X-Message-Number: 24229
Date: Sat, 12 Jun 2004 16:12:08 +0200
Subject: Damaged Genes in Aging Human Brain Provide Clues to Cognitive Decline
From: David Stodolsky <>

Tue Jun  8 21:02:06 2004 Pacific Time


      Damaged Genes in Aging Human Brain Provide Clues to Cognitive 
Decline; Scientists Discover That Some Brains Age More Rapidly Than 
Others; Noticed Change After Age 40




         BOSTON, June 9 (AScribe Newswire) -- Unraveling the mysteries 
of the aging brain is a major goal for brain science, especially given 
the exploding population of senior citizens and the obvious desire to 
preserve brain function as long as possible.  Now, researchers at 
Children's Hospital Boston and Harvard Medical School have uncovered a 
kind of genetic signature associated with the aging human brain that 
may contribute to cognitive decline associated with aging. The study 
appears June 9 as an advance on-line publication of the journal Nature.

         One of the more surprising results of the study was that these 
gene changes start in the 40s for some individuals. The results raise 
intriguing questions about when and why the brain begins to age and the 
possibility of developing strategies to protect critical genes early in 
life in an attempt to preserve brain function and delay the onset of 
age-related conditions such as Alzheimer's disease.

         To investigate age-associated molecular changes in the human 
brain, Dr. Bruce A. Yankner, professor in the Department of Neurology 
and Division of Neuroscience at Children's Hospital Boston and Harvard 
Medical School, and colleagues examined patterns of gene expression in 
postmortem samples collected from thirty individuals ranging in age 
from 26 to 106 years. Using a sophisticated screening technique called 
transcriptional profiling that evaluates thousands of genes at a time, 
the researchers identified two groups of genes with significantly 
altered expression levels in the brains of older individuals.  A gene's 
expression level is an indicator of whether or not the gene is 
functioning properly.

         "We found that genes that play a role in learning and memory 
were among those most significantly reduced in the aging human cortex," 
said Yankner. "These include genes that are required for communication 
between neurons."

         In addition to a reduction in genes important for cognitive 
function, there was an elevated expression of genes that are associated 
with stress and repair mechanisms and genes linked to inflammation and 
immune responses.  This is evidence that pathological events may be 
occurring in the aging brain, possibly related to gene damage.

         The researchers then went on to show that many of the genes 
with altered expression in the brain were badly damaged and could not 
function properly. They showed that these genes also could be 
selectively damaged in brain cells grown in the laboratory, thereby 
mimicking some of the changes of the aging brain.

         "Our findings suggest that these genes are unusually 
vulnerable to damage from agents such as free radicals and toxins in 
the environment," said Yankner. "The brain's ability to cope with these 
toxic insults and repair these genes declines with age, leading to 
their reduced expression.  It will now be important to learn how to 
prevent this damage, and to understand precisely how it impacts brain 
function in the elderly."

         According to Yankner, "If you examine brain gene patterns 
among young adults, they are quite similar. In very old adults, there 
is some increased variability, but there is still similarity between 
individuals.  In contrast, individuals in the middle age population 
between 40 and 70 years of age are much more variable. Some middle-aged 
individuals exhibit gene patterns that look more like the young group, 
whereas others show gene patterns that look more like the old group."

         This is evidence that people may age differently during middle 
age. It will now be of great interest to understand what it is that 
makes some people age more rapidly than others.

         These findings raise the exciting possibility that treatments 
or lifestyles that reduce gene damage in young adults may delay 
cognitive decline and the onset of brain diseases in later years.  
However, more research is needed.

         "We can repair these aging genes in the laboratory, but that 
is a far cry from the human brain.  This is only a first step," 
cautions Yankner.

         Future directions of Dr. Yankner's lab include investigating 
whether these changes of normal aging are responsible for age-related 
conditions such as Alzheimer's and Parkinson's disease in some 
individuals. A major goal is the development of therapeutic approaches 
to preventing gene damage in the brain that could conceivably preserve 
cognitive function and prevent or delay the onset of neurodegenerative 
diseases. Along these lines, his lab is also interested in determining 
whether gene damage in the brain can be reversed after it occurs.

         The National Institute on Aging (NIA) and the National 
Institute of Neurologic Diseases and Stroke (NINDS) provided funding 
for this study.

         CONTACT: Susan Craig, CHB Public Affairs, 617-355-6420



David S. Stodolsky    SpamTo: 

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