Telomere therapy for chronic kidney disease
- Authors: Akinnibosun, Olutope , Maier, Michelle , Eales, James , Tomaszewski, Maciej , Charchar, Fadi
- Date: 2022
- Type: Text , Journal article
- Relation: Epigenomics Vol. 14, no. 17 (2022), p. 1039-1054
- Full Text: false
- Reviewed:
- Description: Chronic kidney disease (CKD) is estimated to affect almost 10% of individuals worldwide and is one of the leading causes of morbidity and mortality. Renal fibrosis, a central pathway in CKD progression (irrespective of etiology), is associated with shortened or dysfunctional telomeres in animal studies. Telomeres are specialized nucleoprotein structures located at the chromosome end that maintain genomic integrity. The mechanisms of associations between telomere length and CKD have not yet been fully elucidated, however, CKD patients with shorter telomere length may have decreased renal function and a higher mortality rate. A plethora of ongoing research has focused on possible therapeutic applications of telomeres with the overall goal to preserve telomere length as a therapy to treat CKD. Chronic kidney disease or CKD is one of the leading causes of illness and death worldwide. Scarring of the kidney tissue that occurs in CKD has been associated with shorter telomeres in studies using rats. Telomeres, said to act as the cellular ‘shoelace caps’, maintain the structure of chromosomes, allowing for genetic material inside cells to divide correctly. The length of telomeres (TL) is influenced by diverse factors such as genetics and lifestyle. The underlying processes for the associations between TL and CKD are still not understood, however, patients with CKD and shorter TL have reduced kidney function and an increased death rate. Therefore, research is focused on possible ways to preserve TL and treat CKD. Preserving telomere length may reduce rates of chronic kidney disease, thereby decreasing morbidity & mortality worldwide.
A MicroRNA Guide for Clinicians and Basic Scientists : Background and Experimental Techniques
- Authors: Bernardo, Bianca , Charchar, Fadi , Lin, Ruby , McMullen, Julie
- Date: 2012
- Type: Text , Journal article
- Relation: Heart Lung and Circulation Vol. 21, no. 3 (2012), p. 131-142
- Full Text: false
- Reviewed:
- Description: MicroRNAs (miRNAs) are short non-coding RNA molecules that are approximately 22 nucleotides in length. In the last 10. years, miRNA research and discovery has advanced at a rapid rate. This review provides a brief overview of the discovery and biology of miRNAs, and summarises some of the experimental techniques used for isolation, detection, target prediction, and regulation of miRNAs. We also outline experimental workflows for investigators new to the field, and discuss the diagnostic and therapeutic application of miRNAs. © 2011 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
Coronary artery disease predisposing haplogroup I of the Y chromosome, aggression and sex steroids - Genetic association analysis
- Authors: Bloomer, Lisa , Nelson, Christopher , Denniff, Matthew , Christofidou, Paraskevi , Debiec, Radoslaw , Thompson, John , Zukowska-Szczechowska, Ewa , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2014
- Type: Text , Journal article
- Relation: Atherosclerosis Vol. 233, no. 1 (2014), p. 160-164
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text: false
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- Description: Objective: Amongst middle-aged men, haplogroup I is associated with approximate to 50% higher risk of coronary artery disease than other paternal lineages of Y chromosome. We hypothesised that carriers of haplogroup I had higher levels of aggression and estrogens and/or lower levels of androgens early in life and thus might be more prone to cardiovascular disease than men with other lineages of Y chromosome. Methods: We reconstructed phylogenetic tree of the Y chromosome in > 1000 young apparently healthy white men from the general population. Each Y chromosome was classified into one of 13 most common European lineages. Androgens (DHEA-S, androstenedione, total testosterone) and their metabolites (total estradiol, estrone) were measured by radioimmunoassays. Information on five dimensions of aggression (total, physical, verbal, anger and hostility) was collected using Buss and Perry questionnaire. Results: Approximately 17% men inherited haplogroup I from their fathers. Carriers of haplogroup I showed lower scores of verbal aggression than men with other haplogroups (beta = -0.72, SE = 0.29, P = 0.012) and when further compared to carriers of most common R1a lineage and other haplogroups (beta = -1.03, SE = 0.34, P = 0.003). However, these associations did not survive a correction for multiple testing. Sex steroids did not show even nominal level of association with haplogroup I. Conclusion: Our data show no overall association between haplogroup I and sex-related phenotypes in young white men. These results also suggest that the previously identified association between haplogroup I and coronary artery disease is not likely mediated by unfavourable profile of sex steroids or heightened aggression early in life. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
