Serum levels of sirtuins, leptin and adiponectin in women with pregnancy-induced hypertension.

INTRODUCTION: Pregnancy-induced hypertension (PIH) and preeclampsia (PE) are associated with disturbed maternal inflammatory response, oxidative stress and vascular endothelial cell dysfunction. Obesity is one of risk factors of PE. Leptin is elevated in obesity and its level correlates positively with the amount of adipose tissue. In contrast, adiponectin levels are decreased in obesity. Sirtuins are expressed in the placenta, however their role in pregnancy-related pathology in humans is not known. AIM OF THE STUDY: The aim of our study was to measure serum concentrations of selected sirtuins, adiponectin and leptin in healthy pregnancy and in women with PIH. MATERIALS AND METHODS: The study included 70 women: 38 healthy pregnant women and 32 women with PIH. Blood samples were obtained between the 20th and 40th week of gestation. Serum levels of sirtuins 1, 3, 6, leptin and adiponectin were measured with ELISA. RESULTS: Leptin levels were significantly higher in PIH group as compared to the controls and correlated positively with BMI. Highest leptin levels were observed in women who needed a cesarean section. Levels of sirtuins 1, 3 and 6 were similar in both groups and did not correlate with BMI. CONCLUSIONS: High leptin levels in PIH women during 3rd trimester might be helpful to predict the necessity for a caesarian section. Blood levels of sirtuins 1, 3 and 6 measured after the 20th week of gestation cannot be regarded as a single diagnostic test for PIH or preeclampsia. More studies to clarify significance of sirtuins in PIH and PE development and diagnosis are needed.

Plasma levels of Sirtuin 7 are decreased in patients with essential hypertension.

BACKGROUND: Sirtuin 7 (SIRT7), as a nicotinamide adenine dinucleotide-dependent protein/histone deacetylase, has been implicated in the pathogenesis of cardiovascular diseases. However, whether SIRT7 is related to hypertension remains largely unclear. Thus, this study aims to explore the effects and correlation between SIRT7 and hypertension. METHODS: A total of 72 patients with essential hypertension and 82 controls with non-hypertension were recruited at Beijing Tongren Hospital Affiliated with Capital Medical University from July 2022 to June 2023. Plasma SIRT7 expression was measured using enzyme-linked immunosorbent assay analysis. Clinical baseline characteristics, laboratory measurements, echocardiographic data, and medical therapy were collected. RESULTS: Plasma levels of SIRT7 were lower in hypertensive patients compared with non-hypertensive patients [0.97 (0.58-1.30) vs. 1.24 (0.99-1.46) ng/mL, P < 0.001, respectively]. Furthermore, compared with the low SIRT7 group, there were lower levels of systolic blood pressure, hyperlipidemia, and the ultrasonic electrocardiogram parameters left ventricular end-diastolic diameter and left atrial in diastole in the high SIRT7 group (P < 0.05, respectively). More importantly, multivariate logistic regression analyses indicated that plasma SIRT7 was a predictor of hypertension [OR: 0.06, 95 % CI (0.02-0.19), P < 0.001]. Receiver operating characteristics curve analysis revealed that the optimal cutoff value for plasma SIRT7 levels in detecting hypertension was determined as 0.85 ng/mL with a sensitivity of 73.6 % and a specificity of 89.0 %. The area under the curve for SIRT7 was 0.821 (95 % CI, 0.751-0.878; P < 0.001). CONCLUSION: Plasma levels of SIRT7 are decreased in patients with essential hypertension, implying its potential as a biomarker for diagnosing essential hypertension..

Dynamic changes and clinical value of Sirt6 in acute coronary syndrome (ACS) patients.

This study aimed to investigate the role of Sirt6 and inflammatory cytokines in blood samples of patients with ACS. This is a retrospective randomized controlled clinical trial, a total of 30 patients from our hospital are included and divided into following two groups: control group and experimental group, and experimental group consists of 15 patients with ACS and control group consists of 15 patients with non-acute coronary syndrome. Sirt6 protein is detected by western blotting and Sirt6 mRNA is detected by real-time PCR, then inflammatory cytokines such as IL-1ß, IL-18, TnI, and CK-MB are measured by ELISA and cytokines NT-proBNP are monitored by immunofluorescence. Our outcomes show that Sirt6 protein and Sirt6 mRNA in experimental group are remarkably lower than those in control group, and IL-1ß, IL-18, TnI, CK-MB, and NT-proBNP in the experimental group are remarkably higher than those in control group. We can conclude that Sirt6 can prevent or inhibit the development of ACS and IL-1ß, IL-18, TnI, CK-MB, and NT-proBNP can accelerate the development of ACS.

