Age-related brain decline is one of the leading causes of disability worldwide, yet its molecular origins remain poorly understood. Among the earliest cellular changes in the aging brain, mitochondrial dysfunction precedes any detectable synaptic loss or functional failure. The mitochondrial genome may play a key role in this process, but whether its molecular state changes during brain aging, and whether those changes contribute to neuronal decline, remains unknown. Using Oxford Nanopore Technology direct sequencing, we will characterise mitochondrial DNA modifications in neurons from young and aged mice. Our objective is to determine whether the mitochondrial genome carries an age-dependent molecular signature that contributes to neuronal dysfunction during brain aging.
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