γH2AX responses in human buccal cells exposed to ionizing radiation.

DNA double strand breaks are induced by ionizing radiation (IR), leading to the phosphorylation of the core histone protein H2AX (termed γH2AX). The understanding of the γH2AX responses in irradiated human buccal cells is still very limited. We used visual scoring and laser scanning cytometry (LSC) methods to investigate γH2AX signaling following exposure of human buccal cells (from six individuals) to ionizing radiation at 0-4 Gy. The frequency of nuclei containing 15-30 γH2AX foci was significantly elevated 30 min post-IR exposure (by visual scoring). Concomitantly, there was a significant decrease in the frequency of cells without foci following exposure to IR. IR-induced γH2AX signal as determined by laser scanning cytometry (which included γH2AX integral and MaxPixel value) increased significantly in all individual's 2N nuclei 30 min post-IR and was similar for all three nuclear shapes identified. Individuals with the lowest baseline γH2AX integral (i.e., in nonirradiated cells) showed the greatest fold stimulation of γH2AX and significant dose-responses to IR doses of 1, 2, and 4 Gy. In 5 out of 6 individuals, the frequency of visually scored γH2AX in nuclei showed a strong correlation (up to r = 0.999) with LSC scored γH2AX integrals. The γH2AX response and subsequent decline varied between individuals but remained elevated above baseline levels 24 h post IR exposure. γH2AX response in irradiated human buccal cells has potential to be used as an index of baseline DNA damage in population studies. The variable response to IR exposure between individuals should be taken into consideration when using the γH2AX assay for radiation biodosimetry.

Biomarkers of Nutrition for Development-Folate Review.

The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, iron, zinc, folate, vitamin A, and vitamin B-12. This review represents the second in the series of reviews and covers all relevant aspects of folate biology and biomarkers. The article is organized to provide the reader with a full appreciation of folate's history as a public health issue, its biology, and an overview of available biomarkers (serum folate, RBC folate, and plasma homocysteine concentrations) and their interpretation across a range of clinical and population-based uses. The article also includes a list of priority research needs for advancing the area of folate biomarkers related to nutritional health status and development.

Commentary: critical questions, misconceptions and a road map for improving the use of the lymphocyte cytokinesis-block micronucleus assay for in vivo biomonitoring of human exposure to genotoxic chemicals-a HUMN project perspective.

The lymphocyte cytokinesis-block micronucleus (CBMN) assay has been applied in hundreds of in vivo biomonitoring studies of humans exposed to genotoxic chemicals because it allows the measurement of both structural and numerical chromosome aberrations. The CBMN cytome assay version which, apart from measuring micronuclei (MN) already present in cells in vivo or expressed ex vivo, also includes measurement of nucleoplasmic bridges (NPB), nuclear buds (NBUD), necrosis and apoptosis, is also increasingly being used in such studies. Because of the numerous published studies there is now a need to re-evaluate the use of MN and other biomarkers within the lymphocyte CBMN cytome assay as quantitative indicators of exposure to chemical genotoxins and the genetic hazard this may cause. This review has identified some important misconceptions as well as knowledge gaps that need to be addressed to make further progress in the proper application of this promising technique and enable its full potential to be realised. The HUMN project consortium recommends a three pronged approach to further improve the knowledge base and application of the lymphocyte CBMN cytome assay to measure DNA damage in humans exposed to chemical genotoxins: (i) a series of systematic reviews, one for each class of chemical genotoxins, of studies which have investigated the association of in vivo exposure in humans with MN, NPB and NBUD induction in lymphocytes; (ii) a comprehensive analysis of the literature to obtain new insights on the potential mechanisms by which different classes of chemicals may induce MN, NPB and NBUD in vitro and in vivo and (iii) investigation of the potential advantages of using the lymphocyte CBMN cytome assay in conjunction with other promising complementary DNA damage diagnostics to obtain an even more complete assessment of the DNA damage profile induced by in vivo exposure to chemical genotoxins in humans.

Nutriomes and personalised nutrition for DNA damage prevention, telomere integrity maintenance and cancer growth control.

