Brain fibers lose 10% of their total length every decade. They can shrink even more so under acute stress. - FactzPedia


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Brain fibers lose 10% of their total length every decade. They can shrink even more so under acute stress.

Brain fibers lose 10% of their total length every decade

The hippocampus provided the gateway into much of what we have learned about stress and brain structural and functional plasticity, and this initial focus has expanded to other interconnected brain regions, such as the amygdala and prefrontal cortex. Starting with the discovery of adrenal steroid, and later, estrogen receptors in the hippocampal formation, and subsequent discovery of dendritic and spine synapse remodeling and neurogenesis in the dentate gyrus, mechanistic studies have revealed both genomic and rapid non-genomic actions of circulating steroid hormones in the brain. Many of these actions occur epigenetically and result in ever-changing patterns of gene expression, in which there are important sex differences that need further exploration. Moreover, glucocorticoid and estrogen actions occur synergistically with an increasing number of cellular mediators that help determine the qualitative nature of the response. The hippocampus has also been a gateway to understanding lasting epigenetic effects of early-life experiences. These findings in animal models have resulted in translation to the human brain and have helped change thinking about the nature of brain malfunction in psychiatric disorders and during aging, as well as the mechanisms of the effects of early-life adversity on the brain and the body

The human brain is big, and it's powerful, able to dream up innovative solutions to complex problems. Yet our brains don't age well: As we grow older, they tend to shrink and become increasingly vulnerable to cognitive dysfunctions such as memory loss and dementia. A new magnetic resonance imaging (MRI) study comparing humans and chimpanzees finds that chimp brains maintain their size as they age. Slowly losing our minds, it turns out, may be the evolutionary price we pay for having bigger brains and longer life spans.

Although few similar studies of other primates have been conducted, recent research with rhesus monkeys has shown only very limited shrinkage with age. Nevertheless, the evolutionary lineages leading to humans and rhesus monkeys diverged about 30 million years ago, leaving scientists in the dark about when the human pattern of brain aging might have begun.

To get a better idea, a team led by Chet Sherwood, an evolutionary neuroanatomist at George Washington University in Washington, D.C., directly compared the brain-shrinking patterns of chimps and humans, which diverged only about 5 million to 7 million years ago. The study sample included 87 humans ranging from ages 22 to 88, and 69 chimps from ages 10 to 51. Since chimps rarely live longer than 45 years in the wild—although a few in captivity have survived into their 60s—the sample represents the normal life span of both species.

For example, the gray matter of the human frontal lobe shrank an average of about 14% between the age of 30 and 80, and the gray matter of the hippocampus about 13% over the same period. But shrinkage of white matter was even more severe: The white matter of the frontal lobe shrank about 24%, similar to the white matter volume decrease in most other brain regions measured.

Moreover, unlike the gray matter, which showed a more gradual shrinkage over time, the decline in white matter was most precipitous between the ages of 70 and 80. So although the average decline in the frontal lobe was 24% at age 80, it was only about 6% at age 70.

So why do chimpanzees make it through their entire normal life spans without significant brain shrinkage, whereas the human brain appears to wither with age?

"This is the million-dollar question," Sherwood says. In the paper, the team points out that the larger human brain, which is more than three times as big as that of a chimp, also has much higher energy demands. Thus, the human brain uses up to 25% of the body's total available energy when we're at rest, compared with no more than about 10% for other primates.

The toll of keeping up with that energy supply, the team argues, shows up on the cellular and molecular levels in the human brain. This includes a decline in the efficiency of the mitochondria, the energy storehouses of living cells, as well as damage from oxidative stress, the result of oxygen-containing molecules that are produced during cell metabolism.

"My guess is that our neurons basically do the best they can to maintain maximal functioning for as long as they can," Sherwood says. "But they have the odds really stacked against them after long years of high energy consumption."

Dean Falk, an anthropologist at the School for Advanced Research in Santa Fe finds the differences between gray matter and white matter shrinkage patterns particularly interesting. White matter, which humans have relatively more of than chimps and other primates, "is particularly important for complex cognition in Homo sapiens," Falk says, because it makes the connections between brain regions involved in transmission of information during problem solving and other complicated tasks.

Nevertheless, Peter Rapp, a neurobiologist at the National Institutes of Health's Laboratory of Experimental Gerontology in Baltimore, Maryland, who carried out some of the earlier brain-imaging studies in rhesus monkeys, says that the new study does not distinguish between brain shrinkage as a consequence of normal aging in humans and shrinkage that might be due to neurodegenerative brain disease in a subset of the subjects. "Is what distinguishes chimps and humans susceptibility to disease, or a qualitative difference in the process of healthy brain aging?"

Bruce Yankner, a neurologist at Harvard Medical School in Boston, agrees. To test the authors' hypothesis that human brain shrinkage is a result of greater longevity, Yankner says, "it would be interesting" to see if similar brain shrinkage occurs in other species with extreme longevity, "such as tortoises and turtles that live for well over 100 years, elephants that can live for 70 years, and parrots that can live for 80 years."