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New research reveals a promising mechanism to address cognitive decline in aging and neurodegenerative diseases like Alzheimer’s.
Scientists have made a groundbreaking discovery that may offer new hope for combating age-related cognitive decline. In a recent study, researchers identified a crucial link between neuronal activity and mitochondrial function, uncovering a potential strategy to slow or even reverse the cognitive effects of aging and diseases such as Alzheimer’s.
The research, led by Wenwen Li and colleagues, focuses on mitochondria—the energy-producing organelles in cells. Mitochondria are critical for fueling neurons, the brain’s active cells, by generating adenosine triphosphate (ATP) through a process called oxidative phosphorylation (OXPHOS). As we age, the efficiency of this mitochondrial function decreases, leading to oxidative stress, mitochondrial dysfunction, and ultimately, the cognitive decline that is often associated with aging.
Despite the central role of mitochondria in brain health, understanding the specific mechanisms behind the decline in OXPHOS activity as the brain ages has been elusive. This gap in knowledge has hindered efforts to develop effective therapies for age-related cognitive decline.
To fill this gap, Li and her team explored mitochondrial transcription in the hippocampus of both young and aged mice. Their research uncovered a novel mechanism they termed excitation-mitochondrial DNA transcription coupling (E-TCmito). This mechanism connects neuronal excitation with the transcription of mitochondrial DNA, a process that is vital for maintaining both synaptic function and mitochondrial health.
Unlike the traditional excitation-transcription coupling that occurs in the cell’s nucleus, the E-TCmito coupling plays an essential role in the brain’s aging process. As the brain ages, the effectiveness of this mechanism diminishes, leading to a decline in cognitive function. Remarkably, when the researchers enhanced the E-TCmito coupling in aged mice, they observed significant improvements in cognitive performance.
This finding offers a new therapeutic avenue for addressing cognitive decline in aging. The research highlights E-TCmito as a potential target for future treatments aimed at mitigating the effects of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, which are known to involve mitochondrial dysfunction.
In a related commentary, Deniz Bingul and Scott Owen hailed the study as a major step forward in understanding mitochondrial biology in the aging brain. “The findings raise the possibility of identifying targets for age-related neurocognitive disorders associated with mitochondrial dysfunction, including Alzheimer’s and Parkinson’s diseases,” they wrote.
This research not only deepens our understanding of brain aging but also opens the door for novel interventions that could improve brain health in aging populations.
The study, titled “Boosting neuronal activity-driven mitochondrial DNA transcription improves cognition in aged mice,” was published in Science on December 20, 2024.
Reference: Li, W., Li, J., Li, J., et al. (2024). Boosting neuronal activity-driven mitochondrial DNA transcription improves cognition in aged mice. Science. DOI: 10.1126/science.adp6547
