Groundbreaking research by Israeli and American scientists suggests that the brains of “SuperAgers” may grow more new neurons than those of their peers.

Adults over the age of 80 who can recall everyday events and their past personal history just as well as cognitively normal people in their 50s and 60s are considered SuperAgers.

The peer-reviewed findings could pave the way for designing therapeutics for healthy aging, the researchers said.

The study, published in the journal Nature, was led by Orly Lazarov, a professor in the University of Illinois Chicago’s College of Medicine and director of the Alzheimer’s Disease and Related Dementia Training Program, who earned her PhD at Israel’s Weizmann Institute of Technology.

Other researchers include Tamar Gefen, associate professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine, who also works as a neuropsychologist at Northwestern’s Mesulam Institute for Cognitive Neurology and Alzheimer’s Disease, and scientists from the University of Washington.

“We’ve always said that SuperAgers show that the aging brain can be biologically active, adaptable, flexible, but we didn’t know why,” Gefen said, according to a statement by the universities.

The scientists found that SuperAgers produce twice as many new neurons as their healthy peers, and two and a half times as many as peers with Alzheimer’s disease. This could help explain why their memory stays strong with age.

The researchers also discovered a distinct “resilience signature” in the hippocampus of SuperAgers that supports the birth and survival of new neurons.

“This is a big step forward in understanding how the human brain processes cognition, forms memories, and ages,” said Lazarov. “Determining why some brains age more healthily than others can help researchers make therapeutics for healthy aging, cognitive resilience, and the prevention of Alzheimer’s disease and related dementia.”

Studying the hippocampus in postmortem brains

The scientists examined donated brain samples from five groups: healthy young adults, healthy older adults, individuals with mild or early dementia, those diagnosed with Alzheimer’s disease, and SuperAgers.

The SuperAger brains in the samples came from donors aged 80 years or older with exceptional memory skills.

Using an advanced single-cell technique called multiomic single-cell sequencing, the researchers examined nearly 356,000 individual cell nuclei from the hippocampus region.

This technique allowed the researchers to read both gene activity and the accessibility of DNA, enabling them to identify different stages of developing brain cells, including progenitor cells (early descendants of stem cells), immature neurons, and mature neurons.

“Think of the stages of adult neurogenesis like a baby, a toddler, and a teenager,” Lazarov said. “All are signs that these hippocampi are growing new neurons.”

Results indicated that the formation of new neurons in the hippocampus does indeed occur in healthy human adults. Also, SuperAgers actively produced more new neurons than their counterparts. It was their “resilience signature.”

“SuperAgers had twice the neurogenesis of the other healthy older adults,” Lazarov said. “Something in their brains enables them to maintain a superior memory. I believe hippocampal neurogenesis is the secret ingredient, and the data support that.”

Brain samples from individuals with the earliest stage of cognitive decline, before symptoms start to appear, displayed minimal neurogenesis, while those diagnosed with Alzheimer’s disease generated almost no new neurons.

“There has been a long entrenched common belief that brain cells do not renew,” said Ilia Stambler, PhD, chairman and CSO of Vetek (Seniority) Association – The Movement for Longevity and Quality of Life, Israel. Stambler was not involved in the study.

However, he said that there has been “accumulating evidence” of the crucial role of neurogenesis for the past 20 years.

“This new research provides additional evidence for the role of neurogenesis in cognitive resilience, especially that of SuperAgers who retain remarkable physical and cognitive ability to extreme old age,” Stambler said.

The study offers a “new promise” for improving early diagnosis of cognitive impairment, he said. “And it offers perhaps the strongest hope for all of us that healthy longevity can be reached.”

In their study, the scientists said they found a specific biological pattern in the hippocampus that showed the difference between staying cognitively active and losing mental ability during aging.

The study is the first to identify a genetic difference between the brains of SuperAgers and typical older adults, the researchers said.

“This is biological proof that their brains are more plastic,” said Gefen, “and a real discovery that shows that neurogenesis of young neurons in the hippocampus may be a contributing factor.”

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