By James Bakalar and Anthony L. Komaroff, M.D.
Newsweek
Are the changes in the brain that accompany aging caused by damage to the underlying genes involved in functions such as learning, memory and the transmission of nerve impulses? Exciting new research suggests that they may be, and the findings could eventually help predict and prevent degenerative brain diseases like Alzheimer's and Parkinson's.
A research team at Harvard Medical School studied changes in gene activity in the preserved brains of people who ranged in age from 26 to 106. Examining tissue from the prefrontal cortex, a center of higher mental functions, they uncovered some surprises. While most of the genes did not show changes with aging, about 4 percent became either more or less active. The differences in gene activity were caused by damage that occurred mainly in the regions of DNA that turn genes on, which are known as promoters. In most cases, the damage was caused by oxygen free radicals-hyperactive molecules released by the chemical reactions that power cells. Prominent among the genes that lost their youthful vigor were genes that affect learning and memory, cellular energy production and the transmission of impulses between brain cells. (To compensate for this oxidative injury, genes that protect tissues from oxidants and genes that repair DNA had become more active.)
The gene-promoter damage observed in the study began surprisingly early in life. While gene activity was similar in most brains from people in their 20s or 30s, problems became apparent in some brains as early as age 40. Also, the activity of learning and memory-related genes dropped faster in some people than in others, suggesting that each human brain ages in its own way. And occasionally the variations could be quite striking: one 71-year-old brain showed as much gene activity as that found in 30-year-old brains.
The biggest question raised by this study is why, in the course of normal aging, certain people are more vulnerable than others to age-related damage from oxygen free radicals. A second question is why genes important to memory and learning appear to be more vulnerable than other genes. Finding the answers could one day allow physicians to identify people at greatest risk for this kind of damage and to prevent it.
A better understanding of this normal aging process may also shed light on the beginnings of degenerative brain diseases like Alzheimer's and Parkinson's. "Looking at a brain afflicted by Alzheimer's disease is like looking at a battlefield after the war," says Dr. Bruce Yankner, a Harvard Medical School professor who led the study of brain-gene aging. "So much has been affected that it is difficult to know how it started. But by studying how the normal brain ages and comparing it with early cognitive decline, we hope to obtain clues to the earliest events in these diseases."
Bakalar is editor of the Harvard Mental Health Letter; Komaroff is editor in chief of the Harvard Health Letter.
