Emodin and aloe-emodin, two potential molecules in regulating cell migration of skin cells through the MAP kinase pathway and affecting Caenorhabditis elegans thermotolerance.

BACKGROUND: Emodin and aloe-emodin are two anthraquinones having positive effects in wound healing. However, their mechanism of action of wound healing is not fully understood. The MAP kinase family, which plays an active role in wound healing, is a well-characterized large family of serine/threonine kinases and regulates processes such as proliferation, oncogenesis, differentiation, and inflammation in the cell. The aim of this study is to comparatively elucidate the mechanisms of action of emodin and aloe-emodin, which are potential agents in wound healing. METHODS: The mechanism of the effects of emodin and aloe-emodin on cell viability and cell migration was examined using the human skin fibroblast (CCD-1079Sk) cell line. The gene expression levels of the MAP kinases (JNK, P38, ERK) in the skin fibroblast cells along with a molecular docking study analyzing their interaction potential were evaluated. Furthermore, the molecules' effects on the lifespan of Caenorhabditis elegans were studied. RESULTS: Emodin and aloe-emodin inhibited the ATP content of the cells in a concentration dependent manner and accelerated cell migration at the lower concentrations while inhibiting cell migration in the higher concentration treatment groups. The expressions of JNK and P38 were upregulated at the low concentrations and downregulated at the higher concentrations. The molecular docking studies of the molecules gave high docking scores indicating their interaction potential with JNK and P38. C. elegans lifespan under heat stress was observed longer after 75 µM emodin and was significantly reduced after 150 µM aloe-emodin treatment. CONCLUSION: Aloe-emodin was found to be more potent on cell viability, cell migration, gene expression levels of the MAP kinases in healthy fibroblastic skin cells, and on the lifespan of C. elegans. This study reveals the functional effects and the biological factors that interact in the wound healing process of emodin and aloe-emodin, and give a possible treatment alternative to shorten the duration of wound care.

Selective targeting of signet ring cell adenocarcinomas.

Many epithelial tumors, especially signet-ring cell adenocarcinomas, produce huge amounts of mucin glycoproteins that fill cytoplasm and push nucleus to the periphery, giving a signet ring like structure to the cell. Mucin proteins are very rich of l-threonine which is essential in humans. L-threonine content can reach up to 35% of total amino acid composition of some mucin proteins. Therefore l-threonine can be the Achilles heel of signet ring cell adenocarcinomas which are one of the most malignant and agressive cancers. A modified bioisoster of l-threonine, 4-fluoro l-threonine (its fluorine can be radioactive or not), can be used to selectively kill signet ring cancer cells without harming normal cells or for diagnostic purposes.

"Metformin-resistant" folic acid producing probiotics or folic acid against metformin's adverse effects like diarrhea.

Metformin, first line medication in the treatment of type2 diabetes by millions of patients worldwide, causes gastrointestinal adverse effects (i.e. diarrhea) in approximately 30% of patients, frequently leading to discontinuation. Interestingly, metformin was reported to increase life span in a microscopic worm, Caenorhabditis elegans, by decreasing folate and methionine production of bacteria that this worm uses as a food source. Metformin can be expected to have a similar effect on some microorganisms of human gut microbiota. This can disturb the balance of gut microbiota and cause gastrointestinal adverse effects by altering folate production of some types of bacteria and suppress their growth. Metformin resistant probiotics can be discovered or generated by artificial evolution/selection, and used to prevent these adverse effects. These patients can also be managed with folate supplementation.

Possible Effects of Copper and Ceruloplasmin Levels on Auditory Event Potentials in Boys with Attention Deficit Hyperactivity Disorder.

