The remarkable brains of ‘SuperAgers’ hold clues about how we age

A look inside the brains of extraordinarily sharp elderly people reveals clues about their unusual abilities. Deep in these exceptional brains were signs of what some scientists believe to be newborn nerve cells, born well into old age.

The results, published February 25 in Nature, add datapoints to the scientific debate about whether adults can make new neurons, a process called neurogenesis, and if they can, what those neurons are good for.

Whether that debate is now settled depends on who you ask — as not everyone agrees that the reported signs are from dividing neurons. 

Neuroscientist Orly Lazarov of the University of Illinois Chicago and colleagues set out to investigate how different brains age, and what sorts of changes might keep some people sharp for decades. Their study focused on brain samples taken after death, giving the researchers access to brain tissue that would otherwise be unreachable. The tissue came from five groups of six to 10 people each: young, healthy adults; old, healthy adults; old adults with early signs of dementia; old adults with Alzheimer’s disease; and “SuperAgers,” adults at least 80 years old with the memory power of a person 30 years younger.

Studying a collection of brains with such range in age and cognitive status is “unbelievable, unprecedentedly exciting stuff,” says neuroscientist Shawn Sorrells of the University of Pittsburgh, who wasn’t involved in the study.

For this study, the researchers zeroed in on the seahorse-shaped hippocampus; located on each side of the brain, hippocampi are crucial for memory formation and other tasks such as navigating. Specifically, they looked at particular genetic signatures — collections of genes that were either active or inactive — inside the nuclei of brain cells taken from this region. These signatures belong to cells involved in neurogenesis, including newly created neurons and their parents, the scientists reasoned.

The signatures turned up in all the groups to varying degrees. But there were some key differences among them.

SuperAgers, the analysis suggests, had about 2.5 times the number of these immature cells compared with people who have Alzheimer’s disease. Other comparisons yielded less clear outcomes, though there were hints of more new neurons in SuperAgers than in young adults, old adults and old adults with early signs of dementia. That youthful abundance of neurogenesis could be behind SuperAgers’ mental strength, the researchers suspect.

Because of the small numbers of brains in the study, it’s hard to say how solid this trend might be, Lazarov says. “We have to be a little careful with that.” The key insight, she says, is that the genetic signatures are distinct in SuperAgers.

Not everyone agrees that neurogenesis is happening, much less providing benefits. “The assumption that these cells are truly dividing is a major leap unsupported by their data,” Sorrells says. He suspects that the genetic analysis method used in the new study could have erroneously classified cells as new neurons.

Still, Lazarov says, “the best I can say is that given the tools that we have right now, this is the best evidence we have.”

The results don’t mean that SuperAgers aren’t aging. “We could clearly see that their profile was very different than the young adults,” Lazarov says. But “they had a unique signature, a unique profile of genes that allowed them to cope with the aging process.” Neurogenesis, she adds, may be one piece of that coping process.

Exploring brain changes that come with aging is important, Sorrells says. “That’s super interesting, super exciting — a fantastic question. But it’s all predicated on this notion that they’re identifying the cells correctly.”

The debate, which hinges on what counts as proof when it comes to unambiguously detecting newborn neurons, speaks to the complexity of the human brain, Sorrells says. “The brain has a lot of mysteries that are yet to be revealed.”