SuperAgers, a group of adults over 80 with memory performance comparable to people in their 50s, have been found to generate at least twice as many new neurons in the hippocampus compared to typical older adults and even younger individuals. This discovery comes from a study led by researchers at the University of Illinois Chicago (UIC), who examined brains donated through the Northwestern University SuperAger Program.
The study is the first to identify a genetic difference between SuperAgers and other older adults. Previous research over more than 25 years at Northwestern has documented biological and behavioral differences in SuperAgers, such as slower cortical thinning and stronger social engagement. The latest findings were published in Nature.
“We’ve always said that SuperAgers show that the aging brain can be biologically active, adaptable, flexible, but we didn’t know why,” said Tamar Gefen, associate professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and neuropsychologist at Northwestern’s Mesulam Institute for Cognitive Neurology and Alzheimer’s Disease. “This is biological proof that their brains are more plastic, and a real discovery that shows that neurogenesis of young neurons in the hippocampus may be a contributing factor.”
While animal studies have shown ongoing neurogenesis—the creation of new neurons—evidence for this process in humans has been inconsistent. This research confirms that neurogenesis does occur in healthy human adults. It also reveals that SuperAgers produce two to two-and-a-half times more new neurons than both healthy peers and those with Alzheimer’s disease. The scientists found a unique “resilience signature” in the hippocampi of SuperAgers—a distinct cellular environment supporting neuron birth and survival.
“This is a big step forward in understanding how the human brain processes cognition, forms memories and ages,” said Orly Lazarov, corresponding author on the study, professor at UIC College of Medicine, and director of UIC’s Alzheimer’s Disease and Related Dementia Training Program. “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.”
Researchers also discovered changes in two types of brain cells—astrocytes and CA1 neurons—that are linked to cognitive resilience as people age.
“What’s emerging from this study is this idea that SuperAgers are, in general, very distinct,” said Changiz Geula, research professor at the Mesulam Institute. “The genetic programs that support brain cell survival and communication stay on in SuperAgers in these cells, but they’re switched off in Alzheimer’s disease.”
The results suggest preserving excitatory synapses—the main sites for neuronal communication involved with memory formation—could be an effective target for drugs aiming to prevent cognitive decline.
To conduct their analysis, scientists studied hippocampal tissue from five groups: healthy young adults; older adults without cognitive impairment; older adults with mild or early dementia; older adults diagnosed with Alzheimer’s disease; and SuperAgers. They used multiomic single-cell sequencing on nearly 356,000 individual cell nuclei from these samples to examine gene activity as well as DNA accessibility across different stages of neuron development.
Northwestern authors Ivan Alejandro Ayala, Dr. Sandra Weintraub, and Dr. Marek Marsel Mesulam contributed to this work. Funding was provided partly by the National Institute on Aging within the National Institutes of Health.