INTRODUCTION: The aims of the present study were to investigate the relationship between levels of plasma copper (Cu) and ceruloplasmin (Cp) and amplitudes and latencies of P1, N2, and P3 in the parietal and frontal areas of children with attention deficit hyperactivity disorder (ADHD) as well as to compare these Cu levels and event-related potentials (ERPs) indices in controls. METHODS: Boys (n=41) with ADHD were divided into two subgroups according to a median split of plasma Cu and Cp levels, separately. ERP indices from the parietal and frontal regions were recorded in children with ADHD and 24 normal boys (control group) using an auditory oddball paradigm. RESULTS: Parietal P3 latency was significantly longer, and parietal P3 amplitude, frontal P3 amplitude, and frontal N2 amplitudes were smaller in children with ADHD than in controls (all p values <0.017). Parietal P1 and frontal P1 latencies were significantly shorter in the higher Cu group than in the lower Cu group (both p values <0.017). Decreased latency of parietal P1 was dependent on plasma levels of Cu (p<0.05). Frontal N2 and parietal N2 amplitudes were significantly lower in the ADHD group with lower Cp levels than in the ADHD group with higher Cp levels (both p values <0.017). Decreased frontal N2 and parietal N2 amplitudes were dependent on plasma levels of Cp (both p values <0.05). CONCLUSION: Plasma Cu and Cp levels may have an effect on ERPs in ADHD, thus indicating the existence of effects on information processing. Cu levels may have a negative effect on the neuronal encoding of sound, whereas Cp levels may have a positive effect on the processes of cognitive control, conflict monitoring, and stimulus discrimination in children with ADHD.

The effect of nonsurgical periodontal treatment on serum and saliva chitotriosidase activities in patients with periodontitis and coronary artery disease.

BACKGROUND: Plasma chitotriosidase activity, which is a marker of macrophage activation, has been reported to increase in inflammatory conditions and atherosclerosis. Chronic periodontitis has likely an important role in the development of coronary artery disease. In this study, we aimed to analyze the effect of chronic periodontitis on salivary and plasma chitotriosidase activities in patients with or without coronary atherosclerosis. METHODS: Fifty subjects were divided into four groups as controls (n=13), periodontitis (n=11), coronary artery disease (n=13), and periodontitis + coronary artery disease (n=13). Plasma and saliva chitotriosidase activities were measured by a fluorimetric method in all groups before the nonsurgical treatment of periodontitis and 5 weeks posttreatment in periodontitis groups. RESULTS: Salivary chitotriosidase activity was decreased after nonsurgical periodontal treatment in patients having periodontitis with or without coronary atherosclerosis. However, plasma activities remained unchanged. CONCLUSION: Although this study has some limitations like small sample size and short study duration, it can suggest that salivary chitotriosidase can have the potential to be used as a very useful and practical marker to evaluate the success of the periodontal treatment and/or host response. KEY FINDING: Salivary chitotriosidase can be used as a marker for the evaluation of the success of the periodontal treatment and/or host response.

Assessing leptin and soluble leptin receptor levels in full-term asymmetric small for gestational age and healthy neonates.

The aim in this study was to determine the factors affecting leptin and soluble leptin receptor (sOB-R) levels in term small for gestational age (SGA) and appropriate for gestational age (AGA) newborns. The study group consisted of SGA (n=20) and AGA (n=20) newborns and their mothers. The leptin and sOB-R levels were tested using the ELISA method. The cord blood leptin concentrations were found significantly higher in the AGA group than in the SGA group (p=0.048). It was observed that cord blood leptin levels increased as body weight increased in the AGA group (r=0.681, p=0.001). The cord blood leptin levels were found higher in female infants than male infants (p=0.021). The plasma leptin levels were higher in the mothers of SGA neonates than those of AGA neonates (p=0.014). A positive correlation was detected between cord blood and amniotic fluid sOB-R concentrations in the AGA group (AGA: r=0.492, p=0.028). We conclude that the main determinants of leptin in SGA and AGA newborns are different. We can state that birth weight and gender are the main determinants of leptin levels in healthy neonates, but factors other than birth weight and gender may contribute to leptin levels in SGA newborns.

Serum chitotriosidase activity: is it a new inflammatory marker in obese children?

