Scientists discover a key to staying mentally sharp in old age
People who have razor-sharp minds in their 80s and 90s — known as “SuperAgers” — produce twice the number of young neurons as cognitively healthy adults and 2.5 times as many as people with Alzheimer’s disease, a new study found.
“This shows the aging brain has the capacity to regenerate — that’s huge,” said study coauthor Dr. Tamar Gefen, an associate professor of psychiatry and behavioral sciences at the Mesulam Institute for Cognitive Neurology and Alzheimer’s Disease at Northwestern University Feinberg School of Medicine in Chicago.
While a mature neuron is stable, a young neuron is the most adaptable and plastic type of brain cell, with an enhanced ability to grow, integrate and “wire itself into a brain,” said Gefen, who helps lead the Northwestern SuperAging Program. Researchers there have been studying elderly men and women with superior memories for 25 years.
“SuperAgers are showing the preservation of immature neurons with heightened excitability — they are bright-eyed and bushy-tailed and ready to fire,” she said. “That is a more youthful brain.”
In addition, the study found SuperAger brains contained more robust support systems in the hippocampus — the part of the brain responsible for memory — that nurture youthful neurons much like a young sapling is nourished when planted in nutrient-rich dirt.
“This research shows SuperAgers have a unique cellular environment in their hippocampus which supports neurogenesis,” Gefen said. “This is biological proof SuperAgers have more plastic brains.”
Neurogenesis, which is the birth and survival of new neurons, enhances brain plasticity — the ability of the brain to repair itself to maintain good cognitive function in the face of injury and the process of aging.
In fact, the brains of SuperAgers contained more newly developed neurons than 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 Dementia Training Program at the University of Illinois, Chicago.
“The profile of neurogenesis in the SuperAgers shows resilience,” Lazarov said in an email. “So they are able to cope with the ravages of time.”
SuperAgers may have a genetic advantage, but research shows that people who practice good brain health may also prevent cognitive decline, said Alzheimer’s prevention researcher Dr. Richard Isaacson, director of research at the Institute for Neurodegenerative Diseases in Florida, who was not involved in the study.
“Our studies have found lifestyle changes including diet, exercise, reducing stress and optimizing sleep, along with managing vascular risk factors with certain prescribed medications, can also grow brain areas including the hippocampus, and reduce telltale signs of Alzehimer’s such as tau tangles and amyloid plaques,” Isaacson said.
“I was certainly never taught in medical school that it’s possible for brain cells to grow, but we’ve now seen compelling evidence of this on serial MRI scans in people who continually make brain-healthy choices,” he said.
What is a ‘SuperAger’?
To be a “SuperAger,” a person must be older than 80 and undergo extensive cognitive testing that assesses the limits of their ability to recall information, Emily Rogalski, a professor of neurology at the University of Chicago, told CNN in an earlier interview. Rogalski, who was not an author on the study, helped develop the SuperAger program at Northwestern.
“SuperAgers are required to have outstanding episodic memory — the ability to recall everyday events and past personal experiences,” she said. “It’s important to point out when we compare the SuperAgers to the average agers, they have similar levels of IQ, so the differences we’re seeing are not just due to intelligence.”
SuperAgers also share similar traits. They tend to be positive and challenge their brain every day by reading or learning something new. Many are physically active and continue to work into their 80s. SuperAgers are also social butterflies, surrounded by family and friends, and they can often be found volunteering in their community.
When it comes to healthy behaviors, however, SuperAgers are a mixed bag.
“We have SuperAgers with heart disease, diabetes, who aren’t physically active, who don’t eat any better than their similar-age peers,” Gefen said. “Still, it’s what we’ve found in the brains donated by SuperAgers that is most telling.”
Analyses of brain tissue found the cingulate cortex, an area that’s responsible for attention, motivation and cognitive engagement, is thicker in SuperAgers compared with people in their 50s and 60s. The hippocampus of SuperAgers also has three times fewer tau tangles, one of the hallmarks of Alzheimer’s disease.
Another study found “beautiful, humongous, very healthy” neurons in the SuperAgers’ entorhinal cortex, one of the first areas of the brain to get hit by Alzheimer’s disease, Gefen said.
“It was an incredible finding, because their entorhinal neurons were even larger than those in individuals who are much younger, some even in their 30s,” she said. “That told us there is a structural integrity component at play — like the architecture, the bones, the skeleton of the neuron itself is sturdier.”
The new study sheds light on how that might occur, Gefen added.
“Those fat, juicy entorhinal neurons may not just be bigger, they may also be embedded in this enhanced ecosystem in the hippocampus that is also nurturing immature brain cells,” she said. “They are absolutely connected, and this new study may be providing a mechanistic understanding of why they may be bigger.”
A new way to measure neurogenesis
Past research in humans on how neurogenesis occurs has been murky, partly due to the type of measurement tools used, Lazarov said. The new study, published Wednesday in the journal Nature, used a different technique to measure the birth of new neurons in five types of donor brains: SuperAgers; healthy young adults; older adults with no sign of cognitive decline; older adults with early dementia; and older adults diagnosed with Alzheimer’s disease.
The tool, called multiomic single-cell sequencing, allowed researchers to determine which types of brain cells support memory and cognition as the hippocampus ages. Results showed two types of cells, astrocytes and CA1 neurons, were key drivers for memory retention in the brains of SuperAgers.
The CA1 neurons are crucial for memory, helping consolidate and retrieve past experiences. “These are among the first brain cells attacked by tau in Alzheimer’s disease,” Gefen said.
Astrocytes vastly outnumber neurons and are vital for regulating blood flow to the brain. These brain cells also encourage the formation of synapses, the junction where nerve signals pass from one neuron to another, which are the foundation of brain function, learning and memory.
“In SuperAgers, astrocytes and CA1 neurons are supporting the hippocampus in ways that we didn’t understand before, by boosting synapse signaling between neurons,” Gefen said. “Immature neurons, CA1 circuits and astrocytes are all coordinating in a very, very enriched environment.”