SuperAgers: Study Reveals Brains of Exceptionally Sharp Seniors Grow More Neurons
Individuals with remarkably sharp minds in their 80s and 90s – often referred to as “SuperAgers” – produce twice the number of new neurons compared to cognitively healthy adults, and 2.5 times more than those with Alzheimer’s disease, according to a new study published this week in Nature.
This finding, , underscores the brain’s capacity for regeneration even in advanced age, a concept that has significant implications for understanding and potentially preventing cognitive decline. “This shows the aging brain has the capacity to regenerate – that’s huge,” said 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 mature neurons are relatively stable, younger neurons are more adaptable and plastic, possessing an enhanced ability to grow, integrate, and form connections within the brain, explained Dr. Gefen, who also co-leads the Northwestern SuperAging Program. Researchers at Northwestern have been studying individuals with superior memories for 25 years, seeking to understand the biological basis of their resilience.
“SuperAgers are showing the preservation of immature neurons with heightened excitability – they are bright-eyed and bushy-tailed and ready to fire,” Dr. Gefen stated. “That is a more youthful brain.” The study also revealed that SuperAger brains contain more robust support systems within the hippocampus – the brain region crucial for memory – that nurture these youthful neurons, much like providing a young plant with nutrient-rich soil.
“This research shows SuperAgers have a unique cellular environment in their hippocampus which supports neurogenesis,” Dr. Gefen added. “This is biological proof SuperAgers have more plastic brains.” Neurogenesis, the birth and survival of new neurons, directly enhances brain plasticity – the brain’s ability to repair itself and maintain cognitive function in the face of aging and injury.
Interestingly, the brains of SuperAgers contained more newly developed neurons than those of healthy young adults aged 30 to 40, according to lead author Orly Lazarov, a professor of neuroscience and director of the Alzheimer’s Disease and Related Dementias Training Program at the University of Illinois, Chicago.
“The neurogenesis profile in SuperAgers shows resilience,” Lazarov said. “So they can cope with the ravages of time.”
The study utilized a technique called single-cell multiomic sequencing, allowing researchers to determine which brain cell types support memory and cognition as the hippocampus ages. The analysis of brain tissue from five groups – SuperAgers, healthy young adults, older adults with no cognitive impairment, older adults with early-stage dementia, and those diagnosed with Alzheimer’s disease – revealed that two cell types, astrocytes and CA1 neurons, were key drivers of memory retention in SuperAgers.
CA1 neurons are critical for memory consolidation and recall, and are among the first brain cells affected by tau tangles in Alzheimer’s disease. Astrocytes, which outnumber neurons, regulate blood flow to the brain and promote the formation of synapses – the junctions where nerve signals pass between neurons, forming the foundation of brain function, learning, and memory.
In SuperAgers, astrocytes and CA1 neurons appear to support the hippocampus in ways previously not understood, enhancing synaptic signaling between neurons. “The immature neurons, the CA1 circuits, and the astrocytes are all coordinating in a very, very enriched environment,” Dr. Gefen explained.
Previous research on neurogenesis in humans has been limited, in part due to the tools used for measurement. This new study provides a more detailed understanding of the cellular mechanisms underlying cognitive resilience in aging. The findings suggest that SuperAgers may have a genetic predisposition, but lifestyle factors also play a role in maintaining brain health, according to 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 that lifestyle changes, including diet, exercise, stress reduction, and optimizing sleep, along with managing vascular risk factors with certain prescription medications, can also grow areas of the brain, including the hippocampus, and reduce hallmarks of Alzheimer’s like tau tangles and amyloid plaques,” Dr. Isaacson said.
“It certainly was never taught to me in medical school that it’s possible for brain cells to grow, but now we’ve seen compelling evidence of this in serial MRIs in people who consistently make healthy brain choices,” he added.
To qualify as a “SuperAger,” an individual must be over 80 years old and undergo comprehensive cognitive testing to assess their memory capabilities, according to Emily Rogalski, a professor of neurology at the University of Chicago, who 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 note that when we compare SuperAgers to people of average age, they have similar IQ levels, so the differences we’re seeing aren’t just due to intelligence.”
SuperAgers also tend to share common traits. They are often optimistic and actively challenge their brains through reading or learning new things. Many remain physically active and continue working into their 80s. They are also highly social, surrounded by family and friends, and frequently engage in volunteer work within their communities.
However, even among SuperAgers, there is variability in healthy behaviors. “We have SuperAgers with heart disease, diabetes, who aren’t physically active, who don’t eat better than their age-matched peers,” Dr. Gefen noted. “Yet, what we’ve found in brains donated by SuperAgers is the most revealing.”
Analysis of brain tissue revealed that the cingulate cortex, an area responsible for attention, motivation, and cognitive engagement, is thicker in SuperAgers compared to individuals in their 50s and 60s. The hippocampus of SuperAgers also contained three times fewer tau tangles, a hallmark of Alzheimer’s disease. Another study found “beautiful, enormous, very healthy” neurons in the entorhinal cortex of SuperAgers, one of the first brain areas affected by Alzheimer’s disease.
“It was an incredible finding, because their entorhinal neurons were even larger than those of much younger people, some even in their 30s,” Dr. Gefen said. “That indicated to us that there is a component of structural integrity at play. Like architecture, the bones, the skeleton of the neuron itself is more resilient.”
The new study sheds light on how this might occur. The enhanced environment within the hippocampus appears to be supporting and nourishing immature brain cells. The findings highlight the interconnectedness of these cellular processes and provide a mechanistic understanding of why SuperAgers may maintain cognitive resilience.