Coenzyme Q10 deficiency in patients with hereditary hemochromatosis

AimHereditary hemochromatosis (HH) is a group of inherited disorders that causes a slow and progressive iron deposition in diverse organs, particularly in the liver. Iron overload induces oxidative stress and tissue damage. Coenzyme Q10 (CoQ10) is a cofactor in the electron-transport chain of the mitochondria, but it is also a potent endogenous antioxidant. CoQ10 interest has recently grown since various studies show that CoQ10 supplementation may provide protective and safe benefits in mitochondrial diseases and oxidative stress disorders. In the present study we sought to determine CoQ10 plasma level in patients recently diagnosed with HH and to correlate it with biochemical, genetic, and histological features of the disease. Methods: Plasma levels of CoQ10, iron, ferritin, transferrin and vitamins (A, C and E), liver tests (transaminases, alkaline phosphatase and bilirubin), and histology, as well as three HFE gene mutations (H63D, S654C and C282Y), were assessed in thirty-eight patients (32 males, 6 females) newly diagnosed with HH without treatment and in twenty-five age-matched normolipidemic healthy subjects with no HFE gene mutations (22 males, 3 females) and without clinical or biochemical signs of iron overload or liver diseases.ResultsPatients with HH showed a significant decrease in CoQ10 levels respect to control subjects (0.31 ± 0.03 µM vs 0.70 ± 0.06 µM, p < 0.001, respectively) independently of the genetic mutation, cirrhosis, transferrin saturation, ferritin level or markers of hepatic dysfunction. Although a decreasing trend in CoQ10 levels was observed in patients with elevated iron levels, no correlation was found between both parameters in patients with HH. Vitamins C and A levels showed no changes in HH patients. Vitamin E was significantly decreased in HH patients (21.1 ± 1.3 µM vs 29.9 ± 2.5 µM, p < 0.001, respectively), but no correlation was observed with CoQ10 levels. Conclusion: The decrease in CoQ10 levels found in HH patients suggests that CoQ10 supplementation could be a safe intervention strategy complementary to the traditional therapy to ameliorate oxidative stress and further tissue damage induced by iron overload.     

Mediterranean diet supplemented with coenzyme Q10 induces postprandial changes in p53 in response to oxidative DNA damage in elderly subjects

Coenzyme Q10 (CoQ) is a powerful antioxidant that reduces oxidative stress. We explored whether the quality of dietary fat alters postprandial oxidative DNA damage and whether supplementation with CoQ improves antioxidant capacity by modifying the activation/stabilization of p53 in elderly subjects. In this crossover study, 20 subjects were randomly assigned to receive three isocaloric diets during 4 weeks each: (1) Mediterranean diet (Med diet), (2) Mediterranean diet supplemented with CoQ (Med+CoQ diet), and (3) saturated fatty acid-rich diet (SFA diet). Levels of mRNAs were determined for p53, p21, p53R2, and mdm2. Protein levels of p53, phosphorylated p53 (Ser20), and monoubiquitinated p53 were also measured, both in cytoplasm and nucleus. The extent of DNA damage was measured as plasma 8-OHdG. SFA diet displayed higher postprandial 8-OHdG concentrations, p53 mRNA and monoubiquitinated p53, and lower postprandial Mdm2 mRNA levels compared with Med and Med+CoQ diets (p < 0.05). Moreover, Med+CoQ diet induced a postprandial decrease of cytoplasmatic p53, nuclear p-p53 (Ser20), and nuclear and cytoplasmatic monoubiquitinated p53 protein (p < 0.05). In conclusion, Med+CoQ diet improves oxidative DNA damage in elderly subjects and reduces processes of cellular oxidation. Our results suggest a starting point for the prevention of oxidative processes associated with aging.     

