Combined exercise training decreases blood pressure in OLDER women with NOS3 polymorphism providing changes in differentially methylated regions (DMRs).

The mechanisms by which the ageing process is associated to an unhealthy lifestyle and how they play an essential role in the aetiology of systemic arterial hypertension have not yet been completely elucidated. Our objective is to investigate the influence of NOS3 polymorphisms [-786T > C and (Glu298Asp)] on systolic blood pressure (SBP) and diastolic blood pressure (DBP) response, differentially methylated regions (DMRs), and physical fitness of adult and older women after a 14-week combined training intervention. The combined training was carried out for 14 weeks, performed 3 times a week, totalling 180 minutes weekly. The genotyping experiment used Illumina Infinium Global Screening Array version 2.0 (GSA V2.0) and Illumina's EPIC Infinium Methylation BeadChip. The participants were separated into SNP rs2070744 in TT (59.7 ± 6.2 years) and TC + CC (60.0 ± 5.2 years), and SNP rs17999 in GluGlu (58.8 ± 5.7 years) and GluAsp + AspAsp (61.6 ± 4.9 years). We observed an effect of time for variables BP, physical capacities, and cholesterol. DMRs related to SBP and DBP were identified for the rs2070744 and rs17999 groups pre- and decreased numbers of DMRs post-training. When we analysed the effect of exercise training in pre- and post-comparisons, the GluGlu SNP (rs17999) showed 10 DMRs, and after enrichment, we identified several biological biases. The combined training improved the SBP and DBP values of the participants regardless of the SNPs. In addition, exercise training affected DNA methylation differently between the groups of NOS3 polymorphisms.

Genome-Wide Admixture and Association Study of Serum Selenium Deficiency to Identify Genetic Variants Indirectly Linked to Selenium Regulation in Brazilian Adults.

Blood selenium (Se) concentrations differ substantially by population and could be influenced by genetic variants, increasing Se deficiency-related diseases. We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with serum Se deficiency in 382 adults with admixed ancestry. Genotyping arrays were combined to yield 90,937 SNPs. R packages were applied to quality control and imputation. We also performed the ancestral proportion analysis. The Search Tool for the Retrieval of Interacting Genes was used to interrogate known protein-protein interaction networks (PPIs). Our ancestral proportion analysis estimated 71% of the genome was from Caucasians, 22% was from Africans, and 8% was from East Asians. We identified the SNP rs1561573 in the TraB domain containing 2B (TRABD2B), rs425664 in MAF bZIP transcription factor (MAF), rs10444656 in spermatogenesis-associated 13 (SPATA13), and rs6592284 in heat shock protein nuclear import factor (HIKESHI) genes. The PPI analysis showed functional associations of Se deficiency, thyroid hormone metabolism, NRF2-ARE and the Wnt pathway, and heat stress. Our findings show evidence of a genetic association between Se deficiency and metabolic pathways indirectly linked to Se regulation, reinforcing the complex relationship between Se intake and the endogenous factors affecting the Se requirements for optimal health.

The influence of serum selenium in differential epigenetic and transcriptional regulation of CPT1B gene in women with obesity.

INTRODUCTION: The increasing prevalence of obesity has become a major health problem worldwide. The causes of obesity are multifactorial and could be influenced by dietary patterns and genetic factors. Obesity has been associated with a decrease in micronutrient intake and consequently decreased blood concentrations. Selenium is an essential micronutrient for human health, and its metabolism could be affected by obesity, especially severe obesity. This study aimed to identify differential methylation genes associated with serum selenium concentration in women with and without obesity. METHODOLOGY: Thirty-four patients were enrolled in the study and divided into two groups: Obese (Ob) n = 20 and Non-Obese (NOb) n = 14, according to the Body Mass Index (BMI). Anthropometry, body composition, serum selenium, selenium intake, and biochemical parameters were evaluated. DNA extraction and bisulfite conversion were performed to hybridize the samples on the 450k Methylation Chip Infinium Beadchip (Illumina). Bioinformatics analysis was performed using the R program and the Champ package. The differentially methylated regions (DMRs) were identified using the Bumphunter method. In addition, logarithmic conversion was performed for the analysis of serum selenium and methylation. RESULTS: In the Ob group, the body weight, BMI, fat mass, and free fat mass were higher than in the NOb group, as expected. Interestingly, the serum selenium was lower in the Ob than in the NOb group without differences in selenium intake. One DMR corresponding to the CPT1B gene, involved in lipid oxidation, was related to selenium levels. This region was hypermethylated in the Ob group, indicating that the intersection between selenium deficiency and hypermethylation could influence the expression of the CPT1B gene. The transcriptional analysis confirmed the lower expression of the CPT1B gene in the Ob group. CONCLUSION: Studies connecting epigenetics to environmental factors could offer insights into the mechanisms involving the expression of genes related to obesity and its comorbidities. Here we demonstrated that the mineral selenium might play an essential role in lipid oxidation via epigenetic and transcriptional regulation of the CPT1B gene in obesity.