Chitotriosidase (ChT) is an enzyme secreted by activated macrophages and involved in defense against, and in degradation of chitin-containing pathogens, such as fungi, nematodes, and insects. In addition, it plays an important role in the development of atherosclerosis related with systemic low-grade inflammation. To this effect of activity of ChT, we aimed to investigate serum ChT activity in obese subjects and to determine to relation with insulin resistance and high-sensitive C-reactive protein (hsCRP). A total of 73 obese subjects (10.9 +/- 2.6 years of age, 44 male patients) and 41 age and gender-matched healthy lean subjects (11.6 +/- 2.9 years of age, 18 male patients) were included in this study, between 2007 and 2008. The criterion for diagnosing obesity was defined as the body mass index (BMI) being over 97th percentile of the same gender and age. Fasting serum glucose, insulin, hsCRP and ChT levels were measured. We compared the differences in variables between obese and lean subjects with Student's t-test compared after ascertaining that the data were normally distributed. All data were expressed as mean +/- standard deviation. There was statistically significant increase in serum ChT activity of obese subjects, while there was statistically significant difference in serum hsCRP levels when compared to healthy lean subjects (30.0 +/- 17.9 and 23.0 +/- 17.8, p=0.045; 2.3 +/- 3.1 and 0.7 +/- 1.2, p=0.001). Obese subjects had significantly higher BMI-SDS, TG and HOMA-IR and lower HDL-C levels when compared with the healthy lean subjects (p<0.05). Correlation analysis showed no significant correlation between serum ChT activity and hsCRP, HOMA-IR and BMI-SDS (p>0.05). Although the data need to be validated by further investigation, the observations made in this study seem to indicate that serum ChT activity may not be a useful marker for monitoring systemic low-grade inflammation and insulin resistance in obese subjects.

Converting NADH to NAD+ by nicotinamide nucleotide transhydrogenase as a novel strategy against mitochondrial pathologies during aging.

Mitochondrial DNA defects are involved supposedly via free radicals in many pathologies including aging and cancer. But, interestingly, free radical production was not found increased in prematurely aging mice having higher mutation rate in mtDNA. Therefore, some other mechanisms like the increase of mitochondrial NADH/NAD(+) and ubiquinol/ubiquinone ratios, can be in action in respiratory chain defects. NADH/NAD(+) ratio can be normalized by the activation or overexpression of nicotinamide nucleotide transhydrogenase (NNT), a mitochondrial enzyme catalyzing the following very important reaction: NADH + NADP(+ )<--> NADPH + NAD(+). The products NAD(+) and NADPH are required in many critical biological processes, e.g., NAD(+) is used by histone deacetylase Sir2 which regulates longevity in different species. NADPH is used in a number of biosynthesis reactions (e.g., reduced glutathione synthesis), and processes like apoptosis. Increased ubiquinol/ubiquinone ratio interferes the function of dihydroorotate dehydrogenase, the only mitochondrial enzyme involved in ubiquinone mediated de novo pyrimidine synthesis. Uridine and its prodrug triacetyluridine are used to compensate pyrimidine deficiency but their bioavailability is limited. Therefore, the normalization of the ubiquinol/ubiquinone ratio can be accomplished by allotopic expression of alternative oxidase, a mitochondrial ubiquinol oxidase which converts ubiquinol to ubiquinone.

Potential effects of zinc on information processing in boys with attention deficit hyperactivity disorder.

PURPOSE: The aims of the present study were to investigate the relationship between plasma zinc levels and amplitudes and latencies of P1, N2, and P3 in parietal and frontal areas in children with ADHD, and to compare these zinc levels and event-related potentials (ERPs) indices with controls. METHODS: 28 boys with ADHD were divided into two groups according to plasma zinc levels: low zinc group (N=13, zinc level <80 microg/dL) and zinc non-deficient group (N=15, zinc level >or=80 microg/dL). ERP indices from parietal and frontal brain regions were recorded in children with ADHD and in 24 normal boys by using an auditory oddball paradigm. Plasma zinc levels were measured by an atomic absorption spectrophotometer. RESULTS: The plasma zinc levels were significantly lower in both ADHD groups (means are 65.8 microg/dL in low zinc group and 89.5 microg/dL in zinc non-deficient group) than controls (mean: 107.8 microg/dL; both p values <0.017). In ADHD compared to controls, the amplitudes of P3 in frontal and parietal regions were significantly lower, and the latency of P3 in parietal region was significantly longer (all p values <0.017). In low zinc ADHD group compared to zinc non-deficient ADHD group, the latencies of N2 in frontal and parietal region were significantly shorter (all p values <0.017). In addition, there was a medium but significant positive correlation between plasma zinc levels and amplitude and latency of frontal N2 wave in ADHD. CONCLUSIONS: These results can suggest that plasma zinc levels might have an effect on information processing in ADHD children, and lower zinc levels seem to affect N2 wave. Since N2 wave changes may reflect a different inhibition process, further studies are warranted to investigate the effect of zinc on inhibitory process in children with ADHD, and in low zinc and non-deficient ADHD groups.

Effect of testosterone on insulin sensitivity in men with idiopathic hypogonadotropic hypogonadism.

