The human brain naturally shrinks with age, impacting memory, which is just how life goes. However, there are some individuals known as “SuperAgers” who seem to defy this trend, retaining their memories as sharply as they were decades ago.
<p>Take, for instance, Carol Siegler from Palatine, Illinois. At 82, she triumphed at the American Crossword Puzzle Tournament for her age bracket, entering the competition “as a gag.”</p>
<p>“I've auditioned for ‘Jeopardy!’ twice and did well enough to get invited to the live auditions, but then Covid hit,” she shared in 2022 at 85.</p>
<p>Now, on her way to 90, Siegler remains vibrant, according to Tamar Gefen, an associate professor of psychiatry at Northwestern University's Mesulam Institute for Cognitive Neurology and Alzheimer’s Disease.</p>
<p>Gefen is involved in Northwestern’s SuperAging Program, currently tracking 113 SuperAgers. Over the years, around 80 of these SuperAgers have contributed their brain tissues to research, leading to some intriguing findings.</p>
<p>CNN reached out to Gefen to discuss the extensive work conducted over the decades, especially in light of a new study published in *Alzheimer’s & Dementia,* the journal of the Alzheimer’s Association.</p>
<p><em>This interview has been lightly edited for clarity.</em></p>
<p><strong>CNN: How do you define a SuperAger, and what insights have you gained about their behavior?</strong></p>
<p><strong>Tamar Gefen:</strong> Our definition at Northwestern is specific: a SuperAger must be over 80 and undergo thorough cognitive assessments. Participants are only included if their episodic memory—essentially their ability to recall personal past events—matches or exceeds that of cognitively healthy individuals in their 50s and 60s.</p>
<p>We’ve screened nearly 2,000 individuals who believed they might be SuperAgers, and less than 10% met the criteria. Over the last 25 years, we’ve studied around 300 SuperAgers, many of whom have donated their brains for research.</p>
<p>Interestingly, a common trait among SuperAgers is their sociability. They tend to value connections and remain actively involved in their communities, which is quite significant because we know social isolation is a risk factor for dementia. Thus, being socially active seems to offer some measure of protection against cognitive decline.</p>
<p>Moreover, SuperAgers often exhibit a strong sense of autonomy and independence, making decisions that reflect their desires. I believe successful aging goes beyond just being social. If someone feels trapped or restricted, particularly during vulnerable times like poor health or old age, it can impact their overall well-being.</p>
<p>Now, as for healthy habits, SuperAgers come in all varieties. Some live with heart disease or diabetes, aren’t that active physically, and their diets may not be any better than their peers.</p>
<p>In fact, one SuperAger enjoys four beers nightly and jokingly remarks, “Maybe it’s harmed me, but I'll never be sure.” He doesn’t have an identical twin for comparison, so we can't say if those drinks would have altered his lifespan significantly.</p>
<p><strong>CNN: You’ve made some compelling discoveries analyzing donor brain tissue. What have you found regarding the memory centers in SuperAgers’ brains?</strong></p>
<p><strong>Gefen:</strong> Our studies reveal that the cingulate cortex—a region tied to attention, motivation, and cognitive engagement—is thicker in SuperAgers compared to individuals in their 50s and 60s.</p>
<p>In the hippocampus, which is key for memory, we found that SuperAgers have three times fewer tau tangles in comparison to their peers. These tau formations are often associated with Alzheimer’s disease.</p>
<p>In Alzheimer’s, tau also affects key neurons related to maintaining attention in daily life; however, this does not seem to occur in SuperAgers. Thus, their cholinergic system appears to function more robustly, though we’re still unraveling precisely why that is.</p>
<p>This is fascinating because SuperAgers seem focused. They can concentrate, engage meaningfully, and retain information quite effectively—perhaps as if they were etching it into their minds with a chisel.</p>
<p>SuperAgers also have healthier, larger cells in the entorhinal cortex, a vital area for memory that connects to the hippocampus. Notably, the entorhinal cortex is among the first areas impacted by Alzheimer’s disease.</p>
<p>In another study, we examined the layers of cells within the entorhinal cortex of SuperAgers, carefully measuring neuron sizes. We observed that in layer two, crucial for relaying information, SuperAgers possess impressively large, intact neurons.</p>
<p>This finding was remarkable, as their neurons surpassed even those of much younger individuals, some in their 30s. This suggests a robust structural integrity; the foundational architecture of these neurons seems sturdier, which is interesting.</p>
<p>We're continuing to study these neurons to uncover their biochemical properties, to better understand what makes them unique and if similar characteristics are present in other neurons of SuperAgers. We also aim to investigate whether these neurons show increased vulnerability in individuals with Alzheimer's disease, and if so, what the mechanisms might be.</p>
<p><strong>CNN: What’s your insight into how a SuperAger's brain responds to injury, disease, and stress?</strong></p>
<p><strong>Gefen:</strong> We’re currently investigating the inflammatory responses in the brains of SuperAgers to grasp how their immune cells react to disease and adapt to stress. Inflammation is primary in cell loss related to Alzheimer’s and several other neurodegenerative conditions.</p>
<p>In comparison to same-age counterparts, SuperAgers possess fewer activated microglia—the primary immune cells in the brain—within their white matter. White matter functions as the brain’s communication highway.</p>
<p>Essentially, microglia activate in response to detrimental antigens or diseases in the brain. Yet sometimes they can become overly active, causing inflammation and potential damage.</p>
<p>Interestingly, SuperAgers showcase fewer activated microglia, with numbers comparable to those of individuals in their 30s, 40s, and 50s. This could indicate a cleaner brain environment for SuperAgers, where there are fewer toxins or diseases for the microglia to act against. Alternatively, it’s possible that the microglia are simply more efficient at clearing out such issues, allowing them to activate, respond, and then return to a resting state more effectively.</p>
<p>It’s all quite intriguing—suggesting that the immune functions of a SuperAger's brain may very well be more resilient and adaptable, akin to the neuron layers we’ve analyzed in the entorhinal cortex.</p>
<p><strong>CNN: It seems like genetics plays a big role in brain protection. What does that mean moving forward?</strong></p>
<p><strong>Gefen:</strong> Genetics can be quite complex. It’s not simply a matter of having a gene; it also involves how both internal and external factors interact to activate or suppress a gene’s expression. This is where the epigenetics aspect kicks in.</p>
<p>We're currently assessing specific candidate genes that play roles in longevity, cellular repair, cognitive reserves, and more.</p>
<p>I find this enormously exciting—not just the inherited genetics from parents, but also the cellular genetics that empower neurons and immune cells to fulfill their functions. With rapid advancements in technology, I believe we are on the cusp of finding ways to prevent or modify gene expressions pertaining to brain health.</p>
<p>Clearly, there’s no one-size-fits-all solution for Alzheimer’s. While it would be nice to find a simple answer, it’s just not that straightforward.</p>
<p>Addressing this issue will require collaboration among various teams and specialists to develop a tailored approach for prevention and treatment. It’s a possibility, but it will take time.</p>