14-Week exercise training modifies the DNA methylation levels at gene sites in non-Alzheimer's disease women aged 50 to 70 years.

Exercise training emerges as a key strategy in lifestyle modification, capable of reducing the risk of developing Alzheimer's disease (AD) due to risk factors such as age, family history, genetics and low level of education associated with AD. We aim to analyze the effect of a 14-week combined exercise training (CT) on the methylation of genes associated with AD in non-alzheimer's disease women. CT sessions lasted 60 min, occurring three times a week for 14 weeks. Forty non-Alzheimer's disease women aged 50 to 70 years (60.7 ± 4.1 years) with a mean height of 1.6 ± 0.1 m, mean weight of 73.12 ± 9.0 kg and a mean body mass index of 29.69 ± 3.5 kg/m2, underwent two physical assessments: pre and post the 14 weeks. DNA methylation assays utilized the EPIC Infinium Methylation BeadChip from Illumina. We observed that 14 weeks of CT led to reductions in systolic (p = 0.001) and diastolic (p = 0.017) blood pressure and improved motor skills post-intervention. Among 25 genes linked to AD, CT induced differentially methylated sites in 12 genes, predominantly showing hypomethylated sites (negative ß values). Interestingly, despite hypomethylated sites, some genes exhibited hypermethylated sites (positive ß values), such as ABCA7, BDNF, and WWOX. A 14-week CT regimen was adequate to induce differential methylation in 12 CE-related genes in healthy older women, alongside improvements in motor skills and blood pressure. In conclusion, this study suggest that combined training can be a strategy to improve physical fitness in older individuals, especially able to induce methylation alterations in genes sites related to development of AD. It is important to highlight that training should act as protective factor in older adults.

Influence of Fluid Ingestion on Heart Rate, Cardiac Autonomic Modulation and Blood Pressure in Response to Physical Exercise: A Systematic Review with Meta-Analysis and Meta-Regression.

A systematic review was undertaken to investigate the involvement of hydration in heart rate (HR), HR variability (HRV) and diastolic (DBP) and systolic (SBP) blood pressure in response to exercise. Data synthesis: The EMBASE, MEDLINE, Cochrane Library, CINAHL, LILACS and Web of Science databases were searched. In total, 977 studies were recognized, but only 36 were included after final screening (33 studies in meta-analysis). This study includes randomized controlled trials (RCTs) and non-RCTs with subjects > 18 years old. The hydration group consumed water or isotonic drinks, while the control group did not ingest liquids. For the hydration protocol (before, during and after exercise), the HR values during the exercise were lower compared to the controls (-6.20 bpm, 95%CI: -8.69; -3.71). In the subgroup analysis, "water ingested before and during exercise" showed lower increases in HR during exercise (-6.20, 95%CI: 11.70 to -0.71), as did "water was ingested only during exercise" (-6.12, 95%CI: -9.35 to -2.89). Water intake during exercise only revealed a trend of avoiding greater increases in HR during exercise (-4,60, 95%CI: -9.41 to 0.22), although these values were not significantly different (p = 0.06) from those of the control. "Isotonic intake during exercise" showed lower HRs than the control (-7.23 bpm, 95% CI: -11.68 to -2.79). The HRV values following the exercise were higher in the hydration protocol (SMD = 0.48, 95%CI: 0.30 to 0.67). The values of the SBP were higher than those of the controls (2.25 mmHg, 95%CI: 0.08 to 4.42). Conclusions: Hydration-attenuated exercise-induced increases in HR during exercise, improved autonomic recovery via the acceleration of cardiac vagal modulation in response to exercise and caused a modest increase in SBP values, but did not exert effects on DBP following exercise.

