CoQ10 and Aging

Abstract

The aging process includes impairment in mitochondrial function, a reduction in anti-oxidant activity, and an increase in oxidative stress, marked by an increase in reactive oxygen species (ROS) production. Oxidative damage to macromolecules including DNA and electron transport proteins likely increases ROS production resulting in further damage. This oxidative theory of cell aging is supported by the fact that diseases associated with the aging process are marked by increased oxidative stress. Coenzyme Q10 (CoQ₁₀) levels fall with aging in the human but this is not seen in all species or all tissues. It is unknown whether lower CoQ₁₀ levels have a part to play in aging and disease or whether it is an inconsequential cellular response to aging. Despite the current lay public interest in supplementing with CoQ₁₀, there is currently not enough evidence to recommend CoQ₁₀ supplementation as an anti-aging anti-oxidant therapy.

Keywords: age-related diseases; aging; coenzyme Q10; mitochondrial dysfunction.

Figure 1

Redox forms of CoQ_10. ubiquinone (oxidized form), ubiquinol (reduced form), and semiquinone (semi-oxidized). The Q cycle within the matrix membrane allows proton transfer from the mitochondrial matrix to the intermembrane space helping to generate the electrochemical gradient for ATP production.

Figure 2

The Multiple Roles of Ubiquinone in the Cell.

Figure 3

Schematic representation of CoQ biosynthesis. The isoprenoid side-chain derives from the cholesterol and dolichol synthetic pathway from mevalonate, the benzoquinone ring is derived from tyrosine metabolism. The star symbolizes the genes involved in the final synthesis of CoQ₁₀.

Figure 4

Proposed mechanism by which ubiquinol improves metabolic function and inhibits insulin resistance in KKAy mice (a mouse model of obesity and diabetes). Ubiquinol inhibited phosphorylation of CaMKII (Ca2+/calmodulin-dependent protein kinase II) in the liver resulting in inhibition of C-FOS transcriptional activity and inhibition of PDE4 gene expression. Increased cAMP increases AMPK (AMP-activated protein kinase) activity resulting in SIRT1 and PGC-1α increased mitochondrial function and inhibition of lipid synthesis. (Adapted from Xu H. et al. 2017 [106] with permission).

Figure 5

Age-related decline in the oxygen consumption rate in epithelial tissue measured 16 h after collection in a Seahorse XF analyzer. The gray circles show treated samples, the white circles untreated samples, and the connected circles represent samples from the same donor. Significant improvement with 100 μM CoQ₁₀ incubation. (Adapted from Schniertshauer et al. 2018 [70] with permission).