DNA damage at the base sequence and chromosome level is a fundamental cause of developmental and degenerative diseases. Multiple micronutrients and their interactions with the inherited and/or acquired genome determine DNA damage and genomic instability rates. The challenge is to identify for each individual the combination of micronutrients and their doses (i.e. the nutriome) that optimises genome stability, including telomere integrity and functionality and DNA repair. Using nutrient array systems with high-content analysis diagnostics of DNA damage, cell death and cell growth, it is possible to define, on an individual basis, the optimal nutriome for DNA damage prevention and cancer growth control. This knowledge can also be used to improve culture systems for cells used in therapeutics such as stem cells to ensure that they are not genetically aberrant when returned to the body. Furthermore, this information could be used to design dietary patterns that deliver the micronutrient combinations and concentrations required for preventing DNA damage by micronutrient deficiency or excess. Using this approach, new knowledge could be obtained to identify the dietary restrictions and/or supplementations required to control specific cancers, which is particularly important given that reliable validated advice is not yet available for those diagnosed with cancer.

Necrosis is increased in lymphoblastoid cell lines from children with autism compared with their non-autistic siblings under conditions of oxidative and nitrosative stress.

Autism spectrum disorders are a heterogeneous group of neurodevelopmental conditions characterised by impairments in reciprocal social interaction, communication and stereotyped behaviours. As increased DNA damage events have been observed in a range of other neurological disorders, it was hypothesised that they would be elevated in lymphoblastoid cell lines (LCLs) obtained from children with autism compared with their non-autistic siblings. Six case-sibling pairs of LCLs from children with autistic disorder and their non-autistic siblings were obtained from the Autism Genetic Resource Exchange (AGRE) and cultured in standard RPMI-1640 tissue culture medium. Cells were exposed to medium containing either 0, 25, 50, 100 and 200 µM hydrogen peroxide (an oxidative stressor) or 0, 5, 10, 20 and 40 µM s-nitroprusside (a nitric oxide producer) for 1h. Following exposure, the cells were microscopically scored for DNA damage, cytostasis and cytotoxicity biomarkers as measured using the cytokinesis-block micronucleus cytome assay. Necrosis was significantly increased in cases relative to controls when exposed to oxidative and nitrosative stress (P = 0.001 and 0.01, respectively). Nuclear division index was significantly lower in LCLs from children with autistic disorder than their non-autistic siblings when exposed to hydrogen peroxide (P = 0.016), but there was no difference in apoptosis, micronucleus frequency, nucleoplasmic bridges or nuclear buds. Exposure to s-nitroprusside significantly increased the number of micronuclei in non-autistic siblings compared with cases (P = 0.003); however, other DNA damage biomarkers, apoptosis and nuclear division did not differ significantly between groups. The findings of this study show (i) that LCLs from children with autism are more sensitive to necrosis under conditions of oxidative and nitrosative stress than their non-autistic siblings and (ii) refutes the hypothesis that children with autistic disorder are abnormally susceptible to DNA damage.

Protective Effects of Micronutrient Supplements, Phytochemicals and Phytochemical-Rich Beverages and Foods Against DNA Damage in Humans: A Systematic Review of Randomized Controlled Trials and Prospective Studies.

Accumulation of deoxyribonucleic acid (DNA) damage diminishes cellular health, increases risk of developmental and degenerative diseases, and accelerates aging. Optimizing nutrient intake can minimize accrual of DNA damage. The objectives of this review are to: 1) assemble and systematically analyze high-level evidence for the effect of supplementation with micronutrients and phytochemicals on baseline levels of DNA damage in humans, and 2) use this knowledge to identify which of these essential micronutrients or nonessential phytochemicals promote DNA integrity in vivo in humans. We conducted systematic literature searches of the PubMed database to identify interventional, prospective, cross-sectional, or in vitro studies that explored the association between nutrients and established biomarkers of DNA damage associated with developmental and degenerative disease risk. Biomarkers included lymphocyte chromosome aberrations, lymphocyte and buccal cell micronuclei, DNA methylation, lymphocyte/leukocyte DNA strand breaks, DNA oxidation, telomere length, telomerase activity, and mitochondrial DNA mutations. Only randomized, controlled interventions and uncontrolled longitudinal intervention studies conducted in humans were selected for evaluation and data extraction. These studies were ranked for the quality of their study design. In all, 96 of the 124 articles identified reported studies that achieved a quality assessment score ≥ 5 (from a maximum score of 7) and were included in the final review. Based on these studies, nutrients associated with protective effects included vitamin A and its precursor ß-carotene, vitamins C, E, B1, B12, folate, minerals selenium and zinc, and phytochemicals such as curcumin (with piperine), lycopene, and proanthocyanidins. These findings highlight the importance of nutrients involved in (i) DNA metabolism and repair (folate, vitamin B12, and zinc) and (ii) prevention of oxidative stress and inflammation (vitamins A, C, E, lycopene, curcumin, proanthocyanidins, selenium, and zinc). Supplementation with certain micronutrients and their combinations may reduce DNA damage and promote cellular health by improving the maintenance of genome integrity.