Association between ethanol and sucrose intake in the laboratory mouse: exploration via congenic strains and conditioned taste aversion

BACKGROUND: A substantial body of literature indicates that intakes of "sweet" solutions and ethanol are positively correlated across inbred strains of rats and mice but there has been speculation that the correlation is fortuitous and there is no agreement on the underlying mechanism. METHODS AND RESULTS: We assessed the correlation between intake of sucrose and ethanol in congenic mice created by backcrossing alleles favoring sucrose intake from the BXD RI-5 strain into DBA/2J. In addition, to probe more specifically the interrelationship between intake of the two solutions, we examined aversion generalization from sucrose to ethanol in C57BL/6J mice. Among the congenic mice, a statistically significant product-moment correlation of r = 0.36 (p < 0.02) was found between 6-hr intake of sucrose corrected for differences in baseline water intake and preference for 10% ethanol presented in a 96-hr 2-bottle test. Furthermore, C57BL/6J male mice conditioned to avoid a 0.2 M sucrose solution generalized their aversion to a 10% ethanol solution presented in the same 2-bottle test, drinking 42.1 +/- 9.38% (mean +/- SE) of their total fluid intake from the ethanol tube, compared with the control group mean of 69.86 +/- 8.84%. CONCLUSIONS: The positive association between intake of sucrose and ethanol in congenic mice provides strong evidence that the previously demonstrated genetic correlation between intake of these solutions is not the result of fortuitous fixation of unrelated alleles and provides suggestive evidence that, at least in the B6/D2 lineage, the genetic association between intakes of the two solutions reflects close linkage or the pleiotropic effects of the same genes. The demonstration that a conditioned taste aversion to sucrose generalized to ethanol in the C57BL/6J inbred mouse strain is an extension of similar observations in outbred rats and specifically demonstrates that intake of the two solutions is controlled by some of the same physiologic or neurological processes and thus is consistent with the pleiotropic interpretation of the genetic correlation.     

Effect of coenzyme Q10 administration on endothelial function and extracellular superoxide dismutase in patients with ischaemic heart disease: a double-blind, randomized controlled study.

AIMS: This randomized controlled study was designed to determine whether oral coenzyme Q(10) (CoQ(10)) supplementation (100 mg tid) was able to improve extracellular superoxide dismutase (ecSOD) activity and endothelium-dependent (ED) vasodilation in patients with coronary artery disease (CAD). ecSOD, a major antioxidant enzyme system of the vessel wall, is reduced in patients with CAD. Moreover, there is a strong correlation between endothelium-bound ecSOD and the ED dilation of conduit arteries. CoQ(10) has been recently shown to improve the ED relaxation in diabetic patients. METHODS AND RESULTS: Thirty-eight CAD patients (33 M/5 F, mean age 55 +/- 4 years, ejection fraction 57.5 +/- 8%) were randomized into two groups. One group (n = 19) received CoQ(10) orally at doses of 300 mg/day for 1 month, whereas the other group received a placebo. On entry and after 1 month, all patients underwent brachial artery ED assessment, cardiopulmonary exercise test, and the measurement of endothelium-bound ecSOD activity. A total of 33 patients completed the study. ecSOD, ED relaxation, as well as peak VO(2) and O(2) pulse increases in the CoQ(10)-treated group were statistically greater vs. the variations in the placebo group. In particular, improvements elicited by CoQ(10) supplementation were remarkable in subjects presenting low initial endothelium-bound ecSOD and thus more prone to oxidative stress. CONCLUSION: Improvements in the ED relaxation and endothelium-bound ecSOD activity might be related to CoQ(10) capability of enhancing endothelial functionality by counteracting nitric oxide oxidation. The enhancement of peak VO(2) and of O(2) pulse is likely due to the bioenergetic effect of CoQ(10); on the other end, the improved VO(2) could also depend on the observed enhanced peripheral endothelial function.     

AMPK基因在C57BL／6J小鼠糖脂代谢中的作用

目的研究腺苷酸活化蛋白激酶（AMPK）基因在C57BL／6J小鼠糖脂代谢中的作用。方法分别取5周龄AMPK基因敲除（AMPK-KO）小鼠和C57BL／6J对照小鼠各24只,分为正常饲料（ND）喂养和高脂高糖饲料（HFD）喂养两组。喂养12周,每两周测定小鼠禁食4h血糖（FBG）,实验结束前行口服糖耐量实验（OGTT）,解剖取样,检测血生化指标、脂酶活性及相关蛋白的表达。结果AMPK-KO小鼠血糖、TC、LDL-C、HbA1c、6-磷酸葡萄糖脱氢酶（G6PD）活性、糖原合成酶激酶（GSK）活性、肝脏PPAR7蛋白表达量明显高于对照小鼠（P〈0．05）;其胰岛素含量、肝糖原含量、肌糖原含量、肝脂酶（HL）活性、脂蛋白酯酶（LPL）活性、总脂酶活性、葡萄糖激酶（GK）活性、肝组织P-AMPK蛋白、葡萄糖转运蛋白4（GluT-4）蛋白的表达量低于对照组（P〈0．05）。结论AMPK基因通过调节C57BL／6J小鼠糖脂代谢,在T2DM的发病中起重要作用。     