Mitochondrial sirtuins genetic variations and gastric cancer risk: Evidence from retrospective observational study.

AIMS: The purpose of the present study was to analyze the role of selected polymorphisms of SIRT3 and SIRT5 in gastric carcinogenesis. METHODS: For this study, 500 blood samples of GC patients and 500 blood samples of healthy individuals were collected. Six selected polymorphisms of mitochondrial sirtuins were analyzed for analysis using Tetra-Arms PCR followed by DNA sequencing. RESULTS: Mutant allele frequencies of selected polymorphisms [rs3782116 (p < 0.0001), rs6598072 (p < 0.0001) and rs11246020 (p < 0.0001), rs938222 (p = 0.0136), rs3757261 (p = 0.0005) and rs2841511 (p = 0.0015)] were observed significant higher in GC patients vs controls. Haplotype analysis was performed, and 51 haplotypes were generated using haploview software. Among these haplotypes, eleven haplotypes were found associated with a significantly increased risk of GC. Furthermore, SNP-SNP interaction showed a significant correlation between studied SNPs and GC risk. Kaplan Meier analysis showed that mutant allele frequencies of selected polymorphisms are linked with a significant decrease in survival of GC patients CONCLUSIONS: It can be concluded that selected SNPs may be associated with enhanced risk of GC and hence can be potential prognostic markers for prognosis and predisposition of GC.

Decreased serum SIRT6 as a novel predictor of coronary artery disease.

OBJECTIVE: SIRT6 is an NAD-dependent histone deacetylase known to regulate aging, inflammation and energy metabolism, and might play an important role in atherosclerosis. However, whether it also plays a role in coronary artery disease (CAD) remains unclear. PATIENTS AND METHODS: In this study, we detected the expression of SIRT6 in serum by Western blotting. The concentrations of SIRT6 in serum specimens from 69 patients with CAD [30 with stable angina (SA) and 39 with acute coronary syndrome (ACS)] and 16 controls were analysed using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Western blotting analysis of the serum samples found that SIRT6 expression was decreased in the SA group (p=0.000) and ACS group (p=0.000) compared with the control group. Significantly lower levels of serum SIRT6 were observed in SA patients (18.80±9.14 ng/mL) and ACS patients (16.85±9.66 ng/mL) than in healthy controls (25.79±14.23 ng/mL). SIRT6 concentrations were positively correlated with other markers of CAD, such as high-density lipoprotein cholesterol (r=0.362, p<0.01) and age (r=0.265, p<0.05), and negatively correlated with blood glucose (r=-0.284, p<0.05). Multivariate logistic regression analysis demonstrated that lower SIRT6 levels were independently associated with the presence of CAD in men (OR=0.817, 95% CI 0.694-0.962, p=0.015). Receiver operating characteristic (ROC) curve analysis showed that lower serum SIRT6 could distinguish CAD patients (AUC, 0.726; 95% CI, 0.508-0.943; p=0.041) from controls. SIRT6 is found downregulated in blood vessels of atherosclerotic APOE-/- mice and human aorta arteries. CONCLUSIONS: We demonstrated that SA and ACS patients had lower serum concentrations of SIRT6. The decreased serum SIRT6 level was independently associated with the diagnosis of CAD. SIRT6 may play a cardioprotective role in CAD patients, and future research is required to address this issue.

Impact of Dietary Modifications on Plasma Sirtuins 1, 3 and 5 in Older Overweight Individuals Undergoing 12-Weeks of Circuit Training.

Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that regulate numerous pathways such as mitochondrial energy metabolism in the human body. Lower levels of these enzymes were linked to diseases such as diabetes mellitus and were also described as a result of aging. Sirtuins were previously shown to be under the control of exercise and diet, which are modifiable lifestyle factors. In this study, we analyzed SIRT1, SIRT3 and SIRT5 in blood from a subset of healthy elderly participants who took part in a 12-week randomized, controlled trial during which they performed, twice-weekly, resistance and aerobic training only (EX), the exercise routine combined with dietary counseling in accordance with the guidelines of the German Nutrition Society (EXDC), the exercise routine combined with intake of 2 g/day oil from Calanus finmarchicus (EXCO), or received no treatment and served as the control group (CON). In all study groups performing exercise, a significant increase in activities of SIRT1 (EX: +0.15 U/mg (+0.56/-[-0.16]), EXDC: +0.25 U/mg (+0.52/-0.06), EXCO: +0.40 U/mg (+0.88/-[-0.12])) and SIRT3 (EX: +0.80 U/mg (+3.18/-0.05), EXDC: 0.95 U/mg (+3.88/-0.55), EXCO: 1.60 U/mg (+2.85/-0.70)) was detected. Group comparisons revealed that differences in SIRT1 activity in EXCO and EXDC differed significantly from CON (CON vs. EXCO, p = 0.003; CON vs. EXDC, p = 0.010). For SIRT3, increases in all three intervention groups were significantly different from CON (CON vs. EX, p = 0.007; CON vs. EXDC, p < 0.001, CON vs. EXCO, p = 0.004). In contrast, differences in SIRT5-activities were less pronounced. Altogether, the analyses showed that the activity of SIRT1 and SIRT3 increased in response to the exercise intervention and that this increase may potentially be enhanced by additional dietary modifications.

