The impact of α-lipoic acid, coenzyme Q10, and caloric restriction on life span and gene expression patterns in mice
University of Alabama at Birmingham, Birmingham, Alabama, United States Free Radical Biology and Medicine
(Impact Factor: 5.74).
04/2004; 36(8):1043-57. DOI: 10.1016/j.freeradbiomed.2004.01.015
We evaluated the efficacy of three dietary interventions started at middle age (14 months) to retard the aging process in mice. These were supplemental alpha-lipoic acid (LA) or coenzyme Q(10) (CQ) and caloric restriction (CR, a positive control). LA and CQ had no impact on longevity or tumor patterns compared with control mice fed the same number of calories, whereas CR increased maximum life span by 13% (p <.0001) and reduced tumor incidence. To evaluate these interventions at the molecular level, we used microarrays to monitor the expression of 9977 genes in hearts from young (5 months) and old (30 months) mice. LA, CQ, and CR inhibited age-related alterations in the expression of genes involved in the extracellular matrix, cellular structure, and protein turnover. However, unlike CR, LA and CQ did not prevent age-related transcriptional alterations associated with energy metabolism. LA supplementation lowered the expression of genes encoding major histocompatibility complex components and of genes involved in protein turnover and folding. CQ increased expression of genes involved in oxidative phosphorylation and reduced expression of genes involved in the complement pathway and several aspects of protein function. Our observations suggest that supplementation with LA or CQ results in transcriptional alterations consistent with a state of reduced oxidative stress in the heart, but that these dietary interventions are not as effective as CR in inhibiting the aging process in the heart.
Available from: Simone Onur
- "Furthermore, CoQ10 is necessary for pyrimidine biosynthesis while also being a cofactor for uncoupling proteins
. It has also been identified as a modulator of gene expression
[4-6], inflammatory processes
[7-9] and apoptosis
[10,11]. The reduced form of CoQ10, ubiquinol (Q10H2), serves as a potent antioxidant in mitochondria and lipid membranes as well as a regenerator of other lipid soluble antioxidants
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ABSTRACT: BackgroundThe reduced form of Coenzyme Q10 (CoQ10), ubiquinol (Q10H2), serves as a potent antioxidant in mitochondria and lipid membranes. There is evidence that Q10H2 protects against oxidative events in lipids, proteins and DNA. Serum gamma-glutamyltransferase (GGT) activity is associated with cardiovascular diseases. In a physiological range, activity of GGT is a potential early and sensitive marker of inflammation and oxidative stress.In this study, we first examined the relationship between CoQ10 status and serum GGT activity in 416 healthy participants between 19 and 62 years of age in a cross-sectional study (cohort I). In the second step, 53 healthy males (21–48 years of age; cohort II) underwent a 14-day Q10H2 supplementation (150 mg/d) to evaluate the effect of Q10H2 supplementation on serum GGT activity and GGT1 gene expression.FindingsThere was a strong positive association between CoQ10 status and serum GGT activity in cohort I. However, a gender-specific examination revealed differences between male and female volunteers regarding the association between CoQ10 status and serum GGT activity. Q10H2 supplementation (cohort II) caused a significant decrease in serum GGT activity from T0 to T14 (p < 0.001). GGT1 mRNA levels declined 1.49-fold after Q10H2 supplementation. Of note, other liver enzymes (i.e., aspartate aminotransferase, AST) were not affected by Q10H2 supplementation.ConclusionsCoQ10 level is positively associated with serum GGT activity. Supplementation with Q10H2 reduces serum GGT activity. This effect might be caused by gene expression. Overall, we provide preliminary evidence that higher Q10H2 levels improve oxidative stress via reduction of serum GGT activity in humans.Trial registrationCurrent Controlled Trials
Available from: Gerald Rimbach
- "Received 17 December 2013; accepted 24 January 2014 DOI 10.1002/biof.1160 Published online 27 February 2014 in Wiley Online Library (wileyonlinelibrary.com) biosynthesis as well as a cofactor of uncoupling proteins  and has also been identified as a modulator of gene expression   , inflammatory processes   , and apoptosis  . Due to these roles, deficiency of CoQ is involved in several diseases most of them associated with the ageing process including neuromuscular disorders . "
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ABSTRACT: Coenzyme Q derivatives (CoQ) are lipid soluble antioxidants that are synthesized endogenously in almost all species and function as an obligatory cofactor of the respiratory chain. There is evidence that CoQ status is altered by age in several species. Here we determined level and redox-state of CoQ in different age groups of pigs, mice and Caenorhabditis elegans. Since these species are very different with respect to lifespan, reproduction and physiology, our approach could provide some general tendencies of CoQ status in ageing organisms. We found that CoQ level decreases with age in pigs and mice, whereas CoQ content increases in older worms. As observed in all three species, ubiquinone, the oxidized form of CoQ, increases with age. Additionally, we were able to show that supplementation of ubiquinol-10, the reduced form of human CoQ10 , slightly increases lifespan of post-reproductive worms. In conclusion, the percentage of the oxidized form of CoQ increases with age indicating higher oxidative stress or rather a decreased anti-oxidative capacity of aged animals. © 2014 BioFactors, 2014.
Available from: Chen Hou
- "Species Treatment 1 Treatment 2 M1 (g) M2 (g) LS1 (days) LS2 (days) References Balb/C mice DR started at 22-day old DR started at 120-day old 29.3 29.2 641 647 Stoltzner (1977) B/W mice Free fed; 49% protein in diet; same calorie as treatment 2 Free fed; 15% protein in diet; same calorie as treatment 1 38 38.6 280 295 Gajjar et al. (1987) C57BL/6 mice Add Alpha lipoic acid to diet add Coenzyme Q10 to diet 44 44 939 926 Lee et al. (2004) "
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ABSTRACT: Understanding the trade-offs between organisms' life history traits has been a major goal of physiology, ecology and evolution. In the last few decades, two types of intra-specific studies have highlighted the trade-off between growth and longevity. First, diet restriction (DR), as an environmental intervention, has been shown to suppress growth and extend the lifespan of a broad range of animals. Second, genetic studies have also shown that mice, whose growth hormone function is genetically modified (GM), grow slower and live longer than their wild-type siblings. Despite a wealth of empirical data, still largely missing is a theoretical framework that specifies and makes quantitative predictions on this trade-off. Here, I present a mechanistic model based on the principles of energy conservation. The model quantifies explicitly how DR and GM alter the animal's energy budget, and channel metabolic energy to somatic maintenance by suppressing growth, thereby extending lifespan. Data from a diverse set of empirical studies on small rodents supports the predictions of the model. More importantly, the model reveals that although DR and GM are two different methods to extend lifespan, i.e., environmental vs. genetic, the underlying mechanisms of them are the same from the energetic viewpoint.
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