Study of Biofilm Formation in C57Bl/6J Mice by Clinical Isolates of Helicobacter pylori

Background/Aim:

Despite the significant number of studies on H. pylori pathogenesis, not much data has been published concerning its ability to form biofilm in the host stomach. This study aims to evaluate the potential of clinical isolates of H. pylori to form biofilm in C57BL/6J mice model.

Materials and Methods:

Two strains of H. pylori were selected from a collection of clinical isolates; one (19B), an efficient biofilm producer and the other (4B), with weak biofilm-forming ability. Mice infected through gastric avages were examined after one and two weeks. Colonization was determined by CFU and urease activity; the anti-H. pylori IgA was measured by ELISA, and chronic infections were evaluated by histopathology. Bacterial communities within mucosal sections were studied by immunofluorescence and scanning electron microscopy (SEM).

Results:

Successful infection was obtained by both test strains. Strain 19B with higher ability to form biofilm in vitro also showed a higher colonization rate in the mice stomach one week after infection. Difference (P < 0.05) in IgA titers was observed between the infected mice and the controls as well as between 19B and 4B infected mice, two weeks after the last challenge. Immunofluorescence and SEM results showed tightly colonizing H. pylori in stomach mucosal sections and in squamous and glandular epithelium.

Conclusion:

H. pylori is able to form biofilm in the mouse stomach and induce IgA production, reflecting the same potential as in humans. Firm attachment of coccoid form bacteria to host cells suggests the importance of this state in biofilm formation by H. pylori. Occurrence of biofilm in squamous and glandular epithelium of the mouse stomach proposes that H. pylori can all parts of the upper gastrointestinal tract.     

链脲菌素剂量对C57BL/6J小鼠糖尿病诱导效应的影响

目的 观察不同剂量链脲菌素(STZ)对C57BL/6J小鼠糖尿病诱导效应的影响,探讨其量效关系及最佳剂量范围.方法 将C57BL/6J小鼠按数字随机法分为9个STZ剂量组(A～I组,STZ分别为30、60、80、100、120、150、180、210、240 ms/kg体重),每组15只,腹腔注射;1个对照组,10只,腹腔注射等体积缓冲液.观察各组血糖、体重、血胰岛素和45 d生存率的变化,分析其与STZ剂量的关系.同时取A、C、G及对照组小鼠胰腺、肾脏组织做病理学检杏,并行免疫组化观察胰腺胰岛素及肾脏CD<,68>的表达.结果 C～G组较对照组血糖增高、体重及血胰岛素含量较对照组下降非常显著(P<0.05),且STZ剂量与血糖呈正相关(r=0.984,P<0.05),与血胰岛素含量呈负相关(r=-0.994,P<0.05).C～G组成模率达86.7%～100%,显著高于A、B组的0和40%(P<0.05);45 d生存率为46.7%～73.3%,显著高于H、I组的13.3%和0(P<0.05).A组胰腺、肾脏组织未见明显破坏;C组及G组出现典型的胰岛萎缩变形,胰岛素分泌颗粒减少,肾小球系膜外基质沉着及球周臣噬细胞浸润.结论 C57BL/6J小鼠腹腔注射STZ以80～180 mg/kg体重的剂量制模率高、生存率高,且靶器官损伤典型;该剂量与血糖呈正相关,与血胰岛素含量呈负相关.     