The Role of Pentraxin-3, Fetuin-A and Sirtuin-7 in the Diagnosis of Prostate Cancer.

PURPOSE: Prostate canceris the most commonly diagnosed type of cancer and one of the leading causes of cancer-related death in men.Numerous efforts have been made to improve existing diagnostic methods and develop a new biomarker to identify patients with prostate cancer. In line with current literature, we preferred new serum-based biochemical markers as Pentraxin-3, Fetuin-A and Sirtuin-7 in the present study. MATERIALS AND METHODS: A total of 174 patients aged 42-76 years were included in the study. Patients with prostate cancer (n=38) were enrolled as Group 1 and patients with benign prostatic hyperplasia (n=136) as Group 2. The serum levels of Pentraxin-3, Fetuin-A and Sirtuin-7 levels were compared between the groups. RESULTS: The mean age of the patients was 61.9±7.6 years (p= .001). The mean serum Prostate Specific Antigen levels 32.0±59.6 (2.6-336) ng/mL and 10.0±11.3 (2.5-77.4) ng/mL in Group 1 and 2, respectively (p= .029). The mean serum levels of Pentraxin-3 and Fetuin-Ain Group 1 were statistically significantlydifferent from Group 2(3.3±4.4 ng/mL vs 1.8±2.4 ng/mL, p= .002 and 466.8±11.0 µg/mL vs 513.3±11.0 µg/mL,p= .041,respectively). There was no significant difference between Group 1 and 2 according to serum levels of Sirtuin-7 (12.7±8.2 ng/mL vs 12.7±12.4 ng/mL respectively, p= .145). CONCLUSION: Pentraxin-3, Fetuin-A and Sirtuin-7 may be effective in the diagnosis of prostate cancerin light of the current literature.In this study, it was found that Pentraxin-3 and Fetuin-A were significantly different in the diagnosis of prostate cancer.Larger-scale prospective studies are needed to determine the importance of Pentraxin-3 and Fetuin-A in the diagnosis of prostate cancer.

The effect of daily intake of vitamin D-fortified yogurt drink, with and without added calcium, on serum adiponectin and sirtuins 1 and 6 in adult subjects with type 2 diabetes.

BACKGROUND: Some evidence suggests indirect ameliorating effects of vitamin D in diabetes via adiponectin and sirtuins. This study aimed to evaluate the effects of daily intake of vitamin D-fortified yogurt drink, either with or without added calcium, on serum adiponectin, sirtuins (SIRT)1 and 6. METHODS: Briefly, 75 adults aged 30-60 years from both sexes with type 2 diabetes were randomly allocated to one of the three groups: (i) D-fortified-yogurt drink (DY; containing 1000 IU vitamin D and 300 mg calcium), (ii) Ca+D-fortified-yogurt drink (CDY; containing 1000 IU vitamin D and 500 mg calcium) and (iii) plain yogurt drink (PY; containing no detectable vitamin D and 300 mg calcium). All assessments were performed initially and after 12 weeks. RESULTS: A significant within-group increment in serum adiponectin concentrations was observed in both DY and CDY groups (+60.4 ± 8.6, +57.5 ± 6.4 µg/L, respectively; p < 0.001 for both). The concentrations of SIRT1 and SIRT6 had a significant within-group increment only in the CDY group (p = 0.003, p = 0.001 respectively). Being in CDY group was more favorable predictor of improvement in SIRT6 concentrations. Changes of 25(OH)D were a significant predictor of changes of adiponectin. However, this association disappeared following adjustment for changes of SIRT1. In contrast, the association between changes of 25(OH)D and HbA1c remained significant even after adjustment for SIRT1. CONCLUSIONS: Daily consumption of vitamin D-fortified yogurt drink for 12 weeks resulted in an increase in circulating concentrations of SIRT1 and SIRT6 in T2D subjects and D+Ca-fortified yogurt drink was more in favor of SIRT6 increment.

