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UK Study Offers More Complex Model
of Brain Aging

Contact: Jennifer Bonck

 

The report appears in the May 2003 issue of The Journal of Neuroscience. It provides more information about genes already linked to aging, including some involved in inflammation and oxidative stress, and describes additional areas in which gene activity might play a role in brain aging. These include declines in energy metabolism in cells and changes in the activity of neurons (nerve cells) in the brain and their ability to make new connections with each other.

 

May 7, 2003 (Lexington, Ky.) -- A University of Kentucky study matching the activity of 146 genes with brain aging and impaired learning and memory produces a new picture of brain aging and cognitive impairment.

The research, headed by Philip W. Landfield, Ph.D., professor and chair, Department of Molecular and Biomedical Pharmacology, UK College of Medicine, uses powerful new gene microarray technology in a novel way to match gene activity with actual behavioral and cognitive performance over time. This method has resulted in the identification of a wide range of aging- and cognition-related genes (ACRG). The study indicates that the changes in gene activity appear to begin in mid-life, suggesting that changes in gene activity in the early adult brain might set off cellular or biological changes that could affect how the brain works later in life.

The report appears in the May 2003 issue of The Journal of Neuroscience. It provides more information about genes already linked to aging, including some involved in inflammation and oxidative stress, and describes additional areas in which gene activity might play a role in brain aging. These include declines in energy metabolism in cells and changes in the activity of neurons (nerve cells) in the brain and their ability to make new connections with each other.

In addition, other areas in which genes appear to play an influential role involve increases in cellular calcium levels that could trigger cell death, cholesterol synthesis (also implicated in Alzheimer’s disease in other research), and iron metabolism. Genes also may play a large role in the breakdown of the insulating myelin sheaths that normally allow for efficient communication among nerve cells.

“Gene microarrays, which can measure activity of thousands of genes simultaneously, provide the most advanced genomics technology. This has allowed us to do what no other study has done before – use large numbers of microarrays in a new strategy to relate genes and behavior over the lifespan of the animals on a scale that can identify most of the important players,” said Landfield. “The good news is that we have a new, more comprehensive model of brain aging at the genetic level; the downside is that this model shows just how very complex that process may be. Nonetheless, this detailed picture should allow us to develop new therapeutic targets for cognitive impairment.”

Ultimately, the research team zeroed in on 146 ACRGs, which were assigned to functional categories representing different cellular processes in the brain. A complete listing of the genes and what they do appears in the journal article.

The research offers a new model of brain aging. In this model, a loss of nerve cell processes and the compromise of their insulating myelin sheaths may trigger brain inflammation, eventually leading to loss of cell function. The changes in gene expression for the most part are seen in mid-life, before cognition is impaired, suggesting that changes in gene activity in the brain in early adulthood might initiate cellular or biological changes that could lead to functional changes later in life. Aside from implicating such genetic networks in cognitive decline, the study also suggests new possible biological measures, or biomarkers, for tracking functional change in the aging brain.

The study was conducted by Landfield and colleagues Eric M. Blalock, Ph.D., research assistant professor; Kuey-Chu Chen, Ph.D., research assistant professor; Keith Sharrow, B.S., research associate; Thomas C. Foster, Ph.D., associate professor; and Nada M. Porter, Ph.D., associate professor, all of the Department of Molecular and Biomedical Pharmacology, UK College of Medicine, and James P. Herman, Ph.D., professor of psychiatry, University of Cincinnati College of Medicine. The research was supported primarily by the National Institute on Aging, with additional support from the National Institute of Mental Health, both divisions of the National Institutes of Health.


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