Unveiling insights about memory from the minds of exceptional elderly individuals, known as 'SuperAgers'
In the heart of Chicago, Sel Yackley, an 85-year-old woman, is living a testament to exceptional cognitive aging. She is one of the 101 SuperAgers, individuals whose memory capacity is similar to someone two to three decades younger, participating in the Northwestern University SuperAging Program (NUSAP).
SuperAging, a condition studied by the Mesulam Center for Cognitive Neurology and Alzheimer's Disease for over a quarter-century, is not solely explained by genetics. It also involves other biological factors such as neuroprotection, neural resilience, immune modulation, and brain structure preservation, all shaped in part by lifestyle and environmental influences.
These SuperAgers, like Sel Yackley, do not have the major risk genes for Alzheimer's disease. Beyond genetic factors alone, SuperAging is a combination of biological mechanisms, cellular resilience, and lifestyle/environmental influences that together preserve cognitive function and brain health into advanced age.
Key biological explanations beyond genetic predisposition include resistance and resilience to neurodegeneration, neuroprotective cellular features, immune system adaptability, brain structural preservation, and environmental and lifestyle influences. SuperAgers either avoid accumulating the typical Alzheimer’s-related plaques and tangles ("resistance") or accumulate them but without detrimental effects on brain function ("resilience").
Their brains have fewer neurofibrillary tangles particularly in cholinergic neurons (critical for memory), thicker cortex especially in the anterior cingulate region linked to motivation and social behavior, and greater numbers of specialized von Economo neurons and larger neurons in the entorhinal cortex crucial for memory. SuperAgers also exhibit lower levels of activated microglia (brain immune cells), suggesting either less brain inflammation or more efficient immune response that swiftly clears toxins without damaging tissue.
Brain imaging shows slower cortical thinning and sometimes thicker cortex in key areas than much younger adults, indicating preserved brain volume and neural integrity beyond what would be expected from age alone. High levels of social engagement, physical activity, cognitive stimulation, and positive emotional well-being are common in SuperAgers, indicating that non-genetic factors interact with biology through epigenetic and systemic pathways to support brain health.
Sel Yackley believes that her active lifestyle and joie de vivre contribute to her youthful cognition. Not all SuperAgers prioritize their health, but they don't take their cognitive fitness for granted. Yackley has made plans to donate her brain to Northwestern's Brain Bank for study, as well as the rest of her body for potential transplant purposes.
Today, the Mesulam Center for Cognitive Neurology and Alzheimer's Disease, located at the Northwestern University Feinberg School of Medicine, has autopsied nearly 80 SuperAger brains and compared them to those of their "neurotypical" peers. Dr. M. Marsel Mesulam, the founder of the Mesulam Center, has been instrumental in this research.
As the number of people living with Alzheimer's disease in the U.S. is projected to increase from more than 7 million to nearly 13 million by 2050, the study of SuperAgers offers hope for understanding the biological underpinnings of exceptional cognitive aging and potentially developing interventions to slow or prevent cognitive decline in the general population.
- Sel Yackley, as a SuperAger participating in the Northwestern University SuperAging Program (NUSAP), has a memory capacity similar to someone decades younger, demonstrating the importance of non-genetic factors like lifestyle and environmental influences in medical-conditions related to health-and-wellness, such as aging and mental-health.
- The SuperAging Program at Northwestern University, led by Dr. M. Marsel Mesulam, is investigating the biological mechanisms of SuperAgers, who exhibit resistance and resilience to neurodegeneration, with lower levels of activated microglia, thicker cortex in key areas, and fewer neurofibrillary tangles in cholinergic neurons, suggesting potential implications for women's-health and managing conditions like Alzheimer's disease.
- In the pursuit of exceptional cognitive aging, Sel Yackley, one of the 101 SuperAgers, believes that her active lifestyle and positive emotional well-being play crucial roles, underscoring the significance of health-and-wellness practices in maintaining mental-health and well-being as we age.