Age-related changes of human serum Sirtuin6 in adults.

BACKGROUND: Aging is a natural life process and with an aging population, age-related diseases (e.g. type 2 diabetes mellitus (T2DM), atherosclerosis-based cardiovascular diseases) are the primary mortality cause in older adults. Telomerase is often used as an aging biomarker. Detection and characterization of novel biomarkers can help in a more specific and sensitive identification of a person's aging status. Also, this could help in age-related diseases early prevent, ultimately prolonging the population's life span. Sirtuin 6 (Sirt6) - a member of the Sirtuins NAD+-dependent histone deacetylases family - is mainly intracellularly expressed, and is reported to be involved in the regulation of aging and aging-related diseases. Whether serum Sirt6 is correlated with aging and could be used as an aging biomarker is unknown. In the present study, we aimed to investigate the age-related Sirt6 changes in the serum of human adults. METHODS: Participants were divided into three groups according to age: 20-30 years (Young); 45-55 years (Middle-aged); and ≥ 70 years (Old). The Sirt6 and telomerase serum concentrations were determined by ELISA. The Sirt6 and human telomerase reverse transcriptase (hTERT) expression in vessels from amputated human lower limbs were analyzed using real-time quantitative PCR (RT-qPCR) and immunohistochemical staining. The relationships between variables were evaluated by Pearson correlation analysis. RESULTS: The Sirt6 and telomerase serum levels reduced with an increase in age. A similar tendency was observed for Sirt6 and hTERT in the vessel. Serum levels of Sirt6 were higher in females compared with males. Pearson's regression analysis revealed that the Sirt6 serum level positively correlated with telomerase (r = 0.5743) and both were significantly negatively correlated with age (r = - 0.5830 and r = - 0.5993, respectively). CONCLUSIONS: We reported a negative correlation between serum Sirt6 concentration and aging in human beings. Therefore, the Sirt6 serum level is a potential sex-specific aging marker.

Biomarkers of ageing and cardiac remodeling are associated with atrial fibrillation.

Objectives. Ageing is one of the strongest risk factors for atrial fibrillation (AF), and additional risk factors are also closely related to ageing. Remodeling is part of the pathophysiology of AF, and a possible common denominator of ageing and other AF risk factors. The aim of this study was to investigate any association between the presence of AF and the ageing biomarkers, leukocyte telomere length (LTL) and sirtuin-1 (SIRT-1), and the cardiac remodeling biomarkers Galectin-3 and sST2 in elderly myocardial infarction (MI) patients. Design. Patients were included after admission for MI. Diagnosis of AF was retrieved from medical records and classified as either history of AF before MI or new onset from admission to study inclusion. SIRT-1, sST2 and Galectin-3 were analyzed by ELISAs and LTL by qPCR. Results. In total, 299 patients were included, median age 75 years, 70.2% male. A history of AF was recorded in 38 patients and 30 patients experienced new onset AF. Higher levels of SIRT-1 were associated with lower risk of having a history of AF (OR = 0.46 (95% CI 0.26, 0.81), p = 0.007), whereas higher sST2 levels were associated with higher risk of AF (OR = 4.13 (95% CI 1.69, 10.13), p = 0.002). Results remained significant after adjustment for other AF risk factors. No significant associations with AF were found for Galectin-3 or LTL. None of the biomarkers associated with new onset AF. Conclusion. In elderly patients with MI, higher ST2 and lower SIRT-2 levels were associated with higher prevalence of AF, possibly reflecting both ageing and the remodeling phenomena in AF. Clinical trials registration: ClinicalTrials.gov (NCT01841944).

Impact of Nutrition on Short-Term Exercise-Induced Sirtuin Regulation: Vegans Differ from Omnivores and Lacto-Ovo Vegetarians.

Keywords: sirtuins; vegetarian; vegan; exercise; endurance athletes; metabolic regulation.

Serum Sirtuin 1, 3 and 6 Levels in Acute Myocardial Infarction Patients.

