Boosting neuronal activity-driven mitochondrial DNA transcription improves cognition in aged mice.
basic_science · Level V
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- Record sourced from PubMed, PMID 39700269.
- Also identified by DOI 10.1126/science.adp6547 and PMC identifier 13064864.
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Abstract
Deciphering the complex interplay between neuronal activity and mitochondrial function is pivotal in understanding brain aging, a multifaceted process marked by declines in synaptic function and mitochondrial performance. Here, we identified an age-dependent coupling between neuronal and synaptic excitation and mitochondrial DNA transcription (E-TC<sub>mito</sub>), which operates differently compared to classic excitation-transcription coupling in the nucleus (E-TC<sub>nuc</sub>). We demonstrated that E-TC<sub>mito</sub> repurposes molecules traditionally associated with E-TC<sub>nuc</sub> to regulate mitochondrial DNA expression in areas closely linked to synaptic activation. The effectiveness of E-TC<sub>mito</sub> weakens with age, contributing to age-related neurological deficits in mice. Boosting brain E-TC<sub>mito</sub> in aged animals ameliorated these impairments, offering a potential target to counteract age-related cognitive decline.
Medical subject headings
- Aging
- Brain
- Cognition
- DNA, Mitochondrial
- Neurons
- Transcription, Genetic