MicroRNA-34a and tert act as epi-drivers of cardiac telomere length and polygenic cardiac hypertrophy
- Authors: Booth, Scott , Marques, Francine , Prestes, Priscilla , Curl, Claire , Delbridge, Lea , Lewandowski, Paul , Harrap, Stephen , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Heart, Lung and Circulation Vol. 24, no. S3 (2015), p. S180-S181
- Full Text: false
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- Description: Cardiac hypertrophy is one of the main risk factors forheart failure. Here we aimed to investigate whether cardiactelomere length contributes to polygenic cardiac hypertro-phy independent of blood pressure. We also investigatedwhether changes in telomere length were due to the telomereregulators microRNA-34a,Ppp1r10(also known asPnuts)and telomerase. We used the hypertrophic heart rat (HHR),a normotensive model of polygenetic cardiac hypertrophy,and compared it to age-matched controls. Telomere length, microRNA levels, gene expression and telomerase activitywere measured in isolated cardiomyocytes and left ventricletissue using real-time PCR. Telomere length was significantlylonger in 2-day and 38-week-old HHR, but shorter at 4-and 13-week HHR. In the HHR, telomere length becameshorter early in development, while in the control straintelomere shortening was only observed in late adulthood.Telomere length was the main determinant of cardiac mass.
Cardiac telomere length in heart development, function, and disease
- Authors: Booth, Scott , Charchar, Fadi
- Date: 2017
- Type: Text , Journal article , Review
- Relation: Physiological Genomics Vol. 49, no. 7 (2017), p. 368-384
- Relation: http://purl.org/au-research/grants/nhmrc/1034371
- Full Text: false
- Reviewed:
- Description: Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury. © 2017 the American Physiological Society.
Orthologues of GSTM expressed in human kidney
- Authors: Brosnan, Julia , Tomaszewski, Maciej , McBride, Martin , Charchar, Fadi , Lacka, Beata , Zukowska-Szczechowska, Ewa , Grzeszczak, Wladyslaw , Lee, Wai , Dominiczak, Anna
- Date: 2004
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 22, no. Suppl. 1 (2004), p. S183
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Report of the 3rd annual International Society of Hypertension New Investigator Symposium.
- Authors: Burger, Dylan , Veerabhadrappa, Praveen , Charchar, Fadi , Schutte, Aletta , Tomaszewski, Maciej
- Date: 2014
- Type: Text , Journal article
- Relation: Journal of hypertension Vol. 32, no. 4 (2014), p. 448-449
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Report of the first International Society of Hypertension (ISH) Trainee/new investigator symposium : A global hypertension initiative
- Authors: Burger, Dylan , Veerabhadrappa, Praveen , Charchar, Fadi , Tomaszewski, Maciej , Harrap, Stephen , Carlberg, Bo , Touyz, Rhian
- Date: 2012
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 30, no. 3 (2012), p. 631-632
- Full Text: false
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The epithelial sodium channel y-subunit gene and blood pressure : Family based association, renal gene expression, and physiological analyses
- Authors: Büsst, Cara , Bloomer, Lisa , Scurrah, Katrina , Ellis, Justine , Barnes, Timothy , Charchar, Fadi , Braund, Peter , Hopkins, Paul , Samani, Nilesh , Hunt, Steven , Tomaszewski, Maciej , Harrap, Stephen
- Date: 2011
- Type: Text , Journal article
- Relation: Hypertension Vol. 58, no. 6 (2011), p. 1073-1078
- Full Text: false
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- Description: Variants in the gene encoding the y-subunit of the epithelial sodium channel (SCNN1G) are associated with both Mendelian and quantitative effects on blood pressure. Here, in 4 cohorts of 1611 white European families composed of a total of 8199 individuals, we undertook staged testing of candidate single-nucleotide polymorphisms for SCNN1G (supplemented with imputation based on data from the 1000 Genomes Project) followed by a meta-analysis in all of the families of the strongest candidate. We also examined relationships between the genotypes and relevant intermediate renal phenotypes, as well as expression of SCNN1G in human kidneys. We found that an intronic single-nucleotide polymorphism of SCNN1G (rs13331086) was significantly associated with age-, sex-, and body mass index-adjusted blood pressure in each of the 4 populations (P<0.05). In an inverse variance-weighted meta-analysis of this single-nucleotide polymorphism in all 4 of the populations, each additional minor allele copy was associated with a 1-mm Hg increase in systolic blood pressure and 0.52-mm Hg increase in diastolic blood pressure (SE=0.33, P=0.002 for systolic blood pressure; SE=0.21, P=0.011 for diastolic blood pressure). The same allele was also associated with higher 12-hour overnight urinary potassium excretion (P=0.04), consistent with increased epithelial sodium channel activity. Renal samples from hypertensive subjects showed a nonsignificant (P=0.07) 1.7-fold higher expression of SCNN1G compared with normotensive controls. These data provide genetic and phenotypic evidence in support of a role for a common genetic variant of SCNN1G in blood pressure determination. © 2011 American Heart Association, Inc.