BACKGROUND: Sirtuins may act in many cellular processes like apoptosis, DNA repair and lipid/glucose metabolism. Experimental studies suggested some sirtuin types may have protective effects against endothelial dysfunction, atherosclerosis, cardiac hypertrophy and reperfusion injury. Data about sirtuins in acute myocardial infarction (AMI) patients are scarce. OBJECTIVES: To investigate temporal changes of serum sirtuin 1,3 and 6 levels in AMI patients; to compare the serum sirtuin 1,3 and 6 levels between AMI patients and control subjects; and to investigate the association of serum sirtuin 1,3 and 6 levels with prognostic markers of AMI. METHODS: Forty patients with AMI and 40 patients with normal coronary arteries were included. Left ventricular ejection fraction (LVEF), serum proBNP, CRP, sirtuin1, sirtuin 3 and sirtuin 6 levels were processed. Peak troponin T levels, GRACE score, first day / second day sirtuin levels were recorded of AMI patients. A p value < 0.05 was considered statistically significant. RESULTS: Serum sirtuin 1,3 and 6 levels in AMI patients were similar to those in normal coronary patients. No temporal change in serum sirtuin 1,3 and 6 levels were found in AMI course. No correlation was evident between the sirtuin levels and the following parameters: proBNP, CRP, peak troponin and LVEF. Baseline sirtuin 1 and 6 levels were positively correlated with reperfusion duration. Baseline sirtuin 3 levels were negatively correlated with GRACE score. CONCLUSION: Serum sirtuin 1,3 and 6 levels in AMI patients were similar to those in normal coronary patients. This study does not represent evidence of the possible protective effects of sirtuin1, 3 and 6 in AMI patients.

Serum Sirtuin 1, 3 and 6 Levels in Acute Myocardial Infarction Patients / Níveis de Sirtuína 1, 3 e 6 em Pacientes com Infarto Agudo do Miocárdio

Abstract Background: Sirtuins may act in many cellular processes like apoptosis, DNA repair and lipid/glucose metabolism. Experimental studies suggested some sirtuin types may have protective effects against endothelial dysfunction, atherosclerosis, cardiac hypertrophy and reperfusion injury. Data about sirtuins in acute myocardial infarction (AMI) patients are scarce. Objectives: To investigate temporal changes of serum sirtuin 1,3 and 6 levels in AMI patients; to compare the serum sirtuin 1,3 and 6 levels between AMI patients and control subjects; and to investigate the association of serum sirtuin 1,3 and 6 levels with prognostic markers of AMI. Methods: Forty patients with AMI and 40 patients with normal coronary arteries were included. Left ventricular ejection fraction (LVEF), serum proBNP, CRP, sirtuin1, sirtuin 3 and sirtuin 6 levels were processed. Peak troponin T levels, GRACE score, first day / second day sirtuin levels were recorded of AMI patients. A p value < 0.05 was considered statistically significant. Results: Serum sirtuin 1,3 and 6 levels in AMI patients were similar to those in normal coronary patients. No temporal change in serum sirtuin 1,3 and 6 levels were found in AMI course. No correlation was evident between the sirtuin levels and the following parameters: proBNP, CRP, peak troponin and LVEF. Baseline sirtuin 1 and 6 levels were positively correlated with reperfusion duration. Baseline sirtuin 3 levels were negatively correlated with GRACE score. Conclusion: Serum sirtuin 1,3 and 6 levels in AMI patients were similar to those in normal coronary patients. This study does not represent evidence of the possible protective effects of sirtuin1, 3 and 6 in AMI patients.

Resumo Fundamento: As sirtuínas podem atuar em muitos processos celulares, como a apoptose, reparo de DNA e metabolismo de lipídios e de glicose. Estudos experimentais sugeriram que alguns tipos de sirtuínas possam ter efeitos protetores contra disfunção endotelial, aterosclerose, hipertrofia cardíaca e lesão decorrente de reperfusão. Dados sobre as sirtuínas em pacientes com infarto agudo do miocárdio (IAM) são escassos. Objetivos: Avaliar as mudanças temporais dos níveis de sirtuína 1, 3 e 6 entre pacientes com IAM e indivíduos controles; investigar a associação entre os níveis de sirtuína 1, 3 e 6 e marcadores prognósticos de IAM. Métodos: Quarenta pacientes com IAM e 40 pacientes com artérias coronárias normais foram incluídos. Foram avaliados fração de ejeção do ventrículo esquerdo (FEVE), concentrações séricas de pró-BNP, proteína C-reativa, sirtuína 1, sirtuína 3 e de sirtuína 6. Pico de troponina T, escore GRACE, concentrações de sirtuínas no primeiro e no segundo dia foram registrados dos pacientes com IAM. Um valor de p<0,05 foi considerado estatisticamente significativo. Resultados: Os níveis de sirtuína 1, 3 e 6 em pacientes com IAM foram similares aos de pacientes com coronária normal. Não foram observadas mudanças temporais nos níveis de sirtuína 1, 3 e 6 no curso do IAM. Nenhuma correlação evidente foi observada dos níveis de sirtuína com os seguintes parâmetros: pró-BNP, proteína C-reativa, pico de troponina e FEVE. Níveis basais de sirtuína 1 e 6 apresentaram correlação positiva com a duração da reperfusão. Os níveis basais de sirtuína 3 correlacionaram-se negativamente com o escore GRACE. Conclusão: Os níveis de sirtuína 1, 3 e 6 em pacientes com IAM foram similares aos de pacientes com artérias coronárias normais. Este estudo não apresenta evidência de possíveis efeitos protetores da sirtuína 1, 3 e 6 em pacientes com IAM.

