The ‘Super-Aged’ Brain: Novel Research Reveals Clues to Protecting Memory and Cognition

Many people experience cognitive decline with age, linked to the buildup of defective proteins and subsequent cell death. However, some individuals maintain remarkable mental acuity well into their 80s. Recent research published in Nature offers new insights into this discrepancy, focusing on the brain’s capacity to generate new neurons – a process called neurogenesis – even in advanced age.

What the Study Found

The study identified a group of “super-aged” individuals (those aged 80 or older with the memory capacity of people 30 years younger) who exhibited approximately twice as many new neurons in the hippocampus – a brain region crucial for learning and memory – compared to older adults with typical age-related memory decline. Notably, they had 2.5 times more new neurons than individuals with Alzheimer’s disease .

“This paper shows biological evidence that the aging brain is plastic,” even at age 80, explained Tamar Gefen, an associate professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine, who contributed to the research.

Identifying Neurogenesis in the Aging Brain

Researchers first established genetic markers for neural stem cells, neuroblasts, and immature neurons in the brains of young adults (ages 20-40) with normal cognitive function. These markers support track the progression of new neuron development: neural stem cells act as “babies,” neuroblasts as “teenagers,” and immature neurons as “almost adults,” according to Orly Lazarov, a professor of neuroscience at the University of Illinois College of Medicine at Chicago, who led the research.

These markers were then sought in the brains of four groups of older adults: those with normal cognition, mild cognitive impairment, Alzheimer’s disease, and the “super-aged.” Even as all groups showed evidence of these cell types, the quantities varied significantly and correlated with cognitive function at the time of death.

Resilience in ‘Super-Aged’ Brains

The super-aged individuals displayed a significantly higher number of immature neurons in the hippocampus, even exceeding levels found in young adults. These neurons likewise exhibited unique genetic and epigenetic characteristics suggesting a resilience to the aging process.

“Super aging occurs not only given that there are more of these young cells, but because there is a type of genetic programming” that allows their preservation, Dr. Gefen said.

Implications for Alzheimer’s Research

Interestingly, the study also revealed a pattern in individuals with Alzheimer’s disease. They had more neural stem cells than other older adults, but fewer neuroblasts and immature neurons. This suggests that neurogenesis may be disrupted in Alzheimer’s, with stem cells failing to progress through the developmental stages.

Hongjun Song, a professor of neuroscience at the Perelman School of Medicine at the University of Pennsylvania, who researches neurogenesis but was not involved in the study, suggested this finding “really has opened up a new direction for the field” to potentially treat Alzheimer’s by reactivating dormant stem cells.

Ongoing Debate and Future Research

While the findings are promising, some researchers remain cautious. Shawn Sorrells, an associate professor of neuroscience at the University of Pittsburgh, noted the study shares some methodological limitations with other neurogenesis research and called for validation using additional techniques.

The capacity for neurogenesis in the adult human brain remains a topic of debate. While established in babies, young children, and several animal species, the extent of neurogenesis in adults is still under investigation . This latest study provides new avenues for exploration, with Dr. Lazarov focusing on understanding how the unique immature neurons in the super-aged contribute to their superior memory and exploring potential pharmacological interventions to replicate this effect.