2022 World Hypertension League, resolve to save lives and International Society of Hypertension dietary sodium (salt) global call to action
- Authors: Campbell, Norm , Whelton, Paul , Orias, Marcelo , Wainford, Richard , Cappuccio, Francesco , Ide, Nicole , Neal, Bruce , Cohn, Jennifer , Cobb, Laura , Webster, Jacqui , Trieu, Kathy , He, Feng , McLean, Rachael , Blanco-Metzler, Adriana , Woodward, Mark , Khan, Nadia , Kokubo, Yoshihiro , Nederveen, Leo , Arcand, JoAnne , MacGregor, Graham , Owolabi, Mayowa , Lisheng, Liu , Parati, Gianfranco , Lackland, Daniel , Charchar, Fadi , Williams, Bryan , Tomaszewski, Maciej , Romero, Cesar , Champagne, Beatriz , L’Abbe, Mary
- Date: 2023
- Type: Text , Journal article
- Relation: Journal of Human Hypertension Vol. 37, no. 6 (2023), p. 428-437
- Full Text: false
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Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma
- Authors: Chambers, John , Zhang, Weihua , Sehmi, Joban , Li, Xinzhong , Wass, Mark N , van der Harst, Pim , Holm, Hilma , Sanna, Serena , Kavousi, Maryam , Charchar, Fadi
- Date: 2011
- Type: Text , Journal article
- Relation: Nature genetics Vol. 43, no. 11 (2011), p. 1131-1138
- Full Text: false
- Reviewed:
- Description: Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10−8 to P = 10−190). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function. 137 authors
Whole genome survey of copy number variation in the spontaneously hypertensive rat
- Authors: Charchar, Fadi , Samani, Nilesh
- Date: 2008
- Type: Text , Journal article
- Relation: Hypertension Vol. 52, no. 4 (Oct 2008), p. E100-E100
- Full Text: false
- Reviewed:
- Description: C1
Whole genome survey of copy number variation between the spontaneously hypersensitive rat and the wistar-kyoto rat
- Authors: Charchar, Fadi , Dixon, Richard , Kaiser, Michael , Bingham, Andrew , Samani, Nilesh
- Date: 2009
- Type: Text , Journal article
- Relation: Hypertension Vol. 53, no. 6 (2009), p. 1103-1104
- Full Text: false
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The pressure of finding human hypertension genes : New tools, old dilemmas
- Authors: Charchar, Fadi , Zimmerli, Lukas , Tomaszewski, Maciej
- Date: 2008
- Type: Text , Journal article
- Relation: Journal of Human Hypertension Vol. 22, no. (2008), p. 821–828
- Full Text: false
- Reviewed:
- Description: Researchers in hypertension genetics feel like they are left behind again. It always seems that the 'other' complex diseases are ahead in the race. Evolving new technologies in the form of genome-wide arrays and 'omics' technologies mean that investigators can now potentially identify many novel disease factors in one large-scale experiment. Hypertension research now faces the challenge of where to go next after the first genome-wide association experiments failed to provide robust candidates. In this review, we contemplate the old dilemma of whether such genes may ever be found; however, we believe advancing technologies and plummeting costs of large-scale experiments will contribute to the identification of novel molecules that underlie essential hypertension.
