March 17th, 2026

Written by Andrew Nguyen

Growing numbers are growing old

The aging population is rapidly growing worldwide but there is still so much unknown about the biology of aging. The World Health Organization (WHO) reports that 1 in 6 individuals will be over the age of 60 by 2030 and that between 2020 and 2050, the number of people 80+ years old is expected to triple¹. This growing population of older individuals is at an increased risk for a number of age-related health issues, such as memory loss and cognitive decline, that are still poorly understood. During normal aging, there is typically memory and cognitive decline (i.e. language, spatial navigation, information processing) later in life. Occasionally forgetting a set of keys or a phone may be more common in older adults. In some adults, however, there is more severe memory loss that may look like being lost in a familiar place or forgetting a familiar person. Severe forms of memory loss, cognitive decline, and dementia resulting from neurological diseases, like Alzheimer’s Disease, are referred to as pathological aging, and are also more likely to start appearing later in life. By studying how the brain ages under typical conditions, neuroscientists can gain insight into how neurological diseases, like Alzheimer’s, lead to deficits in memory and cognition. Both of these “normal” and “pathological” age-related memory and cognitive impairments present a dire need for biomedical research to investigate the biology of what happens as we age. 

While many older people experience memory and cognitive impairments with age, some elderly individuals, so called SuperAgers, remain cognitively exemplary with a sharp mind comparable to that of a youthful 20-30 year old. Neuroscientists can learn a lot from studying SuperAgers to better understand what causes age-related memory loss. If neuroscientists can understand how SuperAgers’ brains age to protect them against cognitive decline, they may be able to harness that knowledge to build treatments and therapies that support healthy aging.

Studying resilience in SuperAgers 

SuperAgers have an incredible power of “super-memory”, but how can neuroscientists learn from them? First, SuperAgers have to be found. In order to be classified as a SuperAger, individuals go through a battery of cognitive tests to determine how strong their memory is for long-term personal memories, referred to as episodic memories. By studying how SuperAgers can retain episodic memories so well, scientists can unravel how memory declines during aging and identify new interventions to reduce cognitive decline in older adults. Neuroscientists worldwide have developed small but mighty programs, like the SuperAger Program at the Northwestern Alzheimer’s Disease Research Center, to study SuperAgers and understand what is happening in their brains that makes them so resilient to memory loss. 

Compared to their peers, the brains of SuperAgers retain larger, healthier neurons in an area of the brain typically associated with spatial memory formation and is one of the first areas that becomes damaged in Alzheimer’s Disease, called the entorhinal cortex². Neurons in the entorhinal cortex of SuperAgers were not only larger than other healthy adults their age, but were even comparable to the average 20-30 year old (similar to the “age” of their memory performance!). These findings demonstrate meaningful differences in the brains of SuperAgers compared to the average older adult that is likely to experience age-related cognitive decline; however, the million dollar question is how differences between SuperAgers and their peers actually result in functional differences in memory. 

New tools to understand new neurons

Seeing larger neurons helps neuroscientists confirm that SuperAgers may have measurable differences in their brains, but how their brains function differently to promote resilience to age-related memory loss is still an important unknown. For decades, neuroscientists debated whether the adult brain can produce new neurons, a process called neurogenesis. Thanks to new techniques developed in the last century, the field is finally coming to an agreement that neurogenesis does occur in the adult brain and there’s exciting evidence that neurogenesis may play an important role in memory and age-related memory decline 

Using cutting edge research techniques, researchers have shown that neurogenesis in a brain area important for learning and memory, called the hippocampus, occurs in adult rodents. In the rodents studied, hippocampal neurogenesis supported memory formation by recruiting new neurons to active memory circuits³. Further, the rate of neurogenesis in the hippocampus appears to slow with age, getting even slower in animal models of Alzheimer’s Disease⁴. These findings provide a potential role for hippocampal neurogenesis in supporting healthy memory and identify a reduced ability to generate new neurons as a possible cause of memory loss. 

Observing neurogenesis in a rodent brain is only possible because of new and exciting technology that allows researchers to experimentally inject molecular tracers into the brain to look at newborn neurons during aging. Determining whether what’s been found in rodent brains is also true of the human brain has been challenging due to experimental limitations of labeling newborn neurons and only having access to brain tissue post-mortem. However, new techniques developed to understand the diversity of neuron types have confirmed the existence of immature neurons in the adult human brain, suggesting that neurogenesis also takes place in humans. Immature neurons have not only been found in the adult human brain, but fewer of them are found in people diagnosed with Alzheimer’s Disease who have pathological memory loss and cognitive decline⁵. Combined with findings from rodent studies, these findings suggest that the ability to produce new neurons may be essential for supporting healthy memory formation. This led a recent group of researchers to wonder whether neurogenesis might also explain why SuperAgers remain resilient to age-related memory loss.