Acute Functional Tolerance to Ethanol and Fear Conditioning Are Genetically Correlated in Mice

It has been speculated that tolerance to alcohol involves some form of neuronal plasticity that is similar to or the same as that mediating learning and memory. To investigate this possibility further, we tested the hypothesis that acute functional tolerance (AFT) to alcohol is genetically correlated to a Pavlovian learning task fear conditioning. Mice selectively bred for differences in ability to acquire AFT were tested for fear conditioning. Subjects received a mild footshock paired to a broadband clicker and were tested 24 hr later for their freezing response to the conditioning chamber (context), to an altered chamber, and to the clicker. Both the original and replicate lines selected for high AFT (HAFT) were found to freeze significantly more than those selected for low AFT (HAFT) in response to the context and to the clicker. In a second experiment, an F₂ Population derived from the C57BL/6 (B6) and DBA/2 (D2) mouse strains were tested first for fear conditioning, followed 3 weeks later by AFT testing. AFT was defined as the difference between blood alcohol levels determined at the time of regain balance on a dowel rod first after 1.75 g/kg of ethanol and again after a subsequent dose of 2.0 g/kg. Consistent with results from HAFT and LAFT, freezing to context was found to be significantly positively correlated to AFT ( r = 0.38, p = 0.04) in the F₂ mice. The results suggest that co-variation in fear conditioning and AFT may be mediated by one or more of the Same or at least tightly linked genes. Further dissection of this correlation may reveal neuronal mechanisms common to both AFT and fear conditioning.     

Naltrexone Effects on Ethanol Drinking Acquisition and on Established Ethanol Consumption in C57BL/6J Mice

Naltrexone's success as a treatment agent for alcoholism seems to be due to its ability to reduce craving in abstinent, dependent individuals and to reduce the pleasure associated with subsequent intake. However, more study is needed to establish the optimal amount of time that naltrexone treatment should be continued. Little information seems to have been collected regarding the most effective dosing regimen for reducing alcohol craving and consumption, and the usefulness of opiate antagonists in the prevention of alcohol dependence in nonaddicts, rather than just as a treatment agent in addicted individuals, also deserves further study. The alcohol-preferring C57BL/6J (B6) mice were used to: (1) study naltrexone effects on consumption in established drinkers using an increasing dosing regimen, (2) study naltrexone effects on the acquisition of ethanol drinking, and (3) study the effects of chronic naltrexone from timed-release pellets on drinking in alcohol-naive mice. Naltrexone reduced ethanol preference in established drinkers, but its effects waned at increasing doses. Naltrexone slowed the acquisition of ethanol drinking, but was ineffective when readministered after a phase when ethanol was offered in the absence of naltrexone. Mice with chronic naltrexone pellets consumed greater amounts of ethanol and showed higher ethanol preference than did placebo-pelleted animals. The observed reduced efficacy of naltrexone with increasing dosage and chronic treatment may have been due to naltrexone-induced opiate receptor changes. Such changes are presumably more likely to occur when naltrexone doses remain high or perhaps accumulate. Thus, dose and frequency of administration may be important factors in determining naltrexone's effectiveness in treating alcohol dependence.     

Bipedal ambulation induces experimental scoliosis in C57BL/6J mice with reduced plasma and pineal melatonin levels

In addition to the induction of scoliosis in chickens by pinealectomy (PINX), we previously demonstrated that removal of the pineal gland also produces scoliosis in bipedal rats, which can be inhibited by melatonin treatment. Using C57BL/6J mice with genetically low circulating melatonin levels, the main objective of the present study was to investigate whether bipedal ambulation in C57BL/6J mice has the same effects on spinal deformity as those seen in pinealectomized bipedal rats. The present study consisted of two phases. The aim of the first experiment was to determine whether the C57BL/6J mouse strain actually exhibits depressed plasma concentrations and/or pineal contents of melatonin during both the light and the dark phase of the light:dark cycle. The aims of the second experiment were to evaluate; (i) whether bipedal ambulation alone in the C57BL/6J mouse induces scoliosis, and (ii) whether PINX with bipedal ambulation in another mouse strain, i.e. C3H/HeJ, which normally exhibits diurnal fluctuations in melatonin synthesis and secretion, has effects similar to those of bipedal ambulation alone in C57BL/6J mice. C3H/HeJ mice, serving as controls, showed significant increases in both plasma concentrations and pineal contents of melatonin during the dark phase when compared with the light phase. In contrast, there were no differences in either circulating levels or pineal contents of melatonin between the light and dark phases in C57BL/6J mice. Moreover, plasma melatonin levels were below the detection limit of the assay in both phases and pineal melatonin was < 10% of that in C3H/HeJ mice. Bipedal ambulation for 40 wk in C57BL/6J mice induced scoliosis at a rate of 64.3%, and two of nine scoliotic mice showed two sites of spinal deformity. This type of ambulation in C3H/HeJ mice resulted in scoliosis at a lower rate (25%), and affected animals had only a single scoliotic site. However, PINX combined with bipedal ambulation in C3H/HeJ mice produced scoliosis at a rate (70%) similar to that seen in C57BL/6J mice, and some double deformations were induced. These results confirm our previous observations in rats, and also support our hypothesis that melatonin as well as the bipedal ambulation appear to play a critical pathogenic role in scoliosis in experimental mammals.     