Application and adaptation of the in vitro micronucleus assay for the assessment of nutritional requirements of cells for DNA damage prevention.

DNA damage is a fundamental cause of developmental and degenerative diseases. The in vitro cytokinesis-block micronucleus cytome (CBMN-Cyt) assay is an established comprehensive method for assessing cytostasis and chromosome stability in cells. Originally developed to study the acute effects of single environmental genotoxicants, creative applications and adaptations to the basic protocol have allowed its use in evaluating the impacts of dietary micronutrients and micronutrient combinations (nutriomes) on DNA damage. In this review, we examine some of these studies and the important findings they have generated with respect to nutrient/nutrient, nutrient/genotype and nutrient/genotoxicant interactions, as well as assessment of the carcinogenic (or protective) potential of whole dietary patterns. In addition, we outline current knowledge gaps and technical limitations and propose future adaptations to enhance the applicability of the CBMN-Cyt method for in vivo predictions.

Effects of Micronutrient Supplementation on Glucose and Hepatic Lipid Metabolism in a Rat Model of Diet Induced Obesity.

Obesity increases the risk of metabolic disorders, partly through increased oxidative stress. Here, we examined the effects of a dietary micronutrient supplement (consisting of folate, vitamin B6, choline, betaine, and zinc) with antioxidant and methyl donor activities. Male Sprague Dawley rats (3 weeks old, 17/group) were weaned onto control (C) or high-fat diet (HFD) or same diets with added micronutrient supplement (CS; HS). At 14.5 weeks of age, body composition was measured by magnetic resonance imaging. At 21 weeks of age, respiratory quotient and energy expenditure was measured using Comprehensive Lab Animal Monitoring System. At 22 weeks of age, an oral glucose tolerance test (OGTT) was performed, and using fasting glucose and insulin values, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated as a surrogate measure of insulin resistance. At 30.5 weeks of age, blood and liver tissues were harvested. Liver antioxidant capacity, lipids and expression of genes involved in lipid metabolism (Cd36, Fabp1, Acaca, Fasn, Cpt1a, Srebf1) were measured. HFD increased adiposity (p < 0.001) and body weight (p < 0.001), both of which did not occur in the HS group. The animals fed HFD developed impaired fasting glucose, impaired glucose tolerance, and fasting hyperinsulinemia compared to control fed animals. Interestingly, HS animals demonstrated an improvement in fasting glucose and fasting insulin. Based on insulin release during OGTT and HOMA-IR, the supplement appeared to reduce the insulin resistance developed by HFD feeding. Supplementation increased hepatic glutathione content (p < 0.05) and reduced hepatic triglyceride accumulation (p < 0.001) regardless of diet; this was accompanied by altered gene expression (particularly of CPT-1). Our findings show that dietary micronutrient supplementation can reduce weight gain and adiposity, improve glucose metabolism, and improve hepatic antioxidant capacity and lipid metabolism in response to HFD intake.

Evaluation of GammaH2AX in Buccal Cells as a Molecular Biomarker of DNA Damage in Alzheimer's Disease in the AIBL Study of Ageing.

In response to double-stranded breaks (DSBs) in chromosomal DNA, H2AX (a member of histone H2A family) becomes phosphorylated to form γH2AX. Although increased levels of γH2AX have been reported in the neuronal nuclei of Alzheimer's disease (AD) patients, the understanding of γH2AX responses in buccal nuclei of individuals with mild cognitive impairment (MCI) and AD remain unexplored. In the current study, endogenous γH2AX was measured in buccal cell nuclei from MCI (n = 18) or AD (n = 16) patients and in healthy controls (n = 17) using laser scanning cytometry (LSC). The γH2AX level was significantly elevated in nuclei of the AD group compared to the MCI and control group, and there was a concomitant increase in P-trend for γH2AX from the control group through MCI to the AD group. Receiver-operating characteristic curves were carried out for different γH2AX parameters; γH2AX in nuclei resulted in the greatest area under the curve value of 0.7794 (p = 0.0062) with 75% sensitivity and 70% specificity for the identification of AD patients from control. In addition, nuclear circularity (a measure of irregular nuclear shape) was significantly higher in the buccal cell nuclei from the AD group compared with the MCI and control groups. Additionally, there was a positive correlation between the nuclear circularity and γH2AX signals. The results indicated that increased DNA damage is associated with AD.