Endothelial SIRT6 Is Vital to Prevent Hypertension and Associated Cardiorenal Injury Through Targeting Nkx3.2-GATA5 Signaling.

RATIONALE: Endothelial dysfunction is an important determinant risk factor for the development of hypertension and its complications. Thus, identification of potential therapeutic targets for preventing endothelial dysfunction has major clinical importance. Emerging evidence indicates that epigenetic modifications are closely associated with the regulation of endothelial function. Among them, HDAC (histone deacetylase)-mediated epigenetic processes in vascular homeostasis and cardiovascular disease have attracted much attention. SIRT6 (sirtuin 6) is one member of SIRTs (class III HDAC) that are highly conserved NAD+-dependent deacetylases. OBJECTIVE: This study was designed to elucidate the role of SIRT6 in the pathogenesis of hypertension, discover the new targets of SIRT6, and explore related mechanisms on the regulation of endothelial function. METHODS AND RESULTS: The levels of endothelial SIRT6 were significantly reduced in 2 independent hypertension models: desoxycorticosterone acetate/salt-induced and Ang II (angiotensin II)-induced hypertensive mice. Utilizing genetically engineered endothelial-specific SIRT6 knockout (Cre+/SIRT6fl/fl) mice, we found that endothelial-specific deletion of SIRT6 significantly enhanced blood pressure, exacerbated endothelial dysfunction and cardiorenal injury in experimental hypertension. Functionally, SIRT6 has pleiotropic protective actions in endothelial cells, which include promoting endothelium-dependent vasodilatation and vascular NO bioavailability, reducing cellular permeability, ameliorating endothelial senescence and apoptosis, and facilitating autophagy. Mechanistically, SIRT6 induced the expression of GATA5 (GATA-binding protein 5), a novel regulator of blood pressure, through inhibiting Nkx3.2 (NK3 homeobox 2) transcription by deacetylating histone H3K9 (histone H3 lysine 9), thereby regulating GATA5-mediated signaling pathways to prevent endothelial injury. Finally, we provide direct evidence for the therapeutic potential of SIRT6 in desoxycorticosterone acetate/salt-induced hypertensive mice by overexpression of SIRT6 in vivo. CONCLUSIONS: This study for the first time demonstrates that SIRT6 prevents hypertension and its complications by maintaining endothelial function. Pharmacological targeting of SIRT6 may be an innovative therapeutic strategy for treating patients with hypertension.

Application of multivariate longitudinal models in SIRT6, FBS, and BMI analysis of the elderly.

Objective: SIRT6 is a main regulator of metabolism and lifespan and its importance has been implicated in the prevention against aging-related diseases. The objective of this study was to examine the application of multivariate longitudinal models in SIRT6, FBS, and BMI analysis in the elderly men after eight weeks concurrent training with supplementation of l-arginine (l-Arg). Methods: Thirty two elderly men with mean age of 63.09 ± 3.71 years were randomly divided into four equal-sized groups (each n = 8); Exercise + supplement (ES) group; exercise + placebo (EP) group; supplement (S) group and control (C) group. The ES and EP groups performed the eight weeks of concurrent training, three sessions per week. Group ES and group S consumed 1000 mg of l-Arg per day at 8:00 pm. Measurements of biochemical variables were done by ELISA Reader method. For analytical purposes, we used the paired sample t-test and multivariate longitudinal modeling with generalized estimating equation (GEE) methodology. All analyses have been implemented in R-3.4.1. p Values less than .05 were considered statistically significant. Results: With respect to significant association between sirt6, FBS, and BMI, this study showed that synergy effect of training and supplementation was greater than the sum of their individual effects on SIRT6 (ß = 0.79, p < .001), FBS (ß = -5.56, p = .022), and BMI (ß = -3.89; p = .041). Also exercise alone had a significantly larger effect than supplementation alone on responses. Conclusions: It can be concluded that the joint usage of concurrent training and supplement of l-Arg for elderly men could improve the metabolism and body composition.

