A new study finds that sharp-minded people in their 80s and 90s, known as “superagers,” produce twice as many young neurons as cognitively healthy adults and 2.5 times as many as Alzheimer’s disease patients.
“This shows that the aging brain has the capacity to regenerate—which is huge,” said study co-author Tamar Geffen, PhD, associate professor of psychiatry and behavioral sciences in Mesuram Cognitive Neurology and Alzheimer’s Disease Research Institute at Northwestern University Feinberg School of Medicine in Chicago.
While mature neurons are stable, young neurons are the most adaptable and plastic brain cell type, with an enhanced ability to grow, integrate and “wire themselves into the brain,” said Geffen, who helps lead the Northwestern Super Aging Project. For 25 years, researchers have been studying older men and women with exceptional memories.
“Superseniors show preservation of immature neurons and are highly excitable – they have bright eyes and bushy tails, ready to fire,” she said. “That’s a younger brain.”
In addition, research has found that the brains of super-aged people contain a stronger support system in the hippocampus (the part of the brain responsible for memory), which nourishes young neurons much like saplings are nourished in nutrient-rich soil.
“This study shows that super-elderly adults have a unique cellular environment in the hippocampus that supports neurogenesis,” Geffen said. “This is biological evidence that super-old people have more plastic brains.”
Neurogenesis, the birth and survival of new neurons, enhances brain plasticity—the brain’s ability to repair itself in the face of injury and the aging process to maintain good cognitive function.
In fact, the brains of super-old adults contain more newly developed neurons than those of younger adults in their 30s and 40s, said senior author Orly Lazarov, a professor of neuroscience and director of the Alzheimer’s Disease and Related Dementias Training Program at the University of Illinois at Chicago.
“Neurogenetic signatures in super-elderly adults show resilience,” Lazarov said in an email. “So they can cope with the ravages of time.”
Super old man undergoes cognitive testing in laboratory. – via Sean Collins/Northwestern University
Dr. Richard Isaacson, director of research at the Florida Institute for Neurodegenerative Diseases and an Alzheimer’s disease prevention researcher who was not involved in the study, said super-old people may have a genetic advantage, but research shows that people who maintain good brain health may also be protected against cognitive decline.
“Our study found that lifestyle changes, including diet, exercise, reducing stress and optimizing sleep, as well as using certain prescription medications to control vascular risk factors, can also promote growth in areas of the brain, including the hippocampus, and reduce signs of Alzheimer’s, such as tau tangles and amyloid plaques,” Isaacson said.
“I certainly was never taught in medical school that it was possible for brain cells to grow, but we are now seeing compelling evidence in serial MRI scans of people who have made brain-healthy choices,” he said.
What is a “super old man”?
Emily Rogalski, a professor of neurology at the University of Chicago, told CNN in an earlier interview that to become a “superager,” a person must be 80 years or older and undergo extensive cognitive testing to assess the limits of their ability to recall information. Rogalski, who was not an author of the study, helped develop the SuperAger project at Northwestern University.
“Super-old people need to have excellent episodic memory—the ability to recall daily events and past personal experiences,” she said. “It’s important to point out that when we compare superseniors to regular seniors, their IQ levels are similar, so the differences we see are not solely due to intelligence.”
Super seniors have similar characteristics. They tend to be active and challenge their brains every day by reading or learning something new. Many people are physically active and continue to work into their 80s. Superseniors are also social butterflies, surrounded by family and friends, and they often volunteer in their communities.
However, when it comes to health behaviors, the picture is mixed for superseniors.
“We have super-old people with heart disease, diabetes, who are not active and who don’t eat better than their peers,” Geffen said. “But what we found in the donated brains of super-elderly people is most telling.”
Analysis of brain tissue found that the cingulate cortex (the area responsible for attention, motivation and cognitive engagement) is thicker in super-old people compared with people in their 50s and 60s. The super-old people also had three times fewer tau tangles in their hippocampus, a hallmark of Alzheimer’s disease.
Another study found “beautiful, huge, very healthy” neurons in the entorhinal cortex of very old people, one of the first areas of the brain to be affected by Alzheimer’s disease, Geffen said.
“This was an incredible finding because their entorhinal neurons were even larger than those of much younger people, some as young as their 30s,” she said. “That tells us that there are structural integrity factors at play – things like the structure of the neurons themselves, the bones, the skeleton being stronger.”
Geffen added that the new study sheds light on how this happens.
“Those fat, juicy entorhinal neurons may not only be larger, they may also be embedded in this enhanced ecosystem in the hippocampus that is also nurturing immature brain cells,” she said. “They are absolutely related, and this new study may provide a mechanistic understanding of why they are larger.”
Researchers at Northwestern University have been studying the brains of super-elderly people for 25 years. – via Sean Collins/Northwestern University
New way to measure neurogenesis
Past research into how neurogenesis occurs in humans has been vague, Lazarov said, in part because of the types of measurement tools used. The new study, published Wednesday in the journal Nature, used a different technique to measure the birth of new neurons in the brains of five types of donors: healthy young adults; older adults with no signs of cognitive decline; older adults with early-stage dementia; and older adults diagnosed with Alzheimer’s disease.
This tool, called multi-omic single-cell sequencing, allows researchers to determine which types of brain cells support memory and cognition as the hippocampus ages. The results show that two types of cells, astrocytes and CA1 neurons, are key drivers of memory retention in the brains of super-elderly adults.
CA1 neurons are critical for memory, helping to consolidate and retrieve past experiences. “These are among the first brain cells to be attacked by tau in Alzheimer’s disease,” Geffen said.
Astrocytes, which far outnumber neurons, are critical in regulating blood flow to the brain. These brain cells also facilitate the formation of synapses, the connections where nerve signals pass from one neuron to another and are the basis of brain function, learning and memory.
“In super-elderly adults, astrocytes and CA1 neurons support the hippocampus in ways we didn’t previously understand by enhancing synaptic signaling between neurons,” Gefen said. “Immature neurons, CA1 circuits and astrocytes all coordinate in a very, very rich environment.”
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