Research from the University of Illinois College of Medicine Chicago has uncovered significant genetic advantages in older adults known as “super-agers.” These individuals, aged 80 and older, demonstrate cognitive abilities comparable to those of younger adults thanks to their ability to generate twice as many new neurons in the hippocampus, a vital region for learning and memory. The findings, published on March 15, 2024, in the journal Nature, highlight the unique biological traits that distinguish super-agers from their peers.
Study co-author Orly Lazarov, director of the Alzheimer’s Disease and Related Dementia Training Program at UIC, explained that this enhanced neurogenesis provides super-agers with a molecular capability that supports higher cognitive performance. “Neurogenesis is one of the most profound forms of plasticity in the brain,” she noted, emphasizing the adaptability of these individuals’ brains.
The term “super-ager” was coined by Dr. M. Marsel Mesulam, founder of the Mesulam Institute for Cognitive Neurology and Alzheimer’s Disease at the Northwestern University Feinberg School of Medicine. It refers to individuals who maintain memory capacities akin to those of people two to three decades younger, as determined by delayed word recall tests.
In their study, Lazarov and her team analyzed the brain samples of 38 deceased adults across five groups: healthy adults aged 40 and under, healthy older adults, individuals in early stages of cognitive decline, those diagnosed with Alzheimer’s disease, and super-agers. The six super-ager brains were donated by participants in Northwestern’s SuperAging Program, which recently celebrated its 25th anniversary.
The research revealed that super-agers possess twice as many new, or “immature,” neurons compared to healthy older adults, and two and a half times more than those with Alzheimer’s disease. This challenges the long-held belief that mammals are born with a fixed number of neurons. Since the mid-20th century, scientists have recognized that adult neurogenesis occurs in certain brain regions, including the dentate gyrus of the hippocampus, although understanding of this process in humans has been limited.
Lazarov stated, “We have established the presence of this process and its roles in learning and memory in rodents and in primates. Whether the human brain functions in a similar way is a very critical question for us.” The study suggests that while age and cognitive status influence neurogenesis, super-agers exhibit a distinct “resilience signature” in their brains that enables them to cope better with aging and maintain cognitive function.
In addition to neurogenesis, the research identified changes in astrocytes and CA1 neurons, which play a role in regulating memory and cognition in the aging hippocampus. Despite these promising findings, the authors acknowledged limitations within the study, including its small sample size and the variability typical among human brain specimens.
This research marks a significant step in understanding the genetic differences between super-agers and typical older adults. According to Tamar Gefen, co-director of the SuperAging Program, the discovery that super-agers maintain immature neurons capable of rewiring themselves is groundbreaking. “There is no question that their hippocampi are completely different than other human beings,” she stated.
The SuperAging Program has uncovered other intriguing traits associated with super-agers, such as extroversion and a higher number of von Economo neurons, which are linked to social behavior. Gefen highlighted the importance of socialization for healthy aging while cautioning against the detrimental effects of isolation. Super-agers often exhibit adaptability and low levels of neuroticism, characteristics that contribute to their cognitive resilience.
Research indicates that while healthy brains typically shrink with age, super-agers experience this process at a slower rate. A 2017 study published in the Journal of the American Medical Association found that their brains exhibit less shrinkage compared to peers. Furthermore, a 2021 study in Cerebral Cortex revealed that super-agers show resistance to neurofibrillary tangles, abnormal protein accumulations associated with Alzheimer’s disease.
The immune system’s role in brain health has also been explored. In a 2019 study published in Frontiers in Aging Neuroscience, Gefen’s team discovered that super-agers have fewer activated microglia, the brain’s immune cells, compared to individuals with dementia, suggesting a more youthful immune response.
For those who do not classify as super-agers, maintaining cognitive health is still achievable. Dr. Jennifer Pauldurai, medical director of the Inova Brain Health and Memory Disorders Program, emphasized the importance of prioritizing cognitive well-being throughout life. “Now’s the time to prioritize cognitive well-being, long before natural decline or dementia sets in,” she advised.
Pauldurai likened the brain to a malleable substance, stating that while genetics may play a role, active engagement in cognitive and physical activities can foster neural growth. “If we are not actively using our brains, they will harden and become difficult to work with,” she explained.
Sel Yackley, an 86-year-old participant in the SuperAging Program, shared her perspective on cognitive resilience. “I guess we’re lucky,” she said, referring to her experience of continuously forming new neurons. Yackley remains active through various hobbies and emphasizes the importance of staying engaged, even as she faces typical cognitive challenges of aging. “Don’t worry about the years. Just stay active, mentally and physically,” she advised.
As the population ages, understanding the mechanisms behind super-aging could provide valuable insights into enhancing cognitive resilience across different demographics. The findings from this research not only highlight the unique advantages of super-agers but also offer hope and guidance for maintaining brain health for all.
