October 6, 2004 -- 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 was published on 9 June 2004 as an advance online publication of the journal Nature.
One of the study's more surprising results 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 Yankner and colleagues examined patterns of gene expression in postmortem samples collected from 30 individuals ranging in age from 26 to 106 years. Using a 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.
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.
Lu T, et al. Gene regulation and DNA damage in the aging human brain. Nature 2004 Jun 24;429(6994):883-91.