These impairments in the motor cortex may be part of the underlying mechanism that leads to age-related motor function decline.īrain aging also causes deficits in the mitochondrial oxidative phosphorylation system, producing ATP necessary to fulfill brain neuronal functions 8. In rodents, middle-aged mice show motor function impairment and increased phosphorylation of α-synuclein and a decreased level of vesicular glutamate transporter 1 (VGluT1) in motor cortex compared to those of young adult mice 1, 7. Elderly individuals show a decrease in the firing rate of lower motor neurons, which may be related, at least in part, to decreased activity of the motor cortex. Voluntary activation of skeletal muscles is impaired during aging, especially in elderly individuals who are weak or in poor physical condition 5. In the human motor cortex, physiological aging causes cortical atrophy, altered excitability, and decreased neurotransmitter levels 4, 5, 6. In mice, a decline in motor function was observed in middle-aged mice (15 months old) earlier than the drop in survival rate that typically occurs at approximately 24 months of age 1, 2, 3. The age-related decrease in motor function can be caused by a loss of muscle mass and strength (sarcopenia), denervation of neuromuscular junctions (NMJs), loss of motor neurons in the spinal cord, and reduced function of the brain motor cortex.
Thus, CoQ 10 supplementation may ameliorate the age-related decline in motor function in humans. These data suggest that CoQ 10 restores the motor function of middle-aged mice by improving brain mitochondrial function and the basal fEPSP level of the motor cortex, potentially by enhancing synaptic plasticity efficacy. Importantly, the fEPSP amplitude showed a larger input‒output relationship after CoQ 10-dependent LTP expression.
Interestingly, CoQ 10 with high-frequency stimulation induced NMDA receptor-dependent long-term potentiation (LTP) in layer V of the primary motor cortex of middle-aged mice. Notably, we identified an age-related decline in field excitatory postsynaptic potential (fEPSP) amplitude in the pathway from layers II/III to V of the primary motor area of middle-aged mice, which was restored to the young adult level by supplementing with CoQ 10 for 1 week but not by administering CoQ 10 acutely to brain slices. CoQ 10 supplementation concurrently improved brain mitochondrial respiration but not muscle strength. We confirmed that middle-aged mice at 15–18 months old show motor function decline, which can be restored to the young adult level by supplementing with mitochondrial electron transporter coenzyme Q 10 (CoQ 10) as a water-soluble nanoformula by drinking water for 1 week. Physiological aging causes motor function decline and anatomical and biochemical changes in the motor cortex.
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