Is Brain Aging Inevitable? Despite Studies, Most Causes of Atrophy Remain a Mystery

From the first large studies monitoring the mental functioning of the same group of healthy humans over many years, scientists have uncovered unexpected results.

They report declines in some mental functions and improvements in others. In several studies, the speed of carrying out certain tasks becomes slower, but vocabulary improves. Other findings demonstrate less-severe declines in the type of intelligence relying on learned or stored information compared with the type that depends on the ability to deal with new information.

This research is supported by animal studies in which scientists find that changes in mental function are subtle. For example, in rodents and primates with only minor detectable brain abnormalities, certain spatial tasks, such as navigating to find food, tend to become more difficult with age.

It is also becoming clear that the aging brain is only as resilient as its circuitry. Scientists debate whether this circuitry is changed by neuron atrophy alone or whether some neuron loss over time is inevitable. In any event, when the circuitry begins to break down, remaining neurons can adapt by expanding their roles, and larger portions of the brain can be recruited so that older people can reach performance levels similar to those of younger adults.

In addition, learning conditions may dictate what happens to brain cells. Studies of rats shed light on some of the changes that occur in brain cells when the animals live in challenging, stimulating environments. Middle-aged rats exposed to such environments formed more and longer dendrite branches in the cerebral cortex than did rats housed in isolated conditions. In response to enriched environments, older rats tend to form new dendrite outgrowths and synapses, just as younger animals do. But the response is more sluggish and not as large. Compared with younger rats, older rats have less growth of the new blood vessels that nourish neurons.

Another study showed that, when rats were given acrobatic training, their brain cells had more synapses per cell than rats given only physical exercise or rats that were inactive. These findings led scientists to conclude that motor learning generates new synapses. Physical exercise alone, however, improved blood circulation in the brain. In humans, aerobic exercise can also improve cognitive performance.

Theories Abound

Despite these advances, most causes of normal brain aging remain a mystery. Dozens of theories abound. One says that specific ’aging genes’ are switched on at a certain time in life. Another points to the accumulation of genetic mutations or other types of DNA damage. Other researchers implicate hormonal influences or suggest that an immune system gone awry plays a central role in aging. Finally, many researchers advance a theory of brain aging that emphasizes the inexorable accumulation of oxidative damage caused by free radicals, cell byproducts that destroy fats and proteins vital to normal cell function.

As a logical consequence of this uncertainty about what causes normal brain decline, we are equally uncertain about what sustains healthy brain function as we grow older. Increasingly, both physical and mental exercise are viewed as effective means of slowing the effects of brain aging, perhaps by altering the levels of certain neurotropic factors that are beneficial to brain functioning.

Although much has been learned about the aging brain, many questions remain. For instance, does the production of proteins decline with age in all brain neurons? In a given neuron, does atrophy lead to a higher likelihood of death? How does aging affect gene expression in the brain, the organ with the greatest number of active genes? Do hormonal changes at menopause contribute to gender differences in brain aging?

Neuroscientists, too, speculate that certain genes may be linked to events leading to cell death in the nervous system. By understanding the biology of the proteins produced by genes, scientists hope to be able to influence the survival of neurons and develop ways to improve their functioning.

Our understanding of brain function has evolved over many years of research. Much of this research has been conducted with animals. In recent years, other technologies, such as imaging techniques, have emerged as powerful tools to reveal brain functioning in real time.

This article was prepared by the Society for Neuroscience.