NEURONAL STEM CELLS AND AGING (8 OF 11) Aging is associated with increased susceptibility to a variety of diseases and diminished capacity for tissue repair. Although many factors are likely to be involved, one proposed explanation for the less complete recovery from injury or disease that is often observed in aged individuals is impairment in the number or function of adult (tissue) stem cells. These cells persist throughout life in many tissues, where they may proliferate and differentiate in response to physiological cues and pathogenic insults. We hypothesize that although basal levels of neurogenesis decline with aging, the neurogenesis response to injury can be restored toward youthful levels for therapeutic purposes. Further, we anticipate that this is the case for both endogenous neurogenesis and neurogenesis from transplanted neuronal precursor cells (NPCs). Finally, we propose that the mechanisms responsible for the age-related decline in adult neurogenesis can be localized to one of two compartments: the NPCs themselves or the vascular niche in which they arise. We will test these hypotheses with the following specific aims: (1) Determine how aging alters injury-induced neurogenesis in the adult mouse brain;2) Examine whether age-related defects in injury-induced endogenous neurogenesis are imposed by neuronal precursor cells (NPCs) themselves or by their tissue environment;(3) Evaluate the extent to which the age of a recipient mouse determines the transplantation efficacy of human embryonic stem cell (hESC)-derived NPCs after injury; and (4) Identify candidate mediators of the age-induced decline in injury-induced endogenous neurogenesis by screening for changes in the proteome of endogenous NPCs and DG or SVZ endothelial cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Linked Research project Grant (RL1)
Project #
5RL1NS062414-04
Application #
7877720
Study Section
Special Emphasis Panel (ZRR1-SRC (99))
Program Officer
Owens, David F
Project Start
2007-09-30
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
4
Fiscal Year
2010
Total Cost
$432,135
Indirect Cost
Name
Buck Institute for Age Research
Department
Type
DUNS #
786502351
City
Novato
State
CA
Country
United States
Zip Code
94945
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