Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and an antioxidant in plasma membranes and lipoproteins. It is endogenously produced in all cells by a highly regulated pathway that involves a mitochondrial multiprotein complex. Defects in either the structural and/or regulatory components of CoQ complex or in non-CoQ biosynthetic mitochondrial proteins can result in a decrease in CoQ concentration and/or an increase in oxidative stress. Besides CoQ10 deficiency syndrome and aging, there are chronic diseases in which lower levels of CoQ10 are detected in tissues and organs providing the hypothesis that CoQ10 supplementation could alleviate aging symptoms and/or retard the onset of these diseases. Here, we review the current knowledge of CoQ10 biosynthesis and primary CoQ10 deficiency syndrome, and have collected published results from clinical trials based on CoQ10 supplementation. There is evidence that supplementation positively affects mitochondrial deficiency syndrome and the symptoms of aging based mainly on improvements in bioenergetics. Cardiovascular disease and inflammation are alleviated by the antioxidant effect of CoQ10. There is a need for further studies and clinical trials involving a greater number of participants undergoing longer treatments in order to assess the benefits of CoQ10 treatment in metabolic syndrome and diabetes, neurodegenerative disorders, kidney diseases, and human fertility.

Mitochondria are key in the metabolism of aerobic organisms and in ageing progression and age-related diseases. Mitochondria are essential for obtaining ATP from glucose and fatty acids but also in many other essential functions in cells including aminoacids metabolism, pyridine synthesis, phospholipid modifications and calcium regulation. On the other hand, the activity of mitochondria is also the principal source of reactive oxygen species in cells. Ageing and chronic age-related diseases are associated with the deregulation of cell metabolism and dysfunction of mitochondria. Cell metabolism is controlled by three major nutritional sensors: mTOR, AMPK and Sirtuins. These factors control mitochondrial biogenesis and dynamics by regulating fusion, fission and turnover through mito- and autophagy. A complex interaction between the activity of these nutritional sensors, mitochondrial biogenesis rate and dynamics exists and affect ageing, age-related diseases including metabolic disease. Further, mitochondria maintain a constant communication with nucleus modulating gene expression and modifying epigenetics. In this review we highlight the importance of mitochondria in ageing and the repercussion in the progression of age-related diseases and metabolic disease.

Fatty acids and glucose are the main bioenergetic substrates in mammals that are alternatively used during the transition between fasting and feeding. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2, a member of the aarF domain-containing mitochondrial protein kinase family, in human is associated with liver dysfunction and severe mitochondrial myopathy with lipid droplets in skeletal muscle. In order to better understand the etiology of this rare disorder, we generated a heterozygous Adck2 knockout mouse model to perform in vivo and cellular studies using integrated analysis of physiological and omics data (transcriptomics-metabolomics). The data show that Aldh2+/- mice exhibits impaired fatty acid oxidation, liver dysfunction, and mitochondrial myopathy in skeletal muscle resulting in lower physical performance. Significant decrease in CoQ biosynthesis was observed and supplementation with CoQ partially rescued the phenotype both in the human subject and mouse model. These results indicate that ADCK2 is involved in organismal fatty acid metabolism and in CoQ biosynthesis in skeletal muscle. We propose that patients with isolated myopathies and myopathies involving lipid accumulation be tested for possible ADCK2 defect as they are likely to be responsive to CoQ supplementation.

Fatty acids and glucose are the main bioenergetic substrates in mammals. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2, a member of the aarF domain-containing mitochondrial protein kinase family, in human is associated with liver dysfunction and severe mitochondrial myopathy with lipid droplets in skeletal muscle. In order to better understand the etiology of this rare disorder, we generated a heterozygous Adck2 knockout mouse model to perform in vivo and cellular studies using integrated analysis of physiological and omics data (transcriptomics–metabolomics). The data showed that Adck2+/− mice exhibited impaired fatty acid oxidation, liver dysfunction, and mitochondrial myopathy in skeletal muscle resulting in lower physical performance. Significant decrease in Coenzyme Q (CoQ) biosynthesis was observed and supplementation with CoQ partially rescued the phenotype both in the human subject and mouse model. These results indicate that ADCK2 is involved in organismal fatty acid metabolism and in CoQ biosynthesis in skeletal muscle. We propose that patients with isolated myopathies and myopathies involving lipid accumulation be tested for possible ADCK2 defect as they are likely to be responsive to CoQ supplementation.

