REDOX STATUS OF COENZYME Q <sub>10</sub> IS ASSOCIATED WITH CHRONOLOGICAL AGE (2007)

To the Editor: By developing a method of measuring the oxidized form of coenzyme Q10 (CoQ-10) and the reduced form (CoQH2-10) (Figure 1A) simultaneously in plasma, we demonstrated that the redox status of coenzyme Q10 (%CoQ-10), or the percentage of CoQ-10 in the total amount of coenzyme Q10 (TQ) (Figure 1A and B), is greater in patients with geriatric diseases, including chronic obstructive pulmonary disease (COPD),1 Parkinsonism,2 ischemic heart disease, and liver malignancy.3 Alternatively, a study showed that coenzyme Q10 levels in various organs of older people become lower,4 suggesting that coenzyme Q10 is key to the oxidative stress-associated aging process, although the study did not evaluate the redox status of coenzyme Q10. We thus evaluated the association between the redox status of plasma coenzyme Q10 and chronological aging. (A) Coenzyme Q10 takes two forms: oxidized (CoQ-10) and reduced (CoQH2-10). (B) The redox status of coenzyme Q10 is determined A, or percentage of CoQ-10 (%CoQ-10) to total coenzyme Q10 (TQ=CoQ-10+CoQH2-10), as shown in this equation. %CoQ-10 indicates the systemic oxidative stress because the balance of oxidant and antioxidant defines the oxidative stress in favor of the former. (C) Plasma concentration of CoQ-10, CoQH2-10, and TQ. Plasma CoQ-10 levels increased depending on chronological age. (D) The data over %CoQ-10 values and age are plotted, showing their significant association (P<.001, 95% confidence interval=0.03–0.05). According to the results, expected %CoQ-10 value of people aged 25 is 2.8, increasing to 3.8 and 4.6 in those aged 50 and 70, respectively. One hundred twenty-seven male subjects who were current or ex-workers in an industry, with a mean age±standard deviation of 44.1±1.2, were enrolled, and their plasma was collected and examined. It was confirmed that the participants did not develop any remarkable diseases and survived at least 3 years after sampling. All the participants gave informed consent. The local ethics committee approved this process. Plasma levels of CoQH2-10 and CoQ-10 were determined according to a previously published method with modifications.1-3, 5 Corrected coenzyme Q10 levels were further defined by the division of plasma coenzyme Q10 levels with total cholesterol levels (Chol) (i.e., CoQ-10/Chol, CoQH2-10/Chol, and TQ/Chol), because plasma Chol may influence plasma coenzyme Q10 levels by forming a conjugated form.3-5 As in Figure 1C, plasma CoQ-10 levels were 17.9±6.3 nm (CoQ-10 (nm)/Chol (mm)=3.8±1.3) in subjects aged 20 to 39 (n=61), 21.5±7.3 nm (CoQ-10/Chol=4.6±1.6) in those aged 40 to 59 (n=46), and 31.8±15.5 (CoQ-10/Chol=6.7±3.2) in those aged 60 and older (n=20); the oxidized form of plasma coenzyme Q10 levels, as well as CoQ-10/Chol values, in older participants were significantly greater in the plasma concentration (P<.05). In contrast, plasma levels of CoQH2-10 and CoQH2-10/Chol were independent of age. Plasma Chol levels (4.7 mm) were also independent of age and did not influence coenzyme Q10 levels or its redox status. Therefore, plasma %CoQ-10 levels are significantly greater in older subjects (P<.05): 3.1±0.9 in people aged 20 to 39, 3.6±1.2 in people aged 40 to 59, and 4.7±1.6 in people aged 60 and older. Linear regression analysis of the association between chronological age and %CoQ-10 values confirms this (Figure 1D, 95% confidence interval=0.03–0.05, P<.001). This study, to our knowledge, provides the first evidence of the association between the redox status of coenzyme Q10 and chronological age. Because oxidative stress is the breach of the balance between oxidant and antioxidant in favor of the former,6 the elevation of redox status of coenzyme Q10 indicates an enhancement in systemic oxidative stress. %CoQ-10 has chronological age-specific values (i.e., 2.8 in people aged 25, increasing to 3.8 and 4.6 in people aged 50 and 70, respectively (Figure 1D). This implies that plasma %CoQ-10 values can be useful as a biomarker of aging associated with oxidative stress and that measurement of %CoQ10 will help us assess the individual aging process, because only limited biomarkers are currently available. It has previously been reported that coenzyme Q10 levels decrease in various organs, including the brain, heart, and lung, in older people,4 suggesting that the amount of coenzyme Q10 is critical to the aging process. In contrast, TQ levels in the liver4 and the plasma (Figure 1C) do not become lower in older people, suggesting that the function of the organs is well maintained even in older people. Furthermore, the elevation in plasma %CoQ-10 suggested the role of coenzyme Q10 in the well-maintained organs of older people; CoQH2-10 scavenges the oxidants by becoming oxidized, resulting in the elevation of %CoQ-10 values in older people (Figure 1C and D). In conclusion, we demonstrated that not only its amount, but also the redox status of coenzyme Q10 is essential to balance the oxidative stress associated with the aging process. Furthermore, the %CoQ-10 value is a potential biomarker of the aging process. These implications will be clarified by further studies investigating the change in %CoQ-10 values in individuals as they become older and the effect of oral administration of coenzyme Q10 on the individual aging process. Financial Disclosure: None. Author Contributions: Hiroo Wada and Shin-ichi Hagiwara: study concept, design, acquisition of subjects and data, analysis and interpretation of data, and preparation of manuscripts. Hajime Goto and Yorihiro Yamamoto: study concept, design, analysis, and interpretation of data. Sponsor's Role: None.