The Aging Brain
In recent years, scientists have mapped the human genome, explored the surface of Mars and developed crops that produce their own pesticides.
By contrast, much about the human brain still remains a mystery. That is particularly true when it comes to understanding how the brain ages.
Part of the mystery is due to the fact that, until recently, people did not have the same lifespan as they do today-now an average 75 years, up from 47 years in 1900. This means there has been precious little time to study brain aging, says David Walsh, Ph.D., associate professor of psychology. He says, “Theoretically, this is a whole new world.”
But research on how this three pound organ ages is speeding ahead-pushed by the fact that 10,000 U.S. baby boomers hit age 50 every day. This huge group, which will soon swell the ranks of senior citizens to previously unheard of proportions, wants to know what can be done to preserve brain function as long as possible.
After all, the brain is considered our most vital organ, responsible for everything from involuntary life support functions like heartbeats and breathing to the essence of personality and memory. It contains more than 100 billion cells including neurons-the specialized cells of the nervous system responsible for the transmission of electrical impulses to and from the central nervous system. Neurons can send signals to thousands of other cells at a rate of about 200 miles per hour. Just how these neurons work-a complicated system involving various chemicals (neurotransmitters) and electrical impulses-is only slowly coming to light.
Until recently, brain aging-and everything that entails, from the annoying inconveniences of age-related memory loss to more serious conditions like Alzheimer’s and dementia-was equated with neuron failure. “I think historically the subject was thought to be very simple: that brain neurons were lost from birth onwards,” explains Caleb Finch, Ph.D., the ARCO/William F. Kieschnick Chair in the Neurobiology of Aging and a professor of gerontology and biological sciences. “Now it is really clear that if you don’t have a specific disease that causes loss of nerve cells, then most, if not all, of the neurons remain healthy until you die. That’s a big change, and it has only come about in the last 10 years.”
One reason for the change: improved technology like higher resolution magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. These help scientists pinpoint the parts of the brain that function or fail as individuals age. The technology has also generated a wealth of information about the physical changes in the aging brain, including:
Brain weight and volume decrease. On average, the brain loses 5-10 percent of its weight between the ages of 20 and 90.
The grooves on the surface of the brain widen, while the swellings on the surface become smaller.
So-called “neurofibriallary tangles,” decayed portions of the branch-like dentricles that extend from the neurons, increase.
“Senile plaques,” or abnormally hard clusters of damaged or dying neurons, form.
Along with realizing these physical changes in the brain, one of the big surprises in recent years is data that suggests cognitive decline like age-related memory loss is not due to neuron loss, as previously thought. Instead, scientists now believe changes in function as we age have more to do with complex chemical interactions in the brain that occur over time.
For example, recent studies suggest plaques and tangles-long considered a cause of Alzheimer’s-may not turn out to be the culprits after all. A study in the Journal of Neurophysiology examined the brains of elderly people who were fully functioning up to their death and found them to have a large number of plaques and tangles that looked exactly like Alzheimer’s. But none of the subjects had displayed Alzheimer’s symptoms.
Instead, new research suggests Alzheimer’s may be connected to inflammatory processes associated with aging. Finch recently released findings of a new type of amyloid aggregates. Amyloid is a hard deposit that results from tissue degeneration, which forms in the presence of inflammatory proteins in the brain. The inflammatory proteins occur to a certain extent in all maturing adults, he notes. The soluble amyloid aggregates appear to form in the parts of the brain particularly affected by Alzheimer’s (including the hippocampus, the area responsible for forming new memory). Once there, they appear to interfere with the brain’s basic mechanism of long-term memory well before they reach a level high enough to kill brain cells, Finch says.
More evidence that brain aging is related to chemical changes in the brain comes from studies that suggest an age-related loss of dopamine, the brain chemical associated with pleasure and reward, slows metabolism in the regions of the brain related to cognition. Other research has explored conflicting data about the potential benefit of taking estrogen to reduce the risk of getting Alzheimer’s disease for post-menopausal women.
Further complicating the picture is that these changes do not happen to everyone at the same pace, notes Helena Chui, M.D., the Raymond and Betty McCarron Chair in Neurology. Chui is also co-director of the McCarron Clinical Research and Education Center, headquartered at the USC-affiliated Rancho Los Amigos National Rehabilitation Center in Downey, Calif. “Certain brain injuries occur suddenly, like a stroke or head injury. Neurodegenerative processes such as Alzheimer’s disease, on the other hand, occur gradually,” says Chui. “Furthermore, different people develop plaques and tangles at different rates. At some threshold, symptoms become noticeable. At this point, we don’t know all of the factors that determine these rates. Genetics, however, play an important role.”
