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http://nia.nih.gov/news/pr/2003/0507.htm

National Institute on Aging - News Release

New Study in Rats Matches Genetic Influences and Cognitive Impairment,
Offers More Complex Model of Brain Aging 

A study in rats 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, by scientists at the
University of Kentucky, uses powerful new gene microarray technology
in a novel way to match gene activity with actual behavioral and
cognitive performance over time, resulting in the identification of
this wide range of aging- and cognition-related genes (ACRGs).
Importantly, the changes in gene activity had mostly begun in the
mid-life of the rats, suggesting that changes in gene activity in the
brain in early adulthood might set off cellular or biological changes
that could affect how the brain works later in life.            

 The report (embargoed for release until May 7, 2003, at 5 p.m. ET)
appears in the May 1, 2003, issue of The Journal of Neuroscience. It
provides more information on genes already linked to aging, including
some involved in inflammation and oxidative stress, and also 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 which could trigger cell death,
cholesterol synthesis (also implicated in Alzheimer�s disease in other
research), iron metabolism and the breakdown of the insulating myelin
sheaths that when intact facilitate efficient communication among
neurons.

The study was conducted by a team led by Philip W. Landfield, Ph.D.,
and colleagues Eric M. Blalock, Kuey-Chu Chen, Keith Sharrow, Thomas
C. Foster, and Nada M. Porter at the University of Kentucky,
Lexington, and James P. Herman at the University of Cincinnati, Ohio.
It was supported primarily by the National Institute on Aging (NIA).
Additional support was provided by the National Institute of Mental
Health (NIMH).  Both are parts of the National Institutes of Health at
the U.S. Department of Health and Human Services.

�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 to relate genes and behavior over the lifespan
of the animals on a scale that can identify most of the important
players,� says 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.� 

�This study makes it very clear that it is not a single gene or even
several genes that are responsible for brain aging. Here, we are
presented a picture of age-related changes in multiple cellular
pathways and systems which interact with one another to change the
brain�s structure and how it functions,� notes Brad Wise, Ph.D.,
Program Director, Fundamental Neuroscience, NIA.

 In the study, young, middle-aged, and aged rats were trained on two
memory tasks, learning to navigate a water maze and remembering
familiar objects in their cages.  After training, the scientists
examined the brain tissue of the rats, specifically the hippocampus,
an area associated with memory and cognition.  RNA (ribonucleic acid,
which carries out the DNA�s instructions for making proteins) was
isolated from each rat and selectively bound to a separate chip
containing over 8,700 fragments of genes to generate gene expression,
or activity, profiles. One important step was further refining of the
analyses to reduce false positives and false negatives while
statistically assessing changes in gene activity. The researchers then
homed in on genes that changed with aging and, finally, on genes
involved in age-related changes in the performance of the rats on the
two memory tests. Ultimately, they zeroed in on 146 ACRGs (aging- and
cognition-related genes), which were then assigned to functional
categories representing different cellular processes in the brain.  A
complete listing of the genes and what they do appears in the original
journal article.  

Offering one model of brain aging, the researchers suggest that loss
of neuronal processes and the compromise of their insulating myelin
sheaths may trigger brain inflammation, eventually leading to loss of
the cells� function. The changes in gene expression for the most part
were seen in mid-life, before cognition was 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. 

The NIA leads the Federal effort to support and conduct basic,
clinical, and social and behavioral studies on aging and on
age-related memory change and dementia.  It supports the Alzheimer�s
Disease Education and Referral (ADEAR) Center, which provides
information on research on age-related memory change and Alzheimer�s
disease.  ADEAR�s website can be viewed at www.alzheimers.org. ADEAR
may also be contacted at 1-800-438-4380.  Press releases, fact sheets,
and other materials about aging and aging research can be viewed at
the NIA�s general information website www.nia.nih.gov. 


  http://IanGoddard.net

  "To lengthen thy life, lessen thy meals." Ben Franklin

  Ongoing CR-monkey-study update: "In the monkeys...those on
  reduced feeding since the study started are dying at a rate 
  that is about half that of the monkeys receiving a full food
  ration." Associated Press: Eating less may extend human life.
  August 1, 2002 : http://www.msnbc.com/news/788746.asp?0si=-