Many brains deteriorate with age, accumulating faulty proteins that lead to cell death and memory and cognitive decline. However, other brains remain remarkably intact, exhibiting the same mental sharpness at 80 as they did at 50.
A study published in the journal Nature offers a potential new explanation for this discrepancy and addresses one of the most hotly debated topics in neuroscience: whether human brains can generate new neurons in adulthood, a phenomenon called neurogenesis.
The study found that so-called “SuperAgers” – individuals aged 80 or older with the memory capacity of someone 30 years younger – had roughly twice as many new neurons as older adults with typical memory for their age and 2.5 times as many as people with Alzheimer’s disease. The research focused on a brain region called the hippocampus, which is crucial for learning and memory, and is believed to be a primary source of new neurons.
“This paper shows biological proof that the aging brain is plastic,” even as the individual reaches their 80s, said Tamar Gefen, an associate professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine, who contributed to the research.
To investigate neurogenesis in older adults, scientists first attempted to detect signs of it in post-mortem brains from young adults, aged 20 to 40, who died with normal cognition. They identified genetic markers for three key cell types: neural stem cells, neuroblasts, and immature neurons.
“It’s almost as if the neuronal 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 College of Medicine, who led the research. The presence of all three types could suggest that the stem cells are active and dividing in the brain, and that those new stem cells are maturing into adult neurons.
The scientists then looked for these same three cell types in the brains of four groups of older adults: people with normal cognition, people with mild cognitive impairment, people with Alzheimer’s disease, and exceptionally aged individuals – those “SuperAgers” – who had donated their brains for study after their death. Each group showed signs of all three cell types, but the quantities differed considerably between them and appeared to correlate with the individuals’ cognition at the time of death.
SuperAgers had significantly more immature neurons in the hippocampus, not only compared to other older adults, but also compared to the young adults. These immature neurons also exhibited unique genetic and epigenetic characteristics that the researchers believe conferred resilience to aging.
“SuperAging happens not only because You’ll see more of these young cells, but because there’s a type of genetic programming” that allows for their preservation, Dr. Gefen said.
Bryan Strange, a professor of clinical neuroscience at the Polytechnic University of Madrid who studies a different group of older people, suggested that neurogenesis could help explain other unique aspects of SuperAgers’ brains, including the fact that the hippocampus is often much larger than in typical older adults.
However, he pointed out that older individuals have other brain differences, such as greater volume in areas that do not experience neurogenesis and increased connectivity between brain regions, that cannot be explained by the new findings.
The research also revealed something intriguing about individuals with Alzheimer’s disease. They, in fact, had more neuronal stem cells than the other older adults, but significantly fewer neuroblasts and immature neurons.
“If neurogenesis is normal, the stem cells are gradually lost,” said Hongjun Song, a professor of neuroscience at the University of Pennsylvania Perelman School of Medicine, who researches neurogenesis but did not participate in the study. One interpretation of the new finding is that, in Alzheimer’s disease, 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’s really opened a new direction for the field” to potentially treat Alzheimer’s by reactivating the latent stem cells, Dr. Song said.
Not everyone is convinced by the new findings. Shawn Sorrells, an associate professor of neuroscience at the University of Pittsburgh, who has also researched neurogenesis, said 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 suffers from some of the same methodological shortcomings and assumptions as other research on neurogenesis. He added that he would like to see the findings validated by other techniques.
Experts agree that infants and young children are capable of generating new neurons in the brain, as are several species of adult animals. However, many believe it remains unclear whether adult humans have the same capacity. Numerous studies provide evidence on both sides, and the results are often influenced by the methods employed by the researchers.
This latest study is unlikely to settle the debate, but it does offer scientists new clues to investigate. Dr. Lazarov, for her part, is attempting to understand how the special immature neurons of SuperAgers relate to the group’s superior memory, and whether it would be possible to capture some of that activity in a drug to help others stay sharp for longer.
