The brains of some individuals remain remarkably sharp well into their 80s, exhibiting memory capabilities comparable to those 30 years younger. A study published Wednesday in the journal Nature offers a potential biological explanation for this phenomenon, focusing on the brain’s capacity to generate new neurons throughout adulthood – a process known as neurogenesis.
Researchers found that individuals classified as “super-agers” – those aged 80 or older with memory performance akin to people in their 50s – possessed roughly twice the number of new neurons in the hippocampus, a brain region critical for learning and memory, compared to older adults with typical age-related memory decline. They also had 2.5 times more new neurons than individuals diagnosed with Alzheimer’s disease.
“This paper shows biological proof that the aging brain is plastic,” even at age 80, said Tamar Gefen, an associate professor of psychiatry and behavioral sciences at Northwestern University’s Feinberg School of Medicine, who contributed to the research. The study centers on the hippocampus, believed to be a primary source of these new neurons.
To investigate neurogenesis in older adults, the scientists initially identified genetic markers for three key cell types – neural stem cells, neuroblasts, and immature neurons – in post-mortem brain tissue from young adults, aged 20 to 40, who had normal cognitive function. “It’s almost as if the neural stem cells are babies, the neuroblasts are kind of teenagers, and the immature neurons are almost adults,” explained Orly Lazarov, a professor of neuroscience at the University of Illinois Chicago, who led the investigation.
The presence of all three cell types suggested active stem cell division and the maturation of those cells into functional neurons. The team then searched for these same markers 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 deaths. All groups exhibited evidence of the three cell types, but the quantities varied significantly and correlated with the individuals’ cognitive abilities at the time of death.
Super-agers displayed a substantially higher number of 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, which researchers believe contribute to their resilience against aging. “Super-aging happens not just given that there are more of these young cells, but because there’s a kind of genetic programming” that preserves them, said Dr. Gefen.
Dr. Bryan Strange, a professor of clinical neuroscience at the Polytechnic University of Madrid who studies a separate cohort of older individuals, suggested that neurogenesis could help explain other distinctive features of super-agers’ brains, including a larger hippocampal volume compared to typical older adults. However, he noted that older adults also exhibit other brain differences, such as increased volume in areas not undergoing neurogenesis and enhanced connectivity between brain regions, which the new findings do not fully explain.
The research also yielded insights into Alzheimer’s disease. Individuals with Alzheimer’s had more neural stem cells than other older adults, but significantly fewer neuroblasts and immature neurons. Hongjun Song, a 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 suggested the new findings indicate that in Alzheimer’s, neurogenesis is disrupted, and 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.
Not all researchers are fully convinced by the findings. Shawn Sorrells, an 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 critical.” However, Dr. Sorrells expressed concern that the study may share methodological limitations and assumptions with other neurogenesis research, and called for validation of the findings using alternative techniques.
Experts agree that infants and young children are capable of generating new neurons in the brain, as are several animal species. However, whether adult humans retain this capacity remains a subject of debate. Numerous studies offer evidence on both sides, with results often influenced by the methods employed by researchers. A 2023 article in Rev Neurol highlighted the new era of neurodegenerative disease research and the importance of biomarker detection in understanding protein misfolding diseases.
Dr. Lazarov’s team is now working to understand how the unique immature neurons of super-agers relate to their superior memory and whether it might be possible to replicate that activity with a drug to help others maintain cognitive function for longer.