Cellular coenzyme Q10 redox poise constitutes a major cell metabolic and gene regulatory system

A hypothesis as to the nature of the ageing process is presented. Our studies lead us to emphasise that ageing is a stochastic process; it is individualistic, it is species specific, it is different for individuals within a species, it is organ and tissue specific as well as varying among individual cells of a tissue. Human ageing is a slow process which takes place over decades; it is a cellular process in a dynamic equilibrium of continuing damage and repair. Tissues are damage mosaics. We hypothesise that the characteristic of ageing post-mitotic tissues is the progressive, slow loss of cells; those cells which no longer adequately function are removed by an apoptotic or non-inflammatory necrotic process. A case is made for an encompassing role for coenzyme Q₁₀ in the regulation of systemic disease, cellular metabolism and ageing. This revised version was published online in July 2006 with corrections to the Cover Date.     

Randomised double-blind, placebo-controlled trial of coenzyme Q, therapy in class II and III systolic heart failure

BACKGROUND: Coenzyme Q10 (CoQ10) supplementation has been reported to improve symptoms of heart failure and quality of life, and to reduce hospitalisation. Most prior trials have been open-label and in some, only 50% of patients took angiotensin converting enzyme inhibitors (ACEI). AIM: To determine the effects of CoQ10 in patients with a New York Heart Association (NYHA) Class II or III heart failure due to ischaemic or dilated cardiomyopathy who have been treated with ACEI but not beta-blockers. Methods: Thirty-nine patients in NYHA Class II or III heart failure were randomised in ad ouble-blind, placebo-controlled study with 150 mg/day of oral CoQ10 or placebo.RESULTS: Thirty-five patients completed the trial. After 3 months of therapy, the NYHA class in the CoQ10 group (n = 17) showed a significant improvement of 0.5 class compared with the placebo (n = 18) (P = 0.01). Specific Activities Scale class showed a significant (P = 0.004) improvement in the CoQ10 group, but no change in the placebo group. The C-min walk-test distance showed a significant (P = 0.047) increase in the CoQ10 group with no change in the placebo group (between-group difference P = 0.29). For the Naughton exercise test times the difference in increase in exercise time approached significance in favour of the CoQ10 group (P = 0.056). There was a correlation between the increase in exercise time and the increase in serum CoQ10 level (P = 0.024). There was a threefold increase in the CoQ10 level in the treated group (0.7 +/- 0.4 to 2.1+/- 0.3 microg/mL), but no change in the placebo group. CONCLUSIONS: This pilot study accords with published data suggesting that CoQ10 therapy improves cardiac functional status in patients with moderately severe dilated cardiomyopathy receiving maximal non beta-blocker therapy. Future multicentre studies with larger numbers are indicated.     

Inflammation and mortality in a frail mouse model

Mice homozygous for targeted deletion of the interleukin 10 gene (Il-10) have been partially characterized as a model for human frailty. These mice have increased serum interleukin (IL)-6 in midlife, skeletal muscle weakness, and an altered skeletal muscle gene expression profile compared to age and sex-matched C57BL/6 (B6) control mice. In order to further characterize for use as a frailty model, we evaluated the evolution of inflammatory pathway activation, endocrine change, and mortality in these mice. Serum was collected in groups of age- and sex-matched B6.129P2-Il10 ^tm1Cgn /J (IL-10^tm/tm) mice and B6 control mice at age 12, 24, 48, 72, and 90 weeks. Cytokines including IL-6, interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), chemokine (C-X-C motif) ligand 1 (KC), IL-12, and IL-10 were measured using electro-chemiluminescent multiplex immunoassay and insulin-like growth factor 1 (IGF-1) was measured using solid-phase enzyme-linked immunosorbent assay. A separate longitudinal cohort was monitored from age 35 weeks to approximately 100 weeks. Survival was evaluated by Kaplan–Meier survival estimates and detailed necropsy information was gathered in a subset of mice that died or were sacrificed. In IL-10^tm/tm mice compared to B6 controls, serum IL-6, IL-1β, TNF-α, IFN-γ, KC levels were significantly elevated across the age groups, serum mean IGF-1 levels were higher in the 48-week-old groups, and overall mortality rate was significantly higher. The quadratic relationship between IGF-1 and age was significantly different between the two strains of mice. Serum IL-6 was positively associated with IGF-1 but the effect was significantly larger in IL-10^tm/tm mice. These findings provide additional rationale for the use of the IL-10^tm/tm mouse as a model for frailty and for low-grade inflammatory pathway activation.     

