Curious about how aging affects brain function? Discover how neuronal hyperactivity influences cognitive decline & how dietary changes help!
A study from Nagoya University has identified excessive neuronal activation—rather than reduced activity—as a central factor in age-related cognitive decline.
Published in the Proceedings of the National Academy of Sciences, the research points to prolonged overactivation of specific neurons as a key contributor to aging in the brain. This finding opens the door to lifestyle strategies, including dietary adjustments, that may support long-term brain health by moderating neural activity.
Cognitive performance depends on a well-balanced network of neurons working in harmony. For years, cognitive decline with age was thought to result from diminishing neuronal function. This new perspective shifts the focus toward the impact of overstimulation in certain brain cells over time.
In related investigations, nematode models were used to explore how excessive neuronal firing relates to the loss of brain function during aging. These experiments, led by Associate Professor Kentaro Noma, provide evidence that hyperactivity in specific neurons emerges with age and may drive functional decline.
“Brain aging may not stem from doing too little—but rather from doing too much for too long.”
Kentaro Noma
Using Nematodes to Explore Brain Aging
“In this study, the nematode Caenorhabditis elegans was used. Measuring only one millimeter in length and living just two weeks, this organism exhibits diverse behaviors through a network of 302 neurons,” noted Noma. “Many genes and biological mechanisms are shared between C. elegans and humans. Therefore, it was considered that the factors influencing cognitive decline in C. elegans might also be relevant in humans.”
The study focused on a learning behavior called thermotaxis. When exposed to a temperature gradient ranging from 17 to 23 degrees Celsius, nematodes previously kept at 23 degrees with food tend to move toward that temperature. In contrast, when food is absent, this response changes. This behavior indicates the capacity of C. elegans to associate environmental temperature with the presence or absence of nourishment.
“Previous findings suggested that age-related decline in associative learning was linked to reduced neuronal activity. However, recent observations revealed that the activity of AFD sensory neurons and AIY interneurons—key players in this learning process—showed little change with aging.”
Binta Maria Aleogho
These results suggest that cognitive aging may not result from decreased brain cell activity, but rather from different neural mechanisms, possibly including overstimulation.
The Impact of Neuronal Hyperactivation on Aging
The study then focused on the behavior of C. elegans when six types of neurons, believed to be involved in associative learning—AWC and ASI sensory neurons, along with AIZ, AIB, RIA, and AIA interneurons—were removed. Surprisingly, after removing either AWC or AIA neurons, the nematodes were still able to navigate to the 23-degree location.
The activities of neurons in aging nematodes were also measured. It was observed that AWC and AIA neurons become excessively activated as the nematodes age. “This suggests that the hyperactivation of these two types of neurons with age disrupts the normal neural network, preventing the proper execution of thermotaxis behavior,” explained Noma.
Additionally, neuronal hyperactivation and behavioral decline in older nematodes were suppressed by altering their food source to a different type of bacteria. “This suggests that diet changes might play a role in preventing brain aging in humans,” Noma added.
“Traditionally, focus has been placed on the decline in neuronal activity as people age. Our findings may shift attention to the hyperactivation of neurons. Future research will continue with C. elegans to explore ways to reduce neuron hyperactivation and improve brain function, which could deepen understanding of the aging process in the brain.”
Kentaro Noma
https://doi.org/10.1073/pnas.2412391122
Summary
This study investigates the role of neuronal hyperactivity in the age-dependent decline of sensory function, memory, and cognition. It identifies a causal link between excessive neuronal activity and the deterioration of thermotaxis, an associative learning behavior, in aging. The research shows that a pair of sensory neurons (AWC) and interneurons (AIA), though not essential for thermotaxis, become hyperactive over time and contribute to the decline in this behavior. Interestingly, modifying the diet of the animals can suppress this hyperactivity and improve behavior. The findings suggest that neuronal hyperactivity, rather than reduced activity, may drive cognitive decline with age and that dietary changes might help mitigate these effects by reducing neuronal hyperactivity.