Superagers show greater neuron growth linked to strong memory

Brains of older adults with super healthy cognition grow more new neurons than those of their peers, according to a study from UIC, Northwestern University and the University of Washington. Researchers found that the brains of superagers – octogenarians with uncommonly nimble minds – were the most neuronally fertile, while those with Alzheimer’s disease had negligible new growth.

This is a big step forward in understanding how the human brain processes cognition, forms memories and ages. 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.”

Orly Lazarov, professor in UIC’s College of Medicine and director of the Alzheimer’s Disease and Related Dementia Training Program

Neurons, or brain cells, support almost every human function. When you wiggle a toe or snap a finger, a neuron zaps a signal from your brain to your nervous system. In the latter half of the 20th century, researchers determined that new neurons could spawn throughout the lifespan in the brain’s hippocampus, or memory center – a phenomenon called adult neurogenesis. 

At first, scientists observed neurogenesis in rodents and were skeptical about whether it would appear in other mammals. Then, studies in primates linked neurogenesis to healthier aging brains, particularly stronger memory formation and processing.

This recent study, published in Nature, affirms that neurogenesis occurs in adult humans as well. 

The researchers looked at donated brain samples from five groups: healthy young adults; healthy older adults; older adults with exceptional memory, or superagers; individuals with mild or early dementia; and those diagnosed with Alzheimer’s disease.

The superager brains in the samples came from donors aged 80 years or older with exceptional memory skills. Brain samples from superagers were obtained from Northwestern University. The University of Washington supplied all other samples.

The researchers searched for three stages of developing neurons in the brains’ hippocampi: stem cells, which could potentially evolve into neurons; neuroblasts, adolescent stem cells on their way to neuronhood; and immature neurons, which are just shy of becoming functional.

“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 hippocampal neurogenesis, or the formation of new neurons in the hippocampus, does indeed occur in healthy human adults. Further, superagers actively produced more new neurons than their counterparts – their distinct “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 preclinical cognitive decline – the earliest stage of cognitive decline, before symptoms start to appear – displayed minimal neurogenesis. Those diagnosed with Alzheimer’s disease generated almost no new neurons.

Further, the researchers observed that the new neurons had different epigenetic signatures – or blueprints for responding to environmental change – depending on the brains’ cognitive health.

“Modern medicine has revolutionized health care such that life expectancy is greater now than ever before,” said co-lead author Dr. Jalees Rehman, the Benjamin J. Goldberg Professor and head of the department of biochemistry and molecular genetics at UIC. “We need to ensure that this overall increased life expectancy goes along with a high quality of life, including cognitive health.” 

Rehman said that understanding the full molecular picture of neurogenesis and its epigenetic signature can inform targeted therapeutics to preserve memory and cognitive function in aging adults. Next, this team will examine environmental and lifestyle factors – like diet, exercise and inflammation – that may work alongside neurogenesis to impact aging.

“What’s exciting for the public is that this study shows the aging brain is not fixed or doomed to decline,” said Ahmed Disouky, the first author of the study. “Understanding how some people naturally maintain neurogenesis opens the door to strategies that could help more adults preserve memory and cognitive health as they age.”

Additional UIC coauthors include Mark Sanborn, K. R. Sabitha, Mark Maienschein-Cline and Mostafa Mostafa from the College of Medicine.

Brain and tissue samples were obtained from the University of Washington Alzheimer’s Disease Research Center, the Adult Changes in Thought study, the Pacific Northwest Brain Donor Network, the Allen Institute for Brain Science, the Northwestern University Alzheimer’s Disease Research Center, the SuperAging Research Initiative, the Karen Toffler Charitable Trust and the Gefen-Querrey Brain Health Fund. The study was supported by the National Institute on Aging awards AG033570, AG033570-S2, AG076940, AGO79002, AG060238, AG061628 and AG091545.