Stem cells hold great promise for treating many age-related disorders through cell replacement therapy, yet little is known about the ability of aged tissue to support critical events in the survival, spatial targeting, or differentiation of grafted stem cells or primitive progenitor cells. In the central nervous system, an age-related decline in neurogenesis in the dentate gyrus has been reported. We have recently found a massive decline in neurogenesis in the aged olfactory bulb, the other region supporting neurogenesis in the adult brain. Therefore, the environment of the aging brain may be impaired for supporting differentiation and integration of either endogenous or grafted stem cells. In this regard, comparison of aging brain with young brain may provide a useful model to discriminate between critical environmental factors regulating neurogenesis and supporting neuronal differentiation. Identifying such age-related deficits and restoring their expression in the aged brain would be necessary to extend the possible use of cell replacement strategies for treating age-related neurodegeneration, stroke, or cognitive decline. Alternatively, the environment of the aging brain may retain adequate neuronal differentiation signals in these neurogenic regions, but the endogenous stem cells may exhibit age-related impairment in their ability to differentiate. This project will test these two possibilities by 1) evaluating differences in expression of identified stem cell proliferation and differentiation signals between young and aged adult brain and 2) restoring expression of deficient signals by gene delivery to enhance neurogenesis in the aged brain. The subsequent grafting of rodent stem cells derived from embryonic, young adult and aged adult tissue sources will reveal the extent to which environmental modification of aged tissue can facilitate effective cell replacement therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG022555-01
Application #
6676120
Study Section
Special Emphasis Panel (ZRG1-BDCN-2 (01))
Program Officer
Wise, Bradley C
Project Start
2003-09-15
Project End
2008-08-31
Budget Start
2003-09-15
Budget End
2004-08-31
Support Year
1
Fiscal Year
2003
Total Cost
$371,025
Indirect Cost
Name
Rosalind Franklin University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
069501252
City
North Chicago
State
IL
Country
United States
Zip Code
60064
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Bernal, Giovanna M; Peterson, Daniel A (2011) Phenotypic and gene expression modification with normal brain aging in GFAP-positive astrocytes and neural stem cells. Aging Cell 10:466-82
Marr, Robert A; Thomas, Rosanne M; Peterson, Daniel A (2010) Insights into neurogenesis and aging: potential therapy for degenerative disease? Future Neurol 5:527-541
Lazarov, Orly; Mattson, Mark P; Peterson, Daniel A et al. (2010) When neurogenesis encounters aging and disease. Trends Neurosci 33:569-79
Bernal, Giovanna M; Peterson, Daniel A (2004) Neural stem cells as therapeutic agents for age-related brain repair. Aging Cell 3:345-51
Peterson, D A (2004) Stem cell therapy for neurological disease and injury. Panminerva Med 46:75-80
Peterson, Daniel A (2004) Umbilical cord blood cells and brain stroke injury: bringing in fresh blood to address an old problem. J Clin Invest 114:312-4