Water-soluble CoQ10 as A Promising Anti-aging Agent for Neurological Dysfunction in Brain Mitochondria.

Mayumi Takahashi,Kazuhide Takahashi

doi:10.3390/antiox8030061

Mayumi Takahashi, Kazuhide Takahashi

Open Access

https://doi.org/10.3390/antiox8030061

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Journal: Antioxidants	Publication Date: Mar 11, 2019
Citations: 16	License type: CC BY 4.0

Affiliation: Tokyo Metropolitan Institute of Gerontology

Abstract

Mitochondrial function has been closely associated with normal aging and age-related diseases. Age-associated declines in mitochondrial function, such as changes in oxygen consumption rate, cytochrome c oxidase activity of complex IV, and mitochondrial coenzyme Q (CoQ) levels, begin as early as 12 to 15 months of age in male mouse brains. Brain mitochondrial dysfunction is accompanied by increased accumulation of phosphorylated α-synuclein in the motor cortex and impairment of motor activities, which are similar characteristics of Parkinson’s disease. However, these age-associated defects are completely rescued by the administration of exogenous CoQ10 to middle-aged mice via its water solubilization by emulsification in drinking water. Further efforts to develop strategies to enhance the biological availability of CoQ10 to successfully ameliorate age-related brain mitochondrial dysfunction or neurodegenerative disorders may provide a promising anti-aging agent.

Highlights

Mitochondria in eukaryotes function to regulate cellular metabolism and produce adenosine5’-triphosphate (ATP) through aerobic respiration [1]
Is restoration of mitochondrial function, which includes mitochondrial coenzyme Q (CoQ) levels, optic atrophy 1 (OPA1) binding to complex IV, and cytochrome c oxidase and oxygen consumption activities of complex IV, by water-soluble CoQ10 supplementation accompanied by amelioration of neurological alterations in the motor cortices? Administration of water-soluble CoQ10 via drinking water significantly decreases the number of Ser129-phosphorylated α-syn-positive neurons and increases the vesicular glutamate transporter 1 (VGluT1) levels in the motor cortices of middle-aged mice to levels comparable to those in young mice [12]
The age-associated mitochondrial dysfunction and the accompanying behavioral and pathophysiological defects due to the CoQ deficiency are rescued by oral administration of water-soluble CoQ10, as described above [10,12,21]

Summary

Introduction

Mitochondria in eukaryotes function to regulate cellular metabolism and produce adenosine. The ATP production is achieved by oxidizing β-nicotinamide-adenine dinucleotide reduced form (NADH) and succinate, which are generated in the mitochondrial matrix as the products of metabolism, followed by sequential electron transfer in the electron transport chain (ETC) through four respiratory enzymatic complexes I-IV. This process of mitochondrial respiration is mediated by two electron transporters coenzyme Q (CoQ) and cytochrome c. We review the recent findings concerning age-associated declines in mitochondrial function and the resultant behavioral and physio-pathological alterations that occur in middle-aged (12–15 months of age) mice. The age-associated declines in mitochondrial function are concomitant with reduced levels of mitochondrial CoQ. We propose that CoQ is a promising anti-aging agent for neurological dysfunction in brain mitochondria of mice

Age-associated Decline in Brain Mitochondrial Function and Motor Impairment

Conclusions