The brains of cognitively healthy older adults grow more new neurons than their peers, according to a study from UIC, Northwestern University and the University of Washington. The researchers found that the brains of the super-elderly – octogenarians with unusually nimble minds – were the most neuronally fertile, while those with Alzheimer’s had negligible new growth.
This is a big step forward in understanding how the human brain processes knowledge, forms memories and ages. “Determining why some brains age more healthily than others can help researchers develop treatments for healthy aging, cognitive resilience, and the prevention of Alzheimer’s disease and related dementias.”
Orly Lazarov, UIC College of Medicine professor and director of the Alzheimer’s Disease and Related Dementia Education Program
Neurons or brain cells support almost every human function. When you wiggle a toe or snap a finger, a neuron sends a signal from your brain to your nervous system. In the second half of the 20th century, researchers determined that new neurons could be born throughout life in the brain’s hippocampus, or memory center—a phenomenon called adult neurogenesis.
At first, scientists observed neurogenesis in rodents and were skeptical that it would occur in other mammals. Subsequently, studies in primates linked neurogenesis to healthier aging brains, particularly stronger memory formation and processing.
This recent study, published in Natureconfirms that neurogenesis also occurs in adult humans.
The researchers examined brain samples donated by five groups: healthy young adults; healthy older adults; older adults with exceptional memory, or superagers. people with mild or early dementia. and those diagnosed with Alzheimer’s disease.
The aged brains in the samples came from donors aged 80 and over with excellent memory skills. Brain samples from superagers were obtained from Northwestern University. The University of Washington provided all other samples.
The researchers looked for three stages of neuron development in the brain’s hippocampus: stem cells, which could potentially develop into neurons; neuroblasts, adolescent stem cells on their way to becoming a neuron. and immature neurons, just shy of becoming functional.
“Think of the stages of adult neurogenesis as a baby, a toddler and an adolescent,” Lazarov said. “These are all signs that these hippocampi are growing new neurons.”
The results showed that hippocampal neurogenesis, or the formation of new neurons in the hippocampus, does indeed occur in healthy adults. Furthermore, the supers actively produced more new neurons than their counterparts – their distinct ‘resilience signature’.
“The elderly had twice as much neurogenesis as the other healthy elderly,” Lazarov said. “Something in their brain allows them to maintain a superior memory. I believe that hippocampal neurogenesis is the secret ingredient, and the data supports it.”
Brain samples from people with preclinical cognitive decline — the earliest stage of cognitive decline, before symptoms begin to appear — showed little neurogenesis. Those diagnosed with Alzheimer’s disease created almost no new neurons.
In addition, the researchers observed that the new neurons had different epigenetic signatures—or blueprints for responding to environmental change—depending on the cognitive health of the brain.
“Modern medicine has revolutionized health care so that life expectancy is longer now than ever before,” said co-lead author Dr. Jalees Rehman, the Benjamin J. Goldberg Professor and Chair of the Department of Biochemistry and Molecular Genetics at UIC. “We need to ensure that this overall increased life expectancy is accompanied by a high quality of life, including cognitive health.”
Rehman said understanding the full molecular picture of neurogenesis and its epigenetic signature can inform targeted therapies to preserve memory and cognitive function in older adults. Next, this team will examine environmental and lifestyle factors—such as diet, exercise, and inflammation—that may work in tandem with neurogenesis to influence aging.
“What is exciting for the public is that this study shows that the aging brain is not fixed or doomed to decline,” said Ahmed Disouky, the study’s first author. “Understanding how some people naturally preserve neurogenesis opens the door to strategies that could help more adults maintain memory and cognitive health as they age.”
Additional UIC collaborators include Mark Sanborn, KR 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 Trust Research Initiative, the Karen Toffler-Gefeny-Charitue. The study was supported by National Institute on Aging awards AG033570, AG033570-S2, AG076940, AGO79002, AG060238, AG061628, and AG091545.
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