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As many brains age, they accumulate faulty proteins that lead to cell death and cognitive decline. But some individuals remain remarkably sharp, exhibiting the same mental acuity at 80 as they did at 50. A new study published Wednesday in the journal Nature offers a potential explanation for this discrepancy, addressing a central question in neuroscience: whether the human brain can generate new neurons throughout adulthood, a process known as neurogenesis.
Researchers found that so-called “super-agers” – individuals aged 80 and older with memory capacity comparable to someone 30 years younger – had approximately twice the number of new neurons as older adults with typical age-related memory decline and 2.5 times more than individuals with Alzheimer’s disease. The investigation focused on the hippocampus, a brain region crucial for learning and memory, and believed to be a primary source of new neurons. This research adds to the growing body of evidence suggesting that brain plasticity extends well into advanced age.
“This paper shows biological proof that the aging brain is plastic,” even at 80 years and beyond, said Tamar Gefen, associate professor of psychiatry and behavioral sciences at Northwestern University’s Feinberg School of Medicine, who contributed to the research. The findings could have significant implications for understanding and potentially mitigating age-related cognitive decline.
To investigate neurogenesis in older adults, the scientists initially sought to identify markers of the process in post-mortem brain tissue from young adults, aged 20 to 40, who had normal cognitive function. They identified genetic markers for three key cell types: neural stem cells, neuroblasts, and immature neurons. “It’s almost as if the neural stem cells are babies, the neuroblasts are like teenagers, and the immature neurons are almost adults,” explained Orly Lazarov, professor of neuroscience at the University of Illinois Chicago College of Medicine, who led the study.
The presence of all three cell types suggests that stem cells are active and dividing in the brain, and that these new cells are maturing into adult neurons. The researchers then searched for these same three cell types in the brains of four groups of older adults: those with normal cognition, those with mild cognitive impairment, those with Alzheimer’s disease, and the “super-agers” who had donated their brains for research after their death. Each group showed evidence of the three cell types, but the quantities varied considerably and appeared to correlate with the individuals’ cognitive abilities at the time of death.
Super-agers had significantly 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 that researchers believe contribute to their resilience against aging. “Super-aging happens not just because there are more of these young cells, but because there’s a type of genetic programming” that allows for their preservation, Dr. Gefen stated.
Dr. Bryan Strange, a professor of clinical neuroscience at the Polytechnic University of Madrid who studies a different cohort of older individuals, suggested that neurogenesis could help explain other unique aspects of super-agers’ brains, including the fact that their hippocampi are often larger than those of typical older adults. Nature
However, he noted that older adults have other brain differences, such as increased volume in areas that don’t experience neurogenesis and greater connectivity between brain regions, that cannot be explained by the new findings. These observations highlight the complexity of brain aging and the need for further research.
The research also revealed intriguing insights regarding individuals with Alzheimer’s disease. They actually had more neural stem cells than the other older adult groups, but significantly fewer neuroblasts and immature neurons. “If neurogenesis is normal, stem cells are gradually lost,” explained 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. One interpretation of the new finding is that in Alzheimer’s, neurogenesis is disrupted, and the stem cells become stalled, preventing them from progressing to the next stage of development, thus preserving the pool of stem cells.
“If that’s true, it really opens a new direction for the field” to potentially treat Alzheimer’s by reactivating these dormant stem cells, Dr. Song said. This potential therapeutic avenue is generating considerable excitement within the neuroscience community.
Not all researchers are fully convinced by the study’s findings. Shawn Sorrells, associate professor of neuroscience at the University of Pittsburgh, who has also investigated neurogenesis, acknowledged that the scientists’ goal of mapping “how the hippocampus changes with aging and how it changes differently in people who age differently is incredibly 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. He added that he would like to notice the findings validated using other techniques.
Experts generally agree that infants and young children are capable of generating new neurons in the brain, as are several animal species. However, there remains considerable debate about whether adult humans retain the same capacity. Numerous studies offer evidence on both sides, and the results are often influenced by the methods employed by researchers. The question of adult human neurogenesis remains a complex and actively investigated area of scientific inquiry.
This latest study is unlikely to settle the debate definitively, but it does provide scientists with new clues to explore. Dr. Lazarov is now working to understand how the special immature neurons of super-agers relate to the group’s superior memory, and whether it might be possible to capture some of that activity in a drug to help others stay sharper for longer.
The findings underscore the importance of continued research into the biological mechanisms underlying healthy brain aging. Whereas lifestyle factors like diet and exercise are known to contribute to cognitive health, understanding the fundamental processes within the brain itself is crucial for developing effective interventions to prevent and treat age-related cognitive decline.
Disclaimer: This article provides informational content about health and medical research and is not intended to be a substitute for professional medical advice. Always consult with a qualified healthcare provider for diagnosis and treatment of any medical condition.
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