Coenzyme Q10 supplementation improves the motor function of middle-aged mice by restoring the neuronal activity of the motor cortex.

Physiological aging causes motor function decline and anatomical and biochemical changes in the motor cortex. 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 Q10 (CoQ10) as a water-soluble nanoformula by drinking water for 1 week. CoQ10 supplementation concurrently improved brain mitochondrial respiration but not muscle strength. 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 CoQ10 for 1 week but not by administering CoQ10 acutely to brain slices. Interestingly, CoQ10 with high-frequency stimulation induced NMDA receptor-dependent long-term potentiation (LTP) in layer V of the primary motor cortex of middle-aged mice. Importantly, the fEPSP amplitude showed a larger input‒output relationship after CoQ10-dependent LTP expression. These data suggest that CoQ10 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. Thus, CoQ10 supplementation may ameliorate the age-related decline in motor function in humans.

Coffee consumption in aged mice increases energy production and decreases hepatic mTOR levels.

OBJECTIVE: Coffee, one of the world's most consumed beverages, has many benefits. Some studies have reported the effects of coffee on aging. The aim of this study was to investigate the locomotor activity, energy metabolism, and lipid metabolism of aged (20-mo-old) mice given coffee. METHODS: Aged C57 BL/6 NCr mice were divided into three groups: controls that were not given coffee (n = 9), a group that received 0.1% caffeinated coffee (n = 9), and a group that received 0.1% decaffeinated coffee (n = 9). This regimen continued for 17 wk until mice reached the age of 24 mo. RESULTS: Regular and decaffeinated coffee consumption decreased plasma-free fatty acid levels, increased hepatic adenosine triphosphate content, and decreased total mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR) protein content in the liver. However, no differences were found in the protein or activity levels of Akt, adenosine monophosphate-activated protein kinase (AMPK), p70 S6 kinase, or sterol regulatory element-binding protein 1, proteins that are upstream or downstream of the mTOR complex 1 (mTORC1)-related pathways. Regular coffee consumption increased food and water intake, locomotor activity, the volume of carbon dioxide production, and the respiration exchange ratio. CONCLUSION: Regular and decaffeinated coffee consumption decreased hepatic total mTOR and p-mTOR levels independently of Akt and AMPK pathways in aged mice. Because decreased mTORC1 activity is known to have antiaging effects, coffee consumption during old age may retard aging. Moreover, coffee consumption by the aged population had a positive effect on behavioral energy and lipid metabolism.

Human ultrasonic hearing is induced by a direct ultrasonic stimulation of the cochlea.

Ultrasound can be perceived by bone-conduction. The cochlear basal turn is involved in processing bone-conducted ultrasound (BCU) information. Previous studies have suggested that ultrasonic perception is induced by ultrasound itself. In contrast, it has also been suggested that a lower frequency sound is generated in non-linear process during the transmission pathway to the cochlea to induce an auditory sensations. To address this issue, we assessed cisplatin-induced changes in BCU sensitivity at 27, 30 and 33kHz in 20 participants (40 ears) who were scheduled to undergo cisplatin chemoradiation therapy. Following the treatment, 62.5% ears were diagnosed with hearing loss according to the criteria of the American Speech-Language-Hearing Association. As expected, significant increases in sensitivity threshold were observed for air-conducted sounds ranging from 8 to 14kHz. In contrast, the BCU threshold significantly decreased after the treatment. Considering that both air-conducted high-frequency sound and BCU are perceived in the cochlear basal turn, these findings indicate that ultrasonic perception is independent of hearing a lower frequency sound generated in non-linear process. In addition, our findings support the hypothesis that ultrasound itself induces ultrasonic perception in the cochlea. The observed cisplatin-induced increase in BCU sensitivity may be explained by hypersensitivity associated with outer hair cells' disorder.