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Researchers from Nagoya University in Japan have conducted a study examining nematodes, revealing that cognitive decline associated with aging is linked to the overactivation of specific neurons rather than a reduction in overall neuronal function. This research, featured in the journal Proceedings of the National Academy of Sciences, indicates that potential interventions like dietary modifications could help alleviate cognitive deterioration related to aging.
Effective brain function is contingent upon the proper connectivity and interaction of numerous neurons. Traditionally, age-related declines in cognitive abilities have been attributed to a decrease in neuronal activity. However, another facet of aging has emerged: certain neurons in humans appear to become increasingly active as individuals age.
The research team, led by Associate Professor Kentaro Noma, focused on the nematode Caenorhabditis elegans, a minuscule organism measuring about one millimeter in length with a lifespan of only two weeks. According to Noma, “C. elegans displays a range of behaviors governed by its 302 neurons and shares a significant number of genes and biological mechanisms with humans. This resemblance led us to hypothesize that findings on cognitive decline in C. elegans might be applicable to humans.”
The study capitalized on C. elegans‘ ability to learn through a process known as thermotaxis. When these nematodes are placed in a setting with food at 23 degrees Celsius, they instinctively navigate toward that temperature from a cooler environment, unless they find themselves in a food-scarce area. This ability illustrates how C. elegans associates temperature with the presence of food.
First author of the study, Binta Maria Aleogho, noted, “Our earlier research indicated that the capacity for associative learning in C. elegans declines as they age, which we initially believed was due to reduced neuronal activity. However, our recent findings show that the activities of key neurons involved in this learning type, namely the AFD sensory neurons and AIY interneurons, remain largely stable with age.”
The team further investigated the roles of six neuron types essential for associative learning and found surprising results. Upon removing either the AWC or AIA neurons from aged nematodes, their ability to move toward the 23-degree location remained intact.
When assessing neuronal activity in older nematodes, the researchers discovered that both AWC and AIA neurons exhibit heightened spontaneous activation as they age. Noma explained, “This hyperactivation likely disrupts normal neuronal function, impairing the nematodes’ ability to successfully execute thermotaxis behavior.”
Moreover, by altering the nematodes’ diet to include different bacterial food sources, the team successfully reduced neuronal hyperactivation and curbed cognitive decline in older specimens. Noma suggested that if similar dietary interventions can be applied to humans, it may aid in preserving brain function as one ages.
He concluded, “Traditionally, research has concentrated on the waning activity of neurons with age. Our findings prompt a shift in focus toward understanding the implications of neuronal hyperactivation. We plan to continue our investigations with C. elegans to find methods to mitigate this hyperactivation, which could enhance brain function and shed light on the aging process itself.”
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