The effect of selenium, as selenomethionine, on genome stability and cytotoxicity in human lymphocytes measured using the cytokinesis-block micronucleus cytome assay.

A supranutritional intake of selenium (Se) may be required for cancer prevention, but an excessively high dose could be toxic. Therefore, the effect on genome stability of seleno-L-methionine (Se-met), the most important dietary form of Se, was measured to determine its bioefficacy and safety limit. Peripheral blood lymphocytes were isolated from six volunteers and cultured with medium supplemented with Se-met in a series of Se concentrations (3, 31, 125, 430, 1880 and 3850 microg Se/litre) while keeping the total methionine (i.e. Se-met + L-methionine) concentration constant at 50 microM. Baseline genome stability of lymphocytes and the extent of DNA damage induced by 1.5-Gy gamma-ray were investigated using the cytokinesis-block micronucleus cytome assay after 9 days of culture in 96-microwell plates. High Se concentrations (>or=1880 microg Se/litre) caused strong inhibition of cell division and increased cell death (P < 0.0001). Baseline frequency of nucleoplasmic bridges and nuclear buds, however, declined significantly (P trend < 0.05) as Se concentration increased from 3 to 430 microg Se/litre. Se concentration (

The molecular origins and pathophysiological consequences of micronuclei: New insights into an age-old problem.

Micronuclei (MN), the small nucleus-like bodies separated from the primary nucleus, can exist in cells with numerical and/or structural chromosomal aberrations in apparently normal tissues and more so in tumors in humans. While MN have been observed for over 100 years, they were merely and constantly considered as passive indicators of chromosome instability (CIN) for a long time. Relatively little is known about the molecular origins and biological consequences of MN. Rapid technological advances are helping to close these gaps. Very recent studies provide exciting evidence that MN act as key platform for chromothripsis and a trigger of innate immune response, suggesting that MN could affect cellular functions by both genetic and nongenetic means. These previously unappreciated findings have reawakened widespread interests in MN. In this review, the diverse mechanisms leading to MN generation and the complex fate profiles of MN are discussed, together with the evidence for their contribution to CIN, inflammation, senescence and cell death. Moreover, we put this knowledge together into a speculative perspective on how MN may be responsible for cancer development and how their presence may influence the choice of treatment. We suggest that the heterogeneous responses to MN may function physiological to ensure the arrestment, elimination and immune clearance of damaged cells, but pathologically, may enable the survival and oncogenic transformation of cells bearing CIN. These insights not only underscore the complexity of MN biology, but also raise a host of new questions and provide fertile ground for future research.

Current State of Saliva Biomarkers for Aging and Alzheimer's Disease.

INTRODUCTION: Aging is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases such as Alzheimer's Disease (AD). AD is a progressive degenerative disorder of the brain and is the most common form of dementia. METHODS: To-date no simple, inexpensive and minimally invasive procedure is available to confirm with certainty the early diagnosis of AD prior to the manifestations of symptoms characteristic of the disease. Therefore, if population screening of individuals is to be performed, easily accessible tissues would need to be used for a diagnostic test that would identify those who exhibit altered or aberrant aging profiles that may be indicative of AD risk, so that they can be prioritized for primary prevention. This need for minimally invasive tests could be achieved by targeting saliva, since it is now well recognized that many aging diseases including AD are associated with peripheral biomarkers that are not only restricted to pathology and biomarkers within the brain. RESULTS: Therefore, the aim of this review is to summarize some of the main findings of salivary biomarkers of aging and AD; including various proteins, metabolites, and alterations to DNA and miRNA. The future of healthy aging resides in innovative platforms, biosensors and point-of-care devices that can extract real time information on the health status of an individual. Those platforms may be achieved through the development and validation of novel biomarkers of health using saliva which, although being the least explored for biomedical purposes, has the distinct advantage that it can be self-collected in a non-invasive manner.

One-carbon metabolism enzyme polymorphisms and uteroplacental insufficiency.