The genetic influence on the rate of brain aging is the focus of new research. Jeff Victoroff, M.D., associate professor of clinical neurology at the Keck School and director of neurobehavior at Rancho Los Amigos, suggests, “Genetic evolution may have even favored those who, once they hit the old age of 35, retained the capacity to teach and provide emotional support rather than those whose brains’ limited resources were devoted to new learning.” In evolution 100,000 years ago, he says, “It was probably rare for people to live past age 40 or 50, which means there was very little evolutionary selective pressure to make the brain work when we’re 60 or 70 or 80. That’s probably why all brains decline with aging.”
What is most intriguing about the new findings in brain aging is that they indicate that the rate of change may be hastened or slowed by lifestyle factors. For instance, maintaining a lower weight might affect brain aging. As far back as the 1970s, Finch’s experiments with mice found that those on restricted diets had lower rates of brain aging disease like Alzheimer’s. Now, “We’re trying to understand how cutting back the food intake in rodents slows the inflammatory process,” Finch says. “I think one possibility is that it lowers blood glucose levels. Blood glucose is very reactive as a chemical and can cause damage to proteins.” The opposite condition is diabetes-a condition with elevated blood sugar-and, Finch says, those with diabetes typically show more signs of brain aging than non-diabetic individuals.
Other lifestyle factors that may affect brain aging:
Education: Those who ‘use it, don’t lose it’ as quickly, according to studies
that compare brain function in adults who attended college and those who did not. “We hesitate to say the brain is like a muscle. But using patterns of connectivity over and over and having those patterns prove useful to us in our life probably makes the synapses broader and the connections between neurons in these valuable and well-used systems stronger, “says Victoroff. One recent study showed that cognitive challenge actually created new neurons in the adult rodent brain, “which means that the old idea that mammals have all the neurons in the brain when born is probably wrong,” says Victoroff. “We expect to discover which environmental stimuli such as physical and mental exercise, are most likely to turn on new neurons in the adult brain.”
Exercise: Those who walk rapidly for as little as 45 minutes three times
a week significantly improve age-related declines in cognitive abilities, studies find.
Rest: There is new evidence that suggests a regular pattern of eight hours
of sleep per night helps protect against age-related chronic illnesses including memory loss.
Hypertension: Studies suggest hypertension speeds up normal brain
shrinkage and loss of mental abilities. Even those on antihypertensive medication have accelerated aging and shrinking of the brain.
Stress: When under stress, the human body produces a hormone called
cortisol. In small amounts, it can improve memory-which is what helps emotional events stay vividly in our minds. In larger amounts, however, it wears away at the neurons in the hippocampus.
Head trauma: It has long been known that boxers get punch drunk and
their brains exhibit changes that mimic Alzheimer’s disease, only much earlier, notes Finch. A new series of studies show that former soccer players have declines in cognitive function in proportion to their use of their heads in propelling the ball. “Here is a sport that is becoming increasingly popular. Are kids setting themselves up for early mental deterioration every time there’s a sharp blow to the head? That’s something that needs to be investigated,” Finch says.
Does this mean taking these specific steps will keep your brain in top condition? Although they acknowledge that genes play a large role in predetermining your brain’s aging, researchers are beginning to agree that taking care of your health might help your long term brain function. This topic is explored in Victoroff’s new book “Saving Your Brain,” which Bantam will publish in spring 2002. In the book, he suggests steps like strict control of blood pressure, blood sugar and cholesterol, diet, the use of certain vitamins, physical exercise and mental exercise to help keep the brain functioning at its peak. “These are probably things 15 year olds should be doing, because the effect on the brain is cumulative,” he says. “It certainly helps if someone in their 40s, 50s or even 70s starts to take the right steps, but the younger you are, the larger an impact it will have on delaying brain aging.”
Finch, Chui, Victoroff and others are optimistic that the future will bring better understanding-and treatment-of brain aging and its associated symptoms. Drugs now in preclinical or Phase I human trials to treat Alzheimer’s, says Chui, may decrease the levels of amyloids in the brain. Other experiments now underway suggest that deterioration in critical brain networks may be restored by gene therapy-transplanting brain cells genetically programmed to release a protein called nerve growth factor. The research focuses on a particular set of brain cells deep in the brain known as cholinergic neurons, which are shown to deteriorate rapidly in those with Alzheimer’s disease.
“Studies show that the human brain is built to go for an amazing length of time,” says Finch. Ten years from now, “we’ll have a greater understanding of the long-term risk factors that have adverse effects on the brain. We’ll know which people are more at risk earlier in their lives because of their genes. Knowing more about genes and the environment is not likely to yield a magic bullet, but each decade will nibble away at the adverse aspects of brain aging.”