Y chromosome haplogroup as a novel biological risk factor for coronary artery disease - The results of tracking paternal lineages in the west of Scotland primary prevention study (WOSCOPS)
- Authors: Charchar, Fadi , Tomaszewski, Maciej , Barnes, Timothy , Wang, Y. , Brouilette, S. W. , Codd, Veryan , Bani-Mustafa, Ahmed , Padmanabhan, Sandosh , Dominiczak, Anna , Ford, I. , Samani, Nilesh
- Date: 2009
- Type: Text , Conference paper
- Relation: , p. S448-S448
- Full Text: false
Whole genome survey of copy number variation in the spontaneously hypertensive rat relationship to quantitative trait loci, gene expression, and blood pressure
- Authors: Charchar, Fadi , Kaiser, Michael , Bingham, Andrew , Fotinatos, Nina , Ahmady, Fahima , Tomaszewski, Maciej , Samani, Nilesh
- Date: 2010
- Type: Text , Journal article
- Relation: Hypertension Vol. 55, no. 5 (2010), p. 1231-1238
- Full Text: false
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- Description: Copy number variation has emerged recently as an important genetic mechanism leading to phenotypic heterogeneity. The aim of our study was to determine whether copy number variants (CNVs) exist between the spontaneously hypertensive rat (SHR) and its control strain, the Wistar-Kyoto rat, whether these map to quantitative trait loci in the rat and whether CNVs associate with gene expression or blood pressure differences between the 2 strains. We performed a comparative genomic hybridization assay between SHR and Wistar-Kyoto strains using a whole-genome array. In total, 16 CNVs were identified and validated (6 because of a relative loss of copy number in the SHR and 10 because of a relative gain). CNVs were present on rat autosomes 1, 3, 4, 6, 7, 10, 14, and 17 and varied in size from 10.0 kb to 1.6 Mb. Most of these CNVs mapped to chromosomal regions within previously identified quantitative trait loci, including those for blood pressure in the SHR. Transcriptomic experiment! s confirmed differences in the renal expression of several genes (including Ms4a6a, Ndr3, Egln1, Cd36, Sema3a, Ugt2b, and Idi21) located in some of the CNVs between STIR and Wistar-Kyoto rats. In F-2 animals derived from an SHRXWistar-Kyoto cross, we also found a significant increase in blood pressure associated with an increase in copy number in the Egln1 gene. Our findings suggest that, CNVs may play a role in the susceptibility to hypertension and related trails in the SHR. (Hypertension. 2010;55:1231-1238.)
RNA sequencing data from the human kidney
- Authors: Charchar, Fadi
- Date: 2013
- Type: Text , Dataset
- Full Text: false
- Description: The aims of the project to determine the molecular cause of human hypertension. We will be studying abnormalities in the expression of RNA in human kidneys. RNA is the message by which DNA or our genes are expressed as protein that makes up most of the cell and its function. The data will consist of RNA sequences and saved as .txt .seq files using the Partek software. The collection contains a sample of 30 items. The data has been processed using sequencing software and collected by the http://www.agrf.org.au Australian Genome Research Facility http://www.agrf.org.au and is funded by a NHMRC project called the effect of non-coding RNA in human hypertension.
Inheritance of coronary artery disease in men : An analysis of the role of the y chromosome
- Authors: Charchar, Fadi , Bloomer, Lisa , Barnes, Timothy , Cowley, Mark , Nelson, Christopher , Wang, Yanzhong , Denniff, Matthew , Debiec, Radoslaw , Christofidou, Paraskevi , Nankervis, Scott , Dominiczak, Anna , Bani-Mustafa, Ahmed , Balmforth, Anthony , Hall, Alistair , Erdmann, Jeanette , Cambien, Francois , Deloukas, Panos , Hengstenberg, Christian , Packard, Chris , Schunkert, Heribert , Ouwehand, Willem , Ford, Ian , Goodall, Alison , Jobling, Mark , Samani, Nilesh , Tomaszewski, Maciej
- Date: 2012
- Type: Text , Journal article
- Relation: The Lancet Vol. 379, no. 9819 (2012), p. 915-922
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text: false
- Reviewed:
- Description: Background: A sexual dimorphism exists in the incidence and prevalence of coronary artery disease - men are more commonly affected than are age-matched women. We explored the role of the Y chromosome in coronary artery disease in the context of this sexual inequity. Methods: We genotyped 11 markers of the male-specific region of the Y chromosome in 3233 biologically unrelated British men from three cohorts: the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study. On the basis of this information, each Y chromosome was tracked back into one of 13 ancient lineages defined as haplogroups. We then examined associations between common Y chromosome haplogroups and the risk of coronary artery disease in cross-sectional BHF-FHS and prospective WOSCOPS. Finally, we undertook functional analysis of Y chromosome