OBJECTIVES: This study was undertaken to test novel genetic polymorphisms involved in 1-carbon metabolism for a potential association with increased risk of developing pregnancy complications associated with uteroplacental insufficiency. STUDY DESIGN: This was a prospective cohort study consisting of 50 women at low risk and 93 women at high risk for having a pregnancy complication develop. Maternal and fetal DNA samples were genotyped for methionine synthase (MTR) A2756G, methionine synthase reductase (MTRR) A66G and methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A. A chi squared or chi(2) analysis was used to compare genotypes and pregnancy outcome, 1-way analysis of variance and linear regression were used to compare genotype with continuous variables. RESULTS: The fetal MTR 2756 G allele was associated with uteroplacental insufficiency (P = .022, likelihood ratio = 10.4) and maternal homocysteine (P = .017). The maternal MTR A2756G polymorphism was associated with uteroplacental insufficiency (P = .049, likelihood ratio = 6.0), but only in mothers not supplementing with high-dose B-vitamins. The maternal MTHFD1 AA genotype was associated with intrauterine growth restriction (P = .047, likelihood ratio = 5.8). CONCLUSION: This study suggests the maternal and fetal MTR 2756 G allele is an important risk factor in the development of uteroplacental insufficiency. In addition, the maternal MTHFD1 1958 AA genotype may be associated with intrauterine growth restriction.

Genome instability is increased in lymphocytes of women with polycystic ovary syndrome and is correlated with insulin resistance.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and reproductive and metabolic abnormalities. The potential genetic contributors to PCOS are unclear. We tested the hypothesis that genomic instability (chromosome malsegregation and DNA damage) is increased in PCOS. METHODS: Overweight age, weight and BMI-matched women with (n=14) and without (n=16) PCOS (age 34.2+/-6.0 years, weight 90.7+/-14.5 kg, BMI 34.0+/-5.6 kg/m(2), mean+/-S.D.) were assessed for chromosome malsegregation (assessed by X chromosome chromogenic in situ hybridisation) and micronucleus frequency (assessed by the cytokinesis block micronucleus index) in lymphocytes. RESULTS: Women with PCOS had significantly elevated genomic instability as demonstrated by a significantly higher number of binucleated lymphocytes containing micronuclei, total number of micronuclei, a higher proportion of aneuploid X chromosome signals (2:1 X and 3:1 X) and a lower proportion of normal X chromosome segregation signals (2:2 X) in binucleated lymphocytes than women without PCOS. Surrogate measures of insulin resistance positively correlated with the proportion of aneuploid cells (2:1; 3:1 X chromosome signals) and inversely with the proportion of normal cells (2:2 X chromosome signals). CONCLUSION: Women with PCOS display increased genomic instability (higher micronuclei and chromosome malsegregation) compared to women without PCOS and this increase may be related to the insulin resistance phenotype.

Nutritionally recommended food for semi- to strict vegetarian diets based on large-scale nutrient composition data.

Diet design for vegetarian health is challenging due to the limited food repertoire of vegetarians. This challenge can be partially overcome by quantitative, data-driven approaches that utilise massive nutritional information collected for many different foods. Based on large-scale data of foods' nutrient compositions, the recent concept of nutritional fitness helps quantify a nutrient balance within each food with regard to satisfying daily nutritional requirements. Nutritional fitness offers prioritisation of recommended foods using the foods' occurrence in nutritionally adequate food combinations. Here, we systematically identify nutritionally recommendable foods for semi- to strict vegetarian diets through the computation of nutritional fitness. Along with commonly recommendable foods across different diets, our analysis reveals favourable foods specific to each diet, such as immature lima beans for a vegan diet as an amino acid and choline source, and mushrooms for ovo-lacto vegetarian and vegan diets as a vitamin D source. Furthermore, we find that selenium and other essential micronutrients can be subject to deficiency in plant-based diets, and suggest nutritionally-desirable dietary patterns. We extend our analysis to two hypothetical scenarios of highly personalised, plant-based methionine-restricted diets. Our nutrient-profiling approach may provide a useful guide for designing different types of personalised vegetarian diets.

The potential for complete automated scoring of the cytokinesis block micronucleus cytome assay using imaging flow cytometry.