OBJECTIVE: To assess the presence of insulin resistance (IR) among a homogeneous cohort of male patients with idiopathic hypogonadotropic hypogonadism (IHH) and to investigate the effects of testosterone therapy on IR in this specific group. METHODS: Twenty-four male patients with untreated IHH and 20 age-, sex-, and weight-matched eugonadal healthy control subjects were recruited for the study. Plasma glucose, plasma insulin, total and free testosterone, follicle-stimulating hormone, luteinizing hormone, estradiol, and sex hormone-binding globulin levels were measured in fasting blood samples, and biochemical and hormonal analyses were performed for all study participants. IR was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula and the quantitative insulin sensitivity check index (QUICKI). Body mass index was calculated by weighing and measuring the heights of all study participants at the beginning of the investigation. Body fat mass and body lean mass were calculated as percentages of body weight by bioelectrical impedance analysis of body composition. Sustanon 250 (a combination of 4 testosterones) was administered intramuscularly once every 3 weeks for 6 months to male patients with IHH after a basal anthropometric, biochemical, and hormonal evaluation. The response to therapy was monitored by regular clinical examinations and serum testosterone measurements. After 6 months of testosterone treatment, the entire anthropometric, biochemical, and hormonal evaluation was repeated 14 days after the last injection of testosterone. RESULTS: Before treatment, male patients with IHH had higher fasting plasma glucose concentrations, higher fasting plasma insulin levels, a higher HOMA-IR score, and a lower QUICKI when compared with the control group. After testosterone treatment in the patient group, the HOMA-IR score decreased dramatically to the level in the control group. The high body fat mass of the male patients with IHH was reduced significantly after testosterone treatment, concomitant with significant increases in body mass index and body lean mass. CONCLUSION: Insulin sensitivity improves and body fat mass decreases with long-term testosterone replacement therapy.

Chitotriosidase levels in healthy elderly subjects.

Chitotriosidase (CHIT) belongs to the family of glycosylhydrolases and is highly homologous to chitinases from lower organisms. The enzyme CHIT is of interest for clinical reasons, because it is selectively expressed in chronically activated tissue macrophages. In most ethnic groups, approximately 6% of all individuals are homozygous for CHIT deficiency. Pathological tissue macrophages in several disease conditions massively express CHIT. A shared feature of such cells in the different conditions is the accumulation of lipid material in the lysosomal apparatus. Serum CHIT activity is significantly increased in individuals suffering from atherosclerosis disease and is related to the severity of the atherosclerotic lesion, suggesting a possible role as atherosclerotic extent marker. Our objective is to determine the levels of serum CHIT activity in healthy elderly subjects. Healthy 90 (between 65-94 years old) elderly people and 69 (between 20-44 years old) young people were chosen. Serum CHIT enzymatic activity was determined with the flurometric enzyme activity assay using artificial 4-MU substrate. We found CHIT activity 270 +/- 21 (nmol/mL/h) (values are mean +/- SD) in elderly people and 136 +/- 17 in young people. There are statistical differences between elderly and young subjects.

Age-related paraoxonase activity changes in Turkish population.

Paraoxonase1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme capable of hydrolyzing diverse substrates from organophosphate (OP) toxins to oxidized phospholipids. As such, it has been linked with both the prevention of OP poisoning and inhibition of atherosclerosis initiated by oxidatively modified low-density lipoprotein (LDL). The aim of this study was to investigate, with aging, the activity of PON1 associated with HDL and partially responsible for its antiatherogenic activity. The study involved 187 individuals (67 males and 120 females) divided into three groups according to their ages, young (n = 49; 20-44 years, mean age = 30.12 +/- 6.6 years), middle aged (n = 25; 45-64 years, mean age = 52 +/- 5.6 years), and elderly subjects (n = 113; 65-95 years, mean age = 78.94 +/- 6.2 years). Interestingly, serum total cholesterol and LDL-cholesterol levels significantly decreased with age (P < 0.05). The elderly aged group had also significantly lower body mass index than the middle aged group (P < 0.05). Serum paraoxonase activity and HDL cholesterol levels remained unchanged with age. The prevalence of phenotype AA, AB, and BB in our subjects' group was 40.6%, 45.9%, and 13.5%, respectively.

Mitochondrial DNA-deficient models and aging.