Left ventricular hypertrophy is associated with increased sirtuin level in newly diagnosed hypertensive patients.

Background: Arterial hypertension is one of the leading causes of mortality and morbidity in general population. Sirtuin 1 (SIRT1) has diverse anti-inflammation, anti-oxidant, and anti-apopytosis effects on endothelium and is associated with endothelial aging and dysfunction. The objective of this study was to evaluate the relation of serum SIRT1 level with left ventricular hypertrophy (LVH) in newly diagnosed hypertensive patients. Methods: One hundered and twenty-five consecutive, newly diagnosed hypertensive patients were divided into two groups with regard to presence of LVH and compared to 40 healthy control subjects. LVH was determined by transthoracic echocardiography using the cube formula. Serum SIRT1 level was analyzed with enzyme-linked immunosorbent assay. Results: Serum SIRT1 level was significantly higher in patients with LVH compared to those without LVH (14.3 ± 3.9 ng/ml vs. 7.9 ± 3.6 ng/ml, ​P < 0.001) and healthy control subjects (14.3 ± 3.9 ng/ml vs 6.6 ± 2.0 ng/ml, P < 0.001). Multivariate logistic regression analysis revealed higher serum SIRT1 level independently predicted LVH in hypertensive patients (OR 1.50; 95% CI, 1.30-1.73; P < 0.001). Receiver-operating characteristic curve analysis demonstrated a cutoff value of 9.4 had a sensitivity of 90% and specificity of 74% for the prediction of LVH (AUC 0.885; 95% CI, 0.815-0.935; ​P < 0.0001). Conclusion: SIRT1 was a powerful biomarker for predicting LVH in hypertensive patients.

Alterations in the Expression of Amyloid Precursor Protein Cleaving Enzymes mRNA in Alzheimer Peripheral Blood.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in elderly populations. Changes in the expression of the Amyloid Precursor Protein (APP)-cleaving enzymes directly affect the formation of Amyloid Beta (Aß) plaques, a neuropathological hallmark of AD. OBJECTIVE: We used peripheral blood from AD patients to investigate the expression of genes related to APP-processing [(ß-site APP-cleaving enzyme 1 (BACE1), presenilin1 (PSEN1), and a disintegrin and metalloproteinase family 10 (ADAM10) and 17 (ADAM17)] and the epigenetic genes sirtuin (SIRT)1-3, which regulate Aß production. METHOD: Real-time polymerase chain reactions were performed to determine the specific mRNA levels in plasma. The mRNA levels in AD patients were compared to those in healthy persons and assessed in relation to the subjects' cognitive performance. RESULTS: BACE1 mRNA level in AD subjects was significantly higher than those of healthy controls, whereas ADAM10 level was significantly lower in the AD subjects. The SIRT1 level was significantly decreased, while that of SIRT2 was increased in AD subjects and elderly controls compared to levels in healthy young control. In addition, correlations were found between the expression levels of BACE1, ADAM10 and SIRT1 and cognitive performance scores. Total Aß (Aß40+Aß42) levels and the Aß40/Aß42 ratio were significantly increased in the AD subjects, whereas decrease in plasma Aß42 was found in AD subjects. There was a negative correlation between Aß40 or total Aß and Thai Mental State Examination (TMSE) while there was no correlation between Aß40/Aß42 ratio or Aß42 and TMSE. CONCLUSION: The present findings provide evidence and support for the potential roles of these enzymes that drive Aß synthesis and for epigenetic regulation in AD progression and development, which can possibly be considered peripheral markers of AD.

Assessment of Sirtuin 3 and Sirtuin 4 Level in Patients with Diabetes Mellitus and Periodontitis: A Clinical Study.

