Genetic Advantages of Aging Cognitively Sharp

New research indicates that older adults who maintain their cognitive abilities as they age may possess a genetic edge compared to others.

A study from the University of Illinois College of Medicine in Chicago discovered that individuals labeled as super-agers produce twice the number of new neurons in the hippocampus—a brain area crucial for learning and memory—than their peers. The findings were published in the journal Nature.

Orly Lazarov, a co-author of the study and director of UIC’s Alzheimer’s Disease and Related Dementia Training Program, explains, “This discovery suggests that super-agers possess a molecular ability that allows for superior cognitive performance, which includes increased neurogenesis.” She noted that neurogenesis is one of the more significant forms of brain plasticity.

Essentially, super-agers’ brains display greater adaptability.

A super-ager, as defined by Dr. M. Marsel Mesulam, founder of the Mesulam Institute for Cognitive Neurology and Alzheimer’s Disease at Northwestern University Feinberg School of Medicine, is someone over 80 who exhibits memory capacities akin to people two to three decades younger, evaluated via delayed word recall tests.

In this study, Lazarov and her team examined 38 brains from five groups of deceased adults: healthy adults aged 40 and under, healthy older adults, individuals in early cognitive decline, those diagnosed with Alzheimer’s, and super-agers. The six super-ager brains came from Northwestern’s SuperAging Program, which celebrated its 25th anniversary last year.

The researchers analyzed neurons at various developmental stages within the brain samples. They observed that super-agers had twice as many new, or “immature,” neurons as healthy older adults. Notably, compared to individuals with Alzheimer’s, super-agers exhibited two and a half times more immature neurons.

Up until the mid-20th century, it was generally believed that mammals were born with a set number of neurons. It was only in the 1960s and ’70s that scientists recognized adult neurogenesis in rodents and primates.

While it’s been acknowledged in humans—specifically within the dentate gyrus of the hippocampus—the evidence has been inconsistent, and the underlying mechanisms remain not well understood.

“We’ve established that this phenomenon exists and its role in learning and memory in rodents and primates,” shared Lazarov. “The crucial question for us is whether the human brain operates similarly.”

Her research implies that human brains can not only develop new neurons but that this ability is influenced by age and cognitive state.

According to Lazarov, super-agers’ brains display a “resilience signature.” “They manage aging effectively and maintain strong cognitive performance,” she highlighted.

The study also found that alterations in two types of cells—astrocytes and CA1 neurons—play a role in memory and cognitive function in an aging hippocampus.

However, the authors acknowledged some limitations to the study, including a small sample size and the usual variability among human brain samples.

Insights from Super-agers Over 25 Years

This research marks a significant finding regarding the genetic distinctions between super-agers and typical older adults, according to the Northwestern SuperAging Program.

“These individuals, well into their 80s and 90s, are still producing immature neurons that are actively reorganizing themselves,” stated Tamar Gefen, co-director of the program and a co-author of the study. “Their hippocampi are fundamentally different from those of others, period.”

The program has revealed various characteristics of exceptionally healthy older brains—from personality traits to neurological differences. For instance, Gefen noted that super-agers often view themselves as extroverts. They also tend to have more von Economo neurons, which are associated with social behaviors.

“We’ve repeatedly heard how vital social interaction is for healthy aging—while isolation can be quite harmful,” she remarked.

Super-agers are also flexible and open to new experiences, often exhibiting low levels of neuroticism, according to Gefen.

While it’s natural for healthy human brains to shrink with age—especially in conditions like Alzheimer’s—research published in 2017 in the Journal of the American Medical Association indicates that super-agers’ brains tend to shrink at a slower rate compared to their counterparts.

In 2021, Gefen and her team published findings in the journal Cerebral Cortex, suggesting that super-agers exhibit resistance to neurofibrillary tangles—abnormal protein aggregations associated with Alzheimer’s disease.

Concerning immunity, the brains of super-agers raise as many questions as they answer. Microglia, the immune cells present in the brain, become activated in individuals with neurodegenerative disorders. A 2019 study published in the journal Frontiers in Aging Neuroscience revealed that super-agers had not only fewer activated microglia than those with dementia but also a quantity comparable to individuals 30 to 40 years younger.

Staying Sharp Beyond Super-aging

The findings from this study suggest that super-agers may have struck genetic gold.

“I guess we’re lucky,” said Sel Yackley, a participant in the Northwestern SuperAging Program. “We’re generating new neurons.”

The 86-year-old from Chicago playfully noted that she’s keeping up with her “super-ager duties,” which include knitting, exercising, making jewelry, singing in a choir, and checking tasks off her to-do list. Although her in-person social interactions have diminished, she focuses on staying connected with friends via calls, emails, and Zoom.

While Yackley takes pride in being a super-ager, she acknowledges the cognitive challenges aging brings.

“There are some memories that feel fresh, like they happened yesterday, but then there are things I forget,” she reflected.

However, Dr. Jennifer Pauldurai, medical director of the Inova Brain Health and Memory Disorders Program in northern Virginia, emphasizes that even non-super-agers can take significant steps to enhance brain health throughout their lives. It’s crucial to prioritize cognitive wellness long before age-related decline or dementia emerge.

“I find the idea of super-aging inspiring because it empowers us. Dementia and Alzheimer’s rates are on the rise,” remarked Pauldurai, who was not part of the study. “If there’s a way to make the aging process less severe, we should definitely explore it.”

This recent research highlights the brain’s capacity for change, with Pauldurai likening its potential to a lump of clay. Even if some are born with superior “clay,” it can be shaped and developed over a lifetime to enhance neural connections.

However, a neglected clay lump, neglected over time, hardens and becomes increasingly difficult to work with.

“This analogy parallels how our brains behave if we aren’t actively engaging them—if we neglect cognitive fitness and physical activity throughout our lives,” she explained.

Maintaining overall health is vital for a flexible brain, Pauldurai added, as factors like poorly managed chronic illnesses or untreated emotional trauma can hinder neuron generation.

“Discussing preventive healthcare and brain wellness before significant damage occurs is essential,” she expressed. “I would much rather focus on this than admit the lack of a cure for Alzheimer’s disease.”

Yackley, a former journalist, believes her cognitive resilience traces back to her career’s demands.

“I had a curious mind,” she recalled. “I followed many stories and interviewed numerous people—perhaps that contributed to my neurons.”

Her advice for those who aren’t super-agers? Stay busy and actively engaged.

“Don’t fret about getting older,” Yackley advised. “Just keep moving—both mentally and physically.”