Human mitochondrial DNA (mtDNA) encodes 13 subunits of oxidative phosphorylation (OXPHOS) enzyme complexes I, III, IV, and V except complex II. MtDNA is more sensitive to oxidative damage than nuclear DNA. MtDNA defects are involved in many pathologies including aging. Several mtDNA-deficient cell culture, yeast, and animal models were generated to study the role of mtDNA in many physiological processes. Ethidium bromide (EB), an agent that is known to inhibit mtDNA replication with a negligible effect on nuclear DNA, is generally used to generate mtDNA-deficient models. The antibiotics chloramphenicol and doxycycline, which were known to inhibit mitochondrial translation, were also used to generate the same phenotype. Cultured mtDNA-deficient cells need uridine and pyruvate to survive. At the organismal level, uridine can be supplemented, but pyruvate supplementation can cause a worser phenotype because of lactic acidosis. In C. elegans, EB, when used during larval development, increases life span, but decreases, when used after the beginning of adult stage. This should be kept in mind since mitochondria-related genes are generally detected in genome-wide screening studies for longevity. We believe that conditional knockout studies need to be carried out for these genes after reaching adulthood. MtDNA mutator mouse did not show an increase of free radical production. Therefore, the downstream phenomena to mtDNA defects are likely ineffective pyrimidine synthesis (dihydroorotate dehydrogenase, DHODH, needs a functional respiratory chain) and excess NADH (decreased NAD pool) in addition to free radicals.

Mitochondrial DNA alterations in aging.

During the aging process, the increase of mitochondrial DNA (mtDNA) alterations has been reported. In this study, we investigated deletions/insertions in the approximately 2.4-kb region (from 14680 to 578 bp) of mtDNA covering D-loop region. A total of 96 individuals (ages between 20 and 94 years) were screened in this study. Genomic DNA was purified from whole blood samples. The 2.4-kb region of mtDNA was amplified with PCR and visualized by agarose gel electrophoresis. The sequence of the amplicon was confirmed in one sample by sequencing. We detected mtDNA deletions in only two cases (ages 26 and 30 years) at this resolution. As a result, there is no increase in the major deletions/insertions in the analyzed mtDNA region with aging. Complete sequencing of this region is needed to detect any age-dependent changes.

Deuteronation and aging.

Deuterium has one proton and one neutron in its atomic nucleus, but hydrogen has only proton. The natural abundance of deuterium is 1 per approximately 6600 hydrogen atoms. Therefore deuterated water (both HOD + D(2)O [heavy water]) abundance is 1 per approximately 3300 water molecules. One dissociation product of deuterated and heavy water is deuteron (proton + neutron, D(+), H(2)OD(+)/D(3)O(+)). Because heavy water has a lower ionization constant than water, the D(+)/H(+) ratio is approximately 1/15,000 in biological fluids. O-D bond length is shorter than O-H, and D-O-D angle is lesser than H-O-H. Once a deuteron exchanges with proton on the water-exposed surface of a macromolecule, it can lead to a conformational change and the reverse exchange will be less likely. Deuteron bonds are stronger than proton bonds. Therefore an increase of deuteronated macromolecules can be expected in due course of time. In order to test this hypothesis, we conducted a pilot study and measured the D/H ratio in the tails of three Sprague-Dawley rats at different ages (4 weeks, 5 weeks, and >1-year old) by elemental analysis coupled with isotope ratio mass spectrometry (EA-IRMS) technique. To prevent the effect of daily water consumption, the homogenized tails were lyophilized before analysis. The results, as mean of several measurements, of 4 weeks, 5 weeks, and >1-year-old rats were per thousand-94 +/- 9.56, per thousand-101.71 +/- 6.89, per thousand-83.68 +/- 3.46 delta((2)H) relative to VSMOW, respectively. Although there is a slight increase in >1-year-old rat, the difference among the animals was not significant. We propose that, before reaching to a final conclusion about the accumulation of deuterium with aging, the measurements should be done not in whole tissue samples but in purified macromolecules from a larger set of animals.

Biological effects of deuteronation: ATP synthase as an example.