AIM: Periodontitis is considered as infection in periodontal supporting structure leading to tooth mobility and ulcerated periodontal pockets. The present study was conducted to assess Sirtuin 3 (SIRT 3) and SIRT 4 level in patients with diabetes mellitus (DM) and periodontitis. MATERIALS AND METHODS: The present study was conducted on 60 subjects. Subjects were divided into four groups, groups I to IV. Each group comprised of 15 subjects. In all subjects, fasting blood glucose level was assessed. Plaque index (PI), bleeding on probing (BOP), gingival index (GI), and clinical attachment level (CAL) were measured. The SIRT 3 and SIRT 4 were estimated by Western blot analysis. RESULTS: In group I, mean age was 44.13 ± 1.35 years, in group II, it was 43.53 ± 1.45 years, in group III it was 43.93 ± 1.22 years, and in group IV, it was 44.47 ± 0.74 years. The mean BOP score was significantly higher in group IV (5.74 ± 0.30) compared with group I (1.92 ± 0.44), group II (2.25 ± 0.22), and group III (5.31 ± 0.54). A statistically significant (p < 0.001) difference was observed in mean PI score in group I (2.25 ± 0.23), group II (2.26 ± 0.13), group III (4.37 ± 0.60), and group IV (3.25 ± 0.16). Mean GI score was significantly higher in group IV (8.89 ± 0.89) as compared with group I (0.78 ± 0.23), group II (0.95 ± 0.18), and group III (8.69 ± 1.13). A statistically significant difference was seen in mean CAL in group III (5.66 ± 0.64) and group IV (6.37 ± 0.30). Mean fasting blood sugar (mg/dL) in group I was 80.40 ± 13.05, in group II, it was 160.40 ± 27.20, in group III, it was 77.00 ± 12.78, and in group IV, it was 264.20 ± 53.17. The nonsignificant mean expression of SIRT 3 was seen in group I (29.20 ± 3.14), group II (29.19 ± 2.18), group III (28.89 ± 2.77), and group IV (29.59 ± 5.82). In group I, the mean level of SIRT 4 was 28.93 ± 12.55, in group II, it was 28.82 ± 9.14, in group III, it was 28.88 ± 6.03, and in group IV, it was 29.05 ± 10.68. CONCLUSION: Association of DM and periodontitis is well known. The SIRT 3 and SIRT 4 are useful indicators of glycemic level in patients with DM. CLINICAL SIGNIFICANCE: The SIRT 3 and SIRT 4 in DM show variation in their level. Early assessment may be proved beneficial in patients who are not responding to other drugs.

Functional genetic variants in the SIRT5 gene promoter in acute myocardial infarction.

Coronary artery disease (CAD) including acute myocardial infarction (AMI) is a common complex disease. To date, genetic causes for atherosclerosis remain largely unknown. It has recently been proposed that low frequency and rare genetic variants may be the main causes. Mitochondrial sirtuins, SIRT3, SIRT4 and SIRT5, function as critical regulators of mitochondrial metabolism, oxidative stress and cell survival. We speculated that altered SIRT5 level resulting from DNA sequence variants (DSVs) within SIRT5 gene regulatory regions may contribute to the CAD and AMI development. In this study, the SIRT5 gene promoter was genetically and functionally analyzed in large cohorts of AMI patients (n = 381) and healthy controls (n = 391). A total of eleven DSVs and SNPs were found. Two novel heterozygous DSVs (g.13574131C>A and g.13574287G>C) and three heterozygous SNPs [g.13573450A>G (rs573515169), g.13574110G>A (rs2804924) and g.13574259G>C (rs112443954)] were identified only in AMI patients. The DSVs and SNPs significantly decreased the transcriptional activity of the SIRT5 gene promoter in both HEK-293 and H9c2 cells (P < 0.05). Further electrophoretic mobility shift assay indicated that the SNPs significantly affected the binding of transcription factors. In contrast, the DSVs and SNPs found only in controls or in both AMI patients and controls did not significantly change the SIRT5 gene promoter activity (P > 0.05). Therefore, our data suggested that the DSVs and SNPs identified in AMI patients may change SIRT5 level by affecting activity of SIRT5 gene promoter, contributing to the AMI development as a risk factor.

Inter-individual responses to sprint interval training, a pilot study investigating interactions with the sirtuin system.

Sprint interval training (SIT) is reported to improve blood glucose control and may be a useful public health tool. The sirtuins and associated genes are emerging as key players in blood glucose control. This study investigated the interplay between the sirtuin/NAD system and individual variation in insulin sensitivity responses after SIT in young healthy individuals. Before and after 4 weeks of SIT, body mass and fat percentage were measured and oral glucose tolerance tests performed in 20 young healthy participants (7 females). Blood gene expression profiles (all 7 mammalian sirtuin genes and 15 enzymes involved in conversion of tryptophan, bioavailable vitamin B3, and metabolic precursors to NAD). NAD/NADP was measured in whole blood. Significant reductions in body weight and body fat post-SIT were associated with altered lipid profiles, NAD/NADP, and regulation of components of the sirtuin/NAD system (NAMPT, NMNAT1, CD38, and ABCA1). Variable improvements in measured metabolic health parameters were evident and attributed to different responses in males and females, together with marked inter-individual variation in responses of the sirtuin/NAD system to SIT.