Period determination in the food-entrainable and methamphetamine-sensitive circadian oscillator(s)

Daily rhythmic processes are coordinated by circadian clocks, which are present in numerous central and peripheral tissues. In mammals, two circadian clocks, the food-entrainable oscillator (FEO) and methamphetamine-sensitive circadian oscillator (MASCO), are "black box" mysteries because their anatomical loci are unknown and their outputs are not expressed under normal physiological conditions. In the current study, the investigation of the timekeeping mechanisms of the FEO and MASCO in mice with disruption of all three paralogs of the canonical clock gene, Period, revealed unique and convergent findings. We found that both the MASCO and FEO in Per1(-/-)/Per2(-/-)/Per3(-/-) mice are circadian oscillators with unusually short (～21 h) periods. These data demonstrate that the canonical Period genes are involved in period determination in the FEO and MASCO, and computational modeling supports the hypothesis that the FEO and MASCO use the same timekeeping mechanism or are the same circadian oscillator. Finally, these studies identify Per1(-/-)/Per2(-/-)/Per3(-/-) mice as a unique tool critical to the search for the elusive anatomical location(s) of the FEO and MASCO.     

Melatonin reduces cholesterol accumulation and prooxidant state induced by high cholesterol diet in the plasma, the liver and probably in the aorta of C57BL/6J mice

We examined the hypolipidemic and antioxidative effects of melatonin in plasma, liver and aorta of C57BL/6J mice fed on a high cholesterol (HC) diet. Mice were fed normal mice chow containing 1.5% cholesterol and 0.5% cholic acid for 4 months with or without melatonin (10 mg/L in drinking water) treatment. HC diet was observed to increase cholesterol, triglyceride and diene conjugate (DC) levels in plasma and liver. There was a tendency towards an increase in cholesterol level in the aorta following HC diet. In addition, aortic DC levels were higher than those of control group. No fatty streaks or plaques developed in the aorta of mice following HC diet, but in some sections, derangement of the endothelial layer was detected. Melatonin treatment was found to reduce plasma, liver cholesterol and DC levels as well as liver triglyceride levels in hypercholesterolemic mice. Aortic cholesterol and DC levels were also reduced in hypercholesterolemic mice when given melatonin, although not statistically significant. There were no differences in aortic histopathological findings of mice fed on a HC diet with and without melatonin treatment. In conclusion, our results indicate that melatonin reduces HC diet-induced cholesterol accumulation and prooxidant state in the plasma, liver and probably in the aorta.     

Restoration of the behavioral rates and lifespan in clk-1 mutant nematodes in response to exogenous coenzyme Q(10)

The clk-1 gene encodes demethoxyubiquinone mono-oxygenase that is necessary for the biosynthesis of coenzyme Q (CoQ), which is an electron transporter in the respiratory chain of mitochondria. Therefore, clk-1 mutant nematodes that have loss-of-function mutations in the clk-1 gene lack endogenous CoQ(9) and exhibit slowed behavioral rates and an extended lifespan compared with wild-type animals when they are fed standard bacteria containing endogenous CoQ(8). This finding suggests that clk-1 regulates behavioral rates and the lifespan through CoQ in nematodes; however, the effects of exogenous CoQ on the regulation of these biological processes have been incompletely evaluated. In this study, we found that adding 10 μM water-soluble CoQ(10) to the culture medium of clk-1 mutant nematodes that were fed a diet of standard bacteria restored the pharyngeal pumping, defecation and the lifespan to levels that were comparable to those of wild-type animals. The results indicate that both behavioral rates and lifespan are regulated by the clk-1 gene through the action of CoQ in nematodes.