Eight Weeks of Physical Training Decreases 2 Years of DNA Methylation Age of Sedentary Women.

Purpose: The acceleration of epigenetic age is a predictor of mortality and contributes to the increase in chronic diseases. Adherence to a healthy lifestyle is a strategy to reduce epigenetic age. The present study aimed to determine whether eight weeks of combined (aerobic and strength) training (CT) can influence the epigenetic age of women between 50 and 70 years old and the differences in sites and methylated regions. Methods: Eighteen women (AARLow: lower age acceleration residual, n = 10; AARHigh: higher age acceleration residual, n = 8) participated in a combined exercise training program (60 minutes, 3× a week) for eight weeks. DNA was extracted from whole blood using the salting out technique. DNA methylation was performed using the array technique (Illumina's Infinium Methylation BeadChip 850k). We used the DNA Methylation Age Calculator platform to calculate the biological epigenetic age. Two-way ANOVA followed by FISHER LSD posthoc was Applied, adopting p < .05. Results: After eight weeks of CT, there were no changes to the epigenetic age acceleration for the AARLow group (PRE: -2.3 ± 3.2 to POST: -2.3 ± 3.6). However, the AARHigh group significantly decreased the age acceleration (PRE: 3.6 ± 2.6 to POST: 2.2 ± 2.7) (group effect, p = .01; time effect, p = .31; group vs. time effect, p = .005). Conclusion: CT for eight weeks benefits the epigenetic clock of women with the most accelerated age.

Physical training improves physical activity levels but is associated with amplification of sedentary behavior in older women.

Physical activity level (PAL) and sedentary behavior (SB) are independent predictors of mortality. It is unclear how these predictors interact with each other and health variables. Investigate the bidirectional relationship between PAL and SB, and their impact and health variables of women aged 60 to 70 years. One hundred forty-two older adults women (66.3 ± 2.9 years) considered insufficiently active were submitted to 14 weeks of multicomponent training (MT), multicomponent training with flexibility (TMF), or the control group (CG). PAL variables were analyzed by accelerometry and QBMI questionnaire, physical activity (PA) light, moderate, vigorous and CS by accelerometry, 6 min walk (CAM), SBP, BMI, LDL, HDL, uric acid, triglycerides, glucose and cholesterol total. In linear regressions, CS was associated with glucose (B:12.80; CI:9.31/20.50; p < 0.001; R2:0.45), light PA (B:3.10; CI:2, 41/4.76; p < 0.001; R2:0.57), NAF by accelerometer (B:8.21; CI:6.74/10.02; p < 0.001; R2:0.62), vigorous PA (B:794.03; CI:682.11/908.2; p < 0.001; R2:0.70), LDL (B:13.28; CI:7.45/16.75; p < 0.002; R2:0.71) and 6 min walk (B:3.39; CI:2.96/8.75; p < 0.004; R2:0.73). NAF was associated with mild PA (B:0.246; CI:0.130/0.275; p < 0.001; R2:0.624), moderate PA (B:0.763; CI:0.567/0.924; p < 0.001; R2:0.745), glucose (B:-0.437; CI:-0.789/-0.124; p < 0.001; R2:0.782), CAM (B:2.223; CI:1.872/4.985; p < 0.002; R2:0.989) and CS (B:0.253; CI: 0.189/0.512; p < 0.001; R2:1.94). The NAF can enhance CS. Build a new look at how these variables are independent but dependent simultaneously, being able to influence the quality of health when this dependence is denied.

Older postmenopausal women with lower lean mass have hypermethylated sites in the PI3K-Akt pathway.

Introduction: The decrease in lean mass is directly related to the loss of independence, muscle strength, and worse quality of life over the years. Although the genetic determinants of muscle mass were well recognized, recent literature has been uncovering new epigenetic factors affecting the state of muscular tissue. This study aimed to verify differences in the DNA methylation profile among Brazilian postmenopausal women aged 50-70 years according to the lean mass evaluation. Methods: A cross-sectional study comprised 40 women aged 50-70 years. After K-means cluster analysis the 40 participants were divided into two groups, the Lower Lean Mass group with 20 participants (61.1 ± 4.6 years) and the Higher Lean Mass group with 20 participants (60.7