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Introduction:The objective of this study was to analyze the effect of caffeine ingestion in soccer performance, particularly in the countermovement jump test (CMJ). Material and Methods:A total of 17 players from a U-19 amateur Spanish team participated in this pilot study. A double-blind placebo-controlled randomized experimental design was used in 2 different sessions (1.5 hour per session) separated by 1 week. CMJ was collected at the beginning and at the end of sessions; Rating of Perceived Exertion (RPE) was recorded. Players ingested caffeine or placebo at the beginning of session (minute 0 of session), providing a total of 4mg of caffeine or a placebo per kg of body mass. Side effects from caffeine and placebo ingestions were analyzed. The effect sizes (ES) were calculated using values for Cohen's and Quantitative differences were assessed qualitatively (QA). Results:The jump height with caffeine supplementation at the beginning of training was 37.03 (±3.87) cm and at the end was 39.35 (±4.05) cm, obtaining significant improvements (p<0.05; ES:0.56; QA:99/1/0). Significant differences on CMJ at the end of the training session between caffeine and placebo groups were observed (39.35 [±4.05] cm vs. 36.85 [±3.15] cm; p<0.05; ES:0.65; QA:0/1/99). Significant differences on RPE between groups were observed. A nonsignificant tendency to suffer more side effects with caffeine ingestion was obtained. Conclusions:This study shows how the ingestion of 4mg of caffeine per kg of body mass could be an ergogenic aid to improve soccer performance. However, further studies with bigger soccer players sample would be necessary to refute the present results. Más información: http://creativecommons.org/licenses/by-nc-sa/4.0/ Introducción: El objetivo del presente estudio fue analizar el efecto de la ingestión de cafeína en el rendimiento en fútbol, específicamente en el test de salto en contramovimiento (CMJ).Material y Métodos: 17 jugadores de la categoría Sub-19 de un equipo amateur español participaron en el estudio piloto. Se siguió un diseño a doble ciego, placebo-control, aleatorizado en 2 entrenamientos (1,5 horas/sesión) separados por 1 semana. El CMJ se recogió al inicio y, al final de las sesiones, la tasa de esfuerzo percibido (RPE) fue recogida. Los jugadores tomaron cafeína o placebo al inicio del entrenamiento (minuto 0), proveyendo 4mg/kg de masa corporal de cafeína o placebo. Se analizaron los efectos secundarios provenientes de la cafeína y del placebo. Los tamaños de efecto (ES) se calcularon utilizando valores para Cohen y las diferencias cuantitativas se evaluaron cualitativamente (QA).Resultados: La altura del salto media cuando se ingirió cafeína fue 37,03 (±3,87) cm al inicio y 39,35 (±4,05) cm al final del entrenamiento, obteniendo una mejora significativa (p<0,05; ES:0,56; QA:99/1/0). Se observaron diferencias significativas en el CMJ al final de los entrenamientos entre la ingestión con cafeína y placebo (39,35 [±4,05] cm vs. 36,85 [±3,15] cm; p<0,05; ES:0,65; QA:0/1/99). Se obtuvieron diferencias...

Coenzyme Q is a unique lipidic molecule highly conserved in evolution and essential to maintaining aerobic metabolism. It is endogenously synthesized in all cells by a very complex pathway involving a group of nuclear genes that share high homology among species. This pathway is tightly regulated at transcription and translation, but also by environment and energy requirements. Here, we review how coenzyme Q reacts within mitochondria to promote ATP synthesis and also integrates a plethora of metabolic pathways and regulates mitochondrial oxidative stress. Coenzyme Q is also located in all cellular membranes and plasma lipoproteins in which it exerts antioxidant function, and its reaction with different extramitochondrial oxidoreductases contributes to regulate the cellular redox homeostasis and cytosolic oxidative stress, providing a key factor in controlling various apoptosis mechanisms. Coenzyme Q levels can be decreased in humans by defects in the biosynthesis pathway or by mitochondrial or cytosolic dysfunctions, leading to a highly heterogeneous group of mitochondrial diseases included in the coenzyme Q deficiency syndrome. We also review the importance of coenzyme Q levels and its reactions involved in aging and age-associated metabolic disorders, and how the strategy of its supplementation has had benefits for combating these diseases and for physical performance in aging.

Resveratrol (RSV) is a bioactive natural molecule that induces antioxidant activity and increases protection against oxidative damage. RSV could be used to mitigate damages associated to metabolic diseases and aging. Particularly, RSV regulates different aspects of mitochondrial metabolism. However, no information is available about the effects of RSV on Coenzyme Q (CoQ), a central component in the mitochondrial electron transport chain. Here, we report for the first time that RSV modulates COQ genes and parameters associated to metabolic syndrome in mice. Mice fed with high fat diet (HFD) presented a higher weight gain, triglycerides (TGs) and cholesterol levels while RSV reverted TGs to control level but not weight or cholesterol. HFD induced a decrease of COQs gene mRNA level, whereas RSV reversed this decrease in most of the COQs genes. However, RSV did not show effect on CoQ9, CoQ10 and total CoQ levels, neither in CoQ-dependent antioxidant enzymes. HFD influenced mitochondrial dynamics and mitophagy markers. RSV modulated the levels of PINK1 and PARKIN and their ratio, indicating modulation of mitophagy. In summary, we report that RSV influences some of the metabolic adaptations of HFD affecting mitochondrial physiology while also regulates COQs gene expression levels in a process that can be associated with mitochondrial dynamics and turnover.