalent and severe from 20 years of age to the maximal life span of around 35. Examinations of the brains of cognitively tested monkeys reveals that neurons are not lost from the neocortex of hippocampus with age. But we have observed loss of white matter volume, morphological and receptors and reductions in markers of oxidative metabolism. All of these are sublethal which are the critical changes underlying the cognitive decline and what mechanisms produce these changes. But we have recently observed activated astrocytes and microglia in aged monkeys where they are most prominent deficits and what mechanisms produce these changes. But we have recently have observed activated astrocytes and microglia in aged monkeys where they are most prominent in white matter. Since activated glia can produce free radicals and inflammatory mediators that damage neurons, oligodendroglia and myelin, we will investigate our hypothesis that such inflammatory insult leads to sublethal damage to neurons and myelin, compromising cerebral function and causing cognitive declined. For these studies we will behaviorally test young adults 5 to 1o years of age, middle aged monkeys 15 to 19 years old and elderly monkeys over 20 and examine their brains using physiological, biochemical and morphological methods. One goal will be to identify those monkeys that are most cognitively impaired and those that are successfully aging in order to identify the constellation of changes that most strongly predict severe age-related cognitive decline. A second goal will be identify in the late middle aged monkeys those changes that occur first and may constitute precipitating events that initiate a cascade of neuropathological changes. These studies will allow us to account for age-related pathology in the brain and the resulting cognitive decline. In addition they will allow us to designing experimental and therapeutic interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
3P01AG000001-27S1
Application #
6649011
Study Section
Special Emphasis Panel (ZAG1 (M2))
Program Officer
Wagster, Molly V
Project Start
1975-06-01
Project End
2005-06-30
Budget Start
2002-09-01
Budget End
2003-06-30
Support Year
27
Fiscal Year
2002
Total Cost
$48,450
Indirect Cost
Name
Boston University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
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