In this paper, we report results obtained from a continuing clinical trial on the effect of coenzyme Q10 (CoQ10) administration on human vastus lateralis (quadriceps) skeletal muscle. Muscle samples, obtained from aged individuals receiving placebo or CoQ10 supplementation (300mg per day for four weeks prior to hip replacement surgery) were analysed for changes in gene and protein expression and in muscle fibre type composition. Microarray analysis (Affymetrix U95A human oligonucleotide array) using a change in gene expression of 1.8-fold or greater as a cutoff point, demonstrated that a total of 115 genes were differentially expressed in six subject comparisons. In the CoQ10-treated subjects, 47 genes were up-regulated and 68 down-regulated in comparison with placebo-treated subjects. Restriction fragment differential display analysis showed that over 600 fragments were differentially expressed using a 2.0-fold or greater change in expression as a cutoff point. Proteome analysis revealed that, of the high abundance muscle proteins detected (2,086 +/- 115), the expression of 174 proteins was induced by CoQ10 while 77 proteins were repressed by CoQ10 supplementation. Muscle fibre types were also affected by CoQ10 treatment; CoQ10-treated individuals showed a lower proportion of type I (slow twitch) fibres and a higher proportion of type IIb (fast twitch) fibres, compared to age-matched placebo-treated subjects. The data suggests that CoQ10 treatment can act to influence the fibre type composition towards the fibre type profile generally found in younger individuals. Our results led us to the conclusion that coenzyme Q10 is a gene regulator and consequently has wide-ranging effects on over-all tissue metabolism. We develop a comprehensive hypothesis that CoQ10 plays a major role in the determination of membrane potential of many, if not all, sub-cellular membrane systems and that H2O2 arising from the activities of CoQ10 acts as a second messenger for the modulation of gene expression and cellular metabolism.