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), which operates differently compared to classic excitation-transcription coupling in the nucleus (E-TC). We demonstrated that E-TC repurposes molecules traditionally associated with E-TC to regulate mitochondrial DNA expression in areas closely linked to synaptic activation. The effectiveness of E-TC weakens with age, contributing to age-related neurological deficits in mice. Boosting brain E-TC in aged animals ameliorated these impairments, offering a potential target to counteract age-related cognitive decline.
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http://dx.doi.org/10.1126/science.adp6547 | DOI Listing |
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