The human brain changes with age, often accumulating damaged proteins that contribute to cell death and cognitive decline. But for some, the brain remains remarkably sharp well into their 80s and beyond, exhibiting memory and cognitive function comparable to individuals decades younger. Novel research published this week in the journal Nature offers a potential explanation for this disparity, focusing on the brain’s ability to generate new neurons throughout life – a process known as neurogenesis – and identifying key differences in the brains of “super-agers.”
The study found that individuals aged 80 and older with exceptional memory capabilities—essentially, the cognitive function of someone 30 years younger—possessed roughly twice the number of new neurons compared to older adults with typical age-related memory decline and 2.5 times more than those with Alzheimer’s disease. Researchers focused on the hippocampus, a brain region crucial for learning and memory, and considered a primary source of these new neurons. This finding suggests that the aging brain retains a surprising degree of plasticity, even at advanced ages.
“This paper shows biological proof that the aging brain is plastic,” even into a person’s 80s, said Tamar Gefen, associate professor of psychiatry and behavioral sciences at Northwestern University’s Feinberg School of Medicine, who contributed to the research. The work builds on growing interest in understanding why some individuals are protected from the cognitive effects of aging, and could open new avenues for interventions to promote healthy brain aging.
Mapping the Cellular Landscape of Super-Agers
To investigate neurogenesis in older adults, the scientists first sought to identify genetic markers of the process in post-mortem brain tissue from young adults, aged 20 to 40, who had normal cognitive function at the time of their death. They pinpointed genetic signatures for three key cell types: neural stem cells, neuroblasts, and immature neurons. According to Orly Lazarov, professor of neuroscience at the University of Illinois Chicago, who led the research, “It’s almost as if the neural stem cells are babies, the neuroblasts are kind of teenagers, and the immature neurons are almost adults.” The presence of all three cell types indicated active stem cell activity and the maturation of new cells into functional neurons.
The team then examined brain tissue from four groups of older adults: those with normal cognition, those with mild cognitive impairment, individuals with Alzheimer’s disease, and “super-agers” – those over 80 who demonstrated memory performance on par with much younger individuals. All groups showed evidence of the three cell types, but the quantities varied significantly and appeared correlated with cognitive function. Super-agers had substantially more immature neurons in the hippocampus, not only compared to other older adults, but also to the young adults. These immature neurons also exhibited unique genetic and epigenetic characteristics, suggesting a resilience to the aging process.
Alzheimer’s Disease: A Blocked Pathway?
Interestingly, the research also shed light on the cellular differences in the brains of individuals with Alzheimer’s disease. Whereas they had more neural stem cells than other older adults, they had significantly fewer neuroblasts and immature neurons. Hongjun Song, professor of neuroscience at the University of Pennsylvania’s Perelman School of Medicine, who researches neurogenesis but was not involved in the study, explained that “If neurogenesis is normal, the stem cells are gradually lost.” He suggests the new findings indicate that in Alzheimer’s, neurogenesis is disrupted, and the stem cells become stalled, unable to progress to the next stage of development, preserving the pool of stem cells but failing to create new functional neurons.
“If that’s true, it really opens a new direction for the field” to potentially treat Alzheimer’s by reactivating these latent stem cells, Dr. Song added.
Beyond Neurogenesis: A Complex Picture
While the findings are promising, researchers caution that neurogenesis is likely only one piece of the puzzle. Bryan Strange, professor of clinical neuroscience at the Polytechnic University of Madrid, who studies aging, noted that neurogenesis may assist explain other unique aspects of super-agers’ brains, including a larger hippocampus compared to typical older adults. However, he also pointed out that older adults exhibit other brain differences – such as increased volume in areas not associated with neurogenesis and greater connectivity between brain regions – that aren’t fully explained by the new research.
Not all researchers are fully convinced by the findings. Shawn Sorrells, associate professor of neuroscience at the University of Pittsburgh, who has also investigated neurogenesis, acknowledged that the study’s goal of mapping “how the hippocampus changes with aging and how it changes differently in people who age differently” is “extremely interesting and important.” However, Dr. Sorrells expressed concern that the study may suffer from some of the same methodological limitations and assumptions as other neurogenesis research, and called for validation of the findings using additional techniques.
The Ongoing Debate About Adult Neurogenesis
The question of whether adult human brains can generate new neurons remains a subject of ongoing debate. While neurogenesis is well-established in infants and children, and in several animal species, its extent in adult humans is still unclear. Numerous studies have presented evidence on both sides, with results often influenced by the methods used by researchers. The study by Lazarov and colleagues adds to this body of evidence, providing further support for the possibility of continued neurogenesis in the aging human brain.
Dr. Lazarov’s team is now working to understand how the unique immature neurons of super-agers relate to their superior memory performance, and whether it might be possible to harness some of that activity in a drug to help others maintain cognitive function for longer. The research represents a significant step forward in understanding the biological basis of healthy brain aging and could pave the way for new strategies to prevent or delay cognitive decline.
Disclaimer: This article provides information for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
Stay informed about the latest research on brain health and aging. You can uncover more information from the National Institute on Aging.
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