The lymphocyte Cytokinesis-Block Micronucleus (CBMN) assay was originally developed for the measurement of micronuclei (MN) exclusively in binucleated (BN) cells, which represent the population of cells that can express MN because they completed nuclear division. Recently the assay has evolved into a comprehensive cytome method to include biomarkers that measure chromosomal instability and cytotoxicity by quantification of nuclear buds (NBUDs), nucleoplasmic bridges (NPBs) and apoptotic/necrotic cells. Furthermore, enumeration of mono- and polynucleated cells allows for computation of the nuclear division index (NDI) to assess mitotic activity. Typically performed by manual microscopy, the CBMN cytome assay is laborious and subject to scorer bias and fatigue, leading to inter- and intra-scorer variability. Automated microscopy and conventional flow cytometry methods have been developed to automate scoring of the traditional and cytome versions of the assay. However, these methods have several limitations including the requirement to create high-quality microscope slides, lack of staining consistency and sub-optimal nuclear/cytoplasmic visualization. In the case of flow cytometry, stripping of the cytoplasmic membrane makes it impossible to measure MN in BN cells, calculate the NDI or to quantify apoptotic or necrotic cells. Moreover, the absence of cellular visualization using conventional flow cytometry, makes it impossible to quantify NBUDs and NPBs. In this review, we propose that imaging flow cytometry (IFC), which combines high resolution microscopy with flow cytometry, may overcome these limitations. We demonstrate that by using IFC, images from cells in suspension can be captured, removing the need for microscope slides and allowing visualization of intact cytoplasmic membranes and DNA content. Thus, mono-, bi- and polynucleated cells with and without MN can be rapidly and automatically identified and quantified. Finally, we present high-resolution cell images containing NBUDs and NPBs, illustrating that IFC possesses the potential for completely automated scoring of all components of the CBMN cytome assay.

γH2AX is increased in peripheral blood lymphocytes of Alzheimer's disease patients in the South Australian Neurodegeneration, Nutrition and DNA Damage (SAND) study of aging.

An early cellular response to DNA double-strand breaks is the phosphorylation of histone H2AX to form γH2AX. Although increased levels of γH2AX have been reported in neuronal nuclei of Alzheimer's disease (AD) patients, γH2AX responses in the lymphocytes of individuals with mild cognitive impairment (MCI) and AD remain unexplored. In this study, the endogenous γH2AX level was measured, using laser scanning cytometry (LSC) and visual scoring, in lymphocyte nuclei from MCI (n = 18), or AD (n = 20) patients and healthy controls (n = 40). Levels were significantly elevated in nuclei of the AD group compared to the MCI and control groups, and there was a concomitant increase, with a significant trend, from the control group through MCI to the AD group. A significant negative correlation was seen between γH2AX and the mini mental state examination (MMSE) score, when the analysis included all subjects. Receiver Operation Characteristic curves were carried out for different γH2AX parameters; visually scored percent cells containing overlapping γH2AX foci displayed the best area under the curve value of 0.9081 with 85% sensitivity and 92% specificity for the identification of AD patients versus control. Plasma homocysteine, creatinine, and chitinase-3-like protein 1 (CHI3L1) were positively correlated with lymphocyte γH2AX signals, while glomerular filtration rate (GFR) was negatively correlated. Finally, there was a diminished γH2AX response to X-rays in lymphocytes of the MCI and AD groups compared to the control group. Our results indicate that lymphocyte γH2AX levels are a potential marker for identifying individuals at increased risk of developing AD. Prospective studies with normal healthy individuals are needed to test whether there is indeed a link between γH2AX levels and AD risk.

Shorter telomere length in people with schizophrenia: A preliminary study from Australia.

Schizophrenia is a complex mental illness affecting the normal functioning of the brain, interfering with the ability to think, feel and act. It can be conceptualised as a syndrome of accelerated ageing, with early onset of cardiovascular disease and high rates of premature mortality. Telomere attrition increases with oxidative stress and is considered a biomarker of ageing. Previous studies have assessed abnormalities in telomere length in schizophrenia, but the results are inconsistent. The present study used a case-control design to assess whether people with schizophrenia have shortened telomeres, indicative of accelerated ageing. Subjects were all male, aged 25-35years, living in the same urban region of Adelaide, South Australia. Telomere length was measured using a quantitative real-time polymerase chain reaction (PCR) method. We found significantly shorter telomeres in people with schizophrenia relative to healthy controls. This is the first study to show telomere attrition among people with schizophrenia in Australia. Shorter telomere length may indicate the common pathways that schizophrenia shares with other neuropsychiatric and neurodevelopmental disorders associated with increased cellular senescence. Further well-controlled larger studies in people with schizophrenia are required to fully understand (i) the role of variables that have the potential to modulate telomere length such as use of antipsychotic drugs, medical conditions, parental age, smoking, alcohol abuse and use of illicit drugs; (ii) effective treatments to slow telomere erosion and (iii) mechanisms responsible for accelerating and reducing telomere damage.