effects on monocyte and macrophage transcriptome in British men from the Cardiogenics Study. Findings: Of nine haplogroups identified, two (R1b1b2 and I) accounted for roughly 90 of the Y chromosome variants among British men. Carriers of haplogroup I had about a 50 higher age-adjusted risk of coronary artery disease than did men with other Y chromosome lineages in BHF-FHS (odds ratio 1·75, 95 CI 1·20-2·54, p=0·004), WOSCOPS (1·45, 1·08-1·95, p=0·012), and joint analysis of both populations (1·56, 1·24-1·97, p=0·0002). The association between haplogroup I and increased risk of coronary artery disease was independent of traditional cardiovascular and socioeconomic risk factors. Analysis of macrophage transcriptome in the Cardiogenics Study revealed that 19 molecular pathways showing strong differential expression between men with haplogroup I and other lineages of the Y chromosome were interconnected by common genes related to inflammation and immunity, and that some of them have a strong relevance to atherosclerosis. Interpretation: The human Y chromosome is associated with risk of coronary artery disease in men of European ancestry, possibly through interactions of immunity and inflammation. Funding: British Heart Foundation; UK National Institute for Health Research; LEW Carty Charitable Fund; National Health and Medical Research Council of Australia; European Union 6th Framework Programme; Wellcome Trust. © 2012 Elsevier Ltd.
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk
- Authors: Charchar, Fadi
- Date: 2011
- Type: Text , Journal article
- Relation: Nature Vol. 478, no. 7367 (2011), p. 103-109
- Full Text: false
- Reviewed:
- Description: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140mmg Hg systolic blood pressure ≥90mmg Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3 GUCY1B3, NPR3 C5orf23, ADM, FURIN FES, GOSR2, GNAS EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention. © 2011 Macmillan Publishers Limited. All rights reserved. Please note that there are two hundred and six authors for this article therefore only the Federation University Australia affiliate is provided in this record.
- Description: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140mmg Hg systolic blood pressure ≥90mmg Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3 GUCY1B3, NPR3 C5orf23, ADM, FURIN FES, GOSR2, GNAS EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention. © 2011 Macmillan Publishers Limited. All rights reserved. Please note that there are two hundred and six authors for this article and we have included only the University of Ballarat Affiliate.
The acute effects of intense cardiorespiratory exercise on human telomerase reverse transcriptase and sirtuin 6 expression in white blood cells
- Authors: Chilton, Warrick , Marques, Francine , O'Brien, Brendan , Charchar, Fadi
- Date: 2012
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 30, no. e-Supplement (September 2012), p. e49
- Full Text: false
- Reviewed:
- Description: Background: Compelling epidemiological data demonstrates that regular physical exercise reduces cardiovascular mortality. Telomeres are specialised DNA structures located at the end of linear chromosomes where they protect them from degradation during DNA replication. Telomerase reverse transcriptase (TERT) expression is essential for telomere length maintenance. Accelerated telomere shortening is associated with increased risk of cardiovascular disease (CVD). Sirtuin 6 (SIRT6) is associated with increased longevity and protection against cardiac hypertrophy. Importantly, SIRT6 maintains genomic stability by specifically associating with telomeric chromatin. We hypothesized that acute cardiorespiratory exercise will affect the immediate expression of TERT and SIRT6. Methods: Twenty four healthy adults (19-39 years old) undertook 30 minutes of continuous treadmill running at 80% of maximal oxygen uptake (VO2max). Blood samples were taken before and immediately after exercise. Total RNA was extracted from white blood cells using TRIzol(R) LS reagent. TERT and SIRT6 mRNA expression were measured by real-time PCR. Results: There was no difference in TERT (P = 0.13) and SIRT6 (P = 0.73) mRNA levels immediately after acute cardiorespiratory exercise. Resting TERT levels, however, were negatively correlated with body mass index (BMI) (P = 0.03), waist to hip ratio (P = 0.01) and diastolic blood pressure (BP) (P = 0.05), while a marginal negative correlation was observed with systolic BP (P = 0.07). Conclusions: The results indicate that intense cardiorespiratory exercise does not result in acute modulation of TERT and SIRT6 mRNA. The negative correlations between BP, BMI, waist to hip ratio and TERT levels may provide a mechanistic insight into the established negative correlations between telomere length, hypertension and obesity.
- Description: C1