BACKGROUND: In nature, deuterium/hydrogen ratio is approximately 1/6600, therefore one of approximately 3300 water (H2O) molecules is deuterated (HOD + D2O). In body fluids the ratio of deuterons to protons is approximately 1/15000 because of the lower ionization constant of heavy water. The probability of deuteronation rather than protonation of Asp 61 on the subunit c of F0 part of ATP synthase is also approximately 1/15000. The contribution of deuteronation to the pKa of Asp 61 is 0.35. THEORY AND DISCUSSION: In mitochondria, the release of a deuteron into the matrix side half-channel of F0 is likely to be slower than that of a proton. As another example, deuteronation may slow down electron transfer in the electron transport chain (ETC) by interfering with proton coupled electron transport reactions (PCET), and increase free radical production through the leakage of temporarily accumulated electrons at the downstream complexes. CONCLUSION: Deuteronation, as exemplified by ATP synthase and the ETC, may interfere with the conformations and functions of many macromolecules and contribute to some pathologies like heavy water toxicity and aging.

Correlation between vascular endothelial growth factor and leptin in children with cyanotic congenital heart disease.

The objective in this study was to determine whether there was any relation between leptin and vascular endothelial growth factor (VEGF) in children with cyanotic and acyanotic heart anomalies. The study group consisted of 18 children with cyanotic congenital heart disease (CHD) and 20 age-adjusted children with acyanotic CHD as controls. Serum VEGF and leptin levels were determined by enzyme-linked immunosorbent assay (ELISA). The mean VEGF level was 149.25+/-42.93 pg/ml (range 80.66-217.00) in the cyanotic group and 88.18+/-20.94 pg/ml (range 48.44-112.71) in the acyanotic group (p<0.001). The mean leptin level was 7.55+/-1.46 ng/ml (range 4.08-10.25) in the cyanotic group and 6.89+/-1.43 ng/ml (range 2.67-8.57) in the acyanotic group (p=0.168). There was a significant positive correlation (r=0.723, p<0.001) between VEGF and leptin levels in the cyanotic group while there was no correlation (r=0.235, p=0.348) in the acyanotic group. Arterial oxygen saturation (SaO2) was negatively correlated (r=-0.625, p<0.001) with VEGF, but not correlated with leptin (r=-0.207, p=0.211) in the cyanotic group. There was no correlation between VEGF, leptin and SaO2 in the acyanotic group. We conclude that it is likely that both VEGF and leptin have a role in the pathogenesis of angiogenesis in cyanotic CHD.

Soluble CD40 ligand levels in otherwise healthy subjects with impaired fasting glucose.

Unlike diabetes mellitus and impaired glucose tolerance, it is not clear whether the subjects with impaired fasting glucose (IFG) are at increased risk of atherosclerosis and cardiovascular diseases. The CD40-CD40 ligand interaction is involved in the mechanism of atherosclerosis. We investigated whether soluble CD40L (sCD40L) as well as high sensitive C-reactive protein (hsCRP) levels are increased in subjects with IFG having no confounding factors for inflammation or atherosclerosis. Twenty four IFG subjects with no additional disorders and 40 appropriate healthy controls were studied. sCD40L and hsCRP levels in the IFG and control groups were similar. Blood pressures, total and LDL-cholesterol, and triglyceride levels were also similar, whereas HDL-cholesterol was lower and HOMA-IR indexes were higher in the IFG group. Though the sample size was small, the present data show that sCD40L seems not to alter in subjects with IFG suggesting that it might not be an independent risk factor for atherosclerosis.

Functional analysis of MRG-1: the ortholog of human MRG15 in Caenorhabditis elegans.

Mortality Factor on Chromosome 4 (MORF4) induces senescence in several immortal human cell lines. MORF-related gene on chromosome 15 (MRG15), another expressed family member, is highly conserved and expressed in yeast to humans. To determine the biological functions of human MRG15 (hMRG15) we used RNA-mediated interference (RNAi) to silence mrg-1, the Caenorhabditis elegans ortholog, and its closest homolog Y37D8A.11. Expression of mrg-1 RNAi resulted in sterility, body wall defects, vulval protrusion, and posterior developmental defects in worms. We expressed mrg-1 under its own and the cytomegalovirus promoter in human cells. Both constructs were expressed, indicating that C. elegans promoter elements are functional in mammalian cells. Overexpression from the cytomegalovirus promoter eventually resulted in cell death, possibly due to competition with hMRG15 in endogenous nucleoprotein complexes. Recent data indicate a role for yeast and human MRG15 in transcriptional regulation via chromatin remodeling. Here we demonstrate the importance of mrg-1 in development and reproduction in C. elegans and discuss its potential to impact the aging process.