New insights into cognitive aging

To determine whether hippocampal neurogenesis plays a role in SuperAgers’ “super memory”, neuroscientists used a technique that determines which genes a neuron uses to go about its daily functions, called multiomic sequencing, to identify neurons at different stages of maturity. This works because younger neurons use different genes than older, mature neurons, so the profile of genes being used by a neuron gives insight into its age⁶. The researchers compared the hippocampus of human brain tissue across five groups: young adults with healthy cognition, older adults with cognition typical of their age, older adults with early signs of cognitive decline, older adults with diagnosed Alzheimer’s disease, and SuperAgers. The goal of the study was to determine how SuperAgers’ super memory are different at a molecular level and if this could be explained by differences in neurogenesis.

By comparing brain tissues from different groups of people with varying memory and cognitive abilities, the researchers were able to identify several factors that may explain why SuperAgers have extraordinary memory abilities. The first major finding from the multiomic sequencing was that the researchers were able to successfully identify different classes of immature neurons in the hippocampus and molecular signatures of genes that are involved, confirming human neurogenesis at a deeper level than ever before. The second major finding was that SuperAger brains had many more immature neurons than the other groups, suggesting that neurogenesis may be a key driver in supporting their super memory. The scientists also identified unique gene “resilience signatures” from SuperAger hippocampal samples compared to the other groups that suggest that communication between neurons was more efficient. Going even further, the researchers looked at the gene lists differing the most between SuperAgers and their peers with typical cognition for their age. Using this approach they identified two cell types in particular, astrocytes and neurons of the hippocampus, that had the most profound genetic differences. The genetic differences in hippocampal astrocytes might play a meaningful role in supporting hippocampal neurogenesis and promoting super memory in SuperAgers, that may be interesting for future work. These results point to neurogenesis being a key player in the extraordinary memory of SuperAgers, demonstrating specific molecular resilience signatures of how their brains are strengthened against age-related memory loss⁶. This understanding of how neurogenesis supports SuperAgers’ super memory gives neuroscientists an idea of how the brain and cognition should be changing with age normally and what may be going wrong in pathological states. 

By studying different types of aging populations, ranging from disease-releated cognitive decline to extraordinary cognition, this research highlights new molecular and cellular clues into how the human brain changes during aging. Understanding that SuperAgers have a greater ability to generate new neurons may lead to further research to see if boosting neurogenesis during normal or pathological age-related memory loss also boosts memory. While this research is exciting and suggests a relationship between neurogenesis, cognition and SuperAgers, it’s important to note that these differences were shown in a relatively small sample size and it will be important to confirm them across a larger population before concluding anything concrete. Nonetheless, these findings provide an important foundation for understanding how the brain changes with age and could lead to a new line of research into neurogenesis as a therapeutic target for age-related cognitive decline. Interestingly, the link between neurogenesis and healthy aging might also explain why exercise has so many proven benefits for cognition and aging, because other research has shown that exercise can promote adult neurogenesis in rodents⁷. Future research might consider whether SuperAgers engaged in particular types of levels of exercise throughout their lives or if exercise can cause the brain of a typical ager to look more like that of a SuperAger. Wherever future research may lead, understanding SuperAgers paves the way for a deeper understanding into how we can all age with extraordinary cognition.

References

1. World Health Organization https://www.who.int/news-room/fact-sheets/detail/ageing-and-health
2. Nassif C, Kawles A, Ayala I, Minogue G, Gill NP, Shepard RA, Zouridakis A, Keszycki R, Zhang H, Mao Q, Flanagan ME, Bigio EH, Mesulam MM, Rogalski E, Geula C, Gefen T. Integrity of Neuronal Size in the Entorhinal Cortex Is a Biological Substrate of Exceptional Cognitive Aging. J Neurosci. 2022 Nov 9;42(45):8587-8594. doi: 10.1523/JNEUROSCI.0679-22.2022. Epub 2022 Sep 30. PMID: 36180225; PMCID: PMC9665923.
3. Marin-Burgin, A., Mongiat, L. A., Pardi, M. B. & Schinder, A. F. Unique processing during a period of high excitation/inhibition balance in adult-born neurons. Science 335, 1238–1242 (2012).
4. Demars, M., Hu, Y. S., Gadadhar, A. & Lazarov, O. Impaired neurogenesis is an early event in the etiology of familial Alzheimer’s disease in transgenic mice. J. Neurosci. Res. 88, 2103–2117 (2010).
5. Zhou, Y. et al. Molecular landscapes of human hippocampal immature neurons across lifespan. Nature 607, 527–533 (2022).
6. Disouky, A., Sanborn, M.A., Sabitha, K.R. et al. Human hippocampal neurogenesis in adulthood, ageing and Alzheimer’s disease. Nature (2026). https://doi.org/10.1038/s41586-026-10169-4
7. Liu PZ, Nusslock R. Exercise-Mediated Neurogenesis in the Hippocampus via BDNF. Front Neurosci. 2018 Feb 7;12:52. doi: 10.3389/fnins.2018.00052. PMID: 29467613; PMCID: PMC5808288.

Cover photo by Clément Falize on Unsplash.