A multi-institutional study published in the journal Nature has identified that older adults with exceptional cognitive abilities, known as "superagers," produce significantly more new neurons in the hippocampus than their peers.
The research, conducted by scientists at the University of Illinois Chicago (UIC), Northwestern University, and the University of Washington, provides new insights into the biological mechanisms underlying cognitive resilience in advanced age.
Key Findings
The study found that superagers—defined as individuals aged 80 or older with memory capacity comparable to people two to three decades younger—exhibited twice the rate of neurogenesis (the birth of new neurons) compared to cognitively healthy older adults.
Superagers produced 2.5 times more new neurons than individuals with Alzheimer's disease. Notably, superager brains contained more newly developed neurons than healthy adults in their 30s and 40s.
In contrast, brain samples from individuals with preclinical cognitive decline showed minimal neurogenesis, and those with Alzheimer's disease generated almost no new neurons.
Study Methodology
Researchers analyzed donated brain samples from 38 individuals across five groups:
- Healthy adults aged 40 and younger
- Healthy older adults
- Superagers (aged 80+ with superior memory)
- Individuals with early cognitive decline
- Individuals diagnosed with Alzheimer's disease
Superager brains were provided by Northwestern University's SuperAging Program, which has followed 290 participants and analyzed 77 donated brains over 25 years. Other samples were provided by the University of Washington.
The study utilized multiomic single-cell sequencing to measure three stages of developing neurons in the hippocampi: stem cells, neuroblasts, and immature neurons. This technique identified specific brain cells crucial for memory and cognition in the aging hippocampus.
Biological Mechanisms
The research identified two primary mechanisms in superagers: resistance (absence of amyloid and tau proteins) and resilience (presence of proteins without cognitive decline). Key findings include:
- CA1 neurons: Essential for memory consolidation and retrieval, these cells are among the first affected by tau tangles in Alzheimer's disease. In superagers, they showed enhanced function.
- Astrocytes: These cells, which outnumber neurons, regulate blood flow and promote synapse formation. In superagers, astrocytes and CA1 neurons coordinated to boost synapse signaling, creating an enriched cellular environment.
- Epigenetic signatures: New neurons in superagers exhibited distinct epigenetic markers based on cognitive health status.
Previous Research on Superagers
Earlier studies from the Northwestern SuperAging Program identified additional characteristics of superagers:
- A thicker cingulate cortex compared to people in their 50s and 60s
- Three times fewer tau tangles in the hippocampus
- Larger, healthier neurons in the entorhinal cortex, surpassing the size of neurons in much younger individuals
- More von Economo neurons, linked to social behavior
- Slower brain shrinkage compared to peers
- Fewer activated microglia (brain immune cells), similar to levels seen in individuals 30 to 40 years younger
- Self-reported traits including extroversion, adaptability, openness to new experiences, and low neuroticism levels
Study Limitations
Researchers noted the study had a small sample size and that variability among human brain samples is common.
Implications and Future Research
First author Ahmed Disouky stated that the study suggests the aging brain is not fixed in its decline and can maintain neurogenesis. Co-lead author Dr. Jalees Rehman noted that understanding the molecular and epigenetic aspects of neurogenesis could inform targeted therapies to preserve memory and cognitive function in aging adults.
The research team plans to investigate environmental and lifestyle factors, including diet, exercise, and inflammation, that may interact with neurogenesis to influence aging.
Maintaining Brain Health
While superagers may have genetic advantages, experts not involved in the study suggested that lifestyle factors can support brain health.
Dr. Richard Isaacson, an Alzheimer's prevention researcher, highlighted that lifestyle changes including diet, exercise, stress reduction, optimized sleep, and managing vascular risk factors may promote brain area growth and reduce signs of Alzheimer's disease.
Dr. Jennifer Pauldurai of the Inova Brain Health and Memory Disorders Program recommended active cognitive engagement, physical activity, management of chronic illnesses, and addressing mental trauma to support neuron growth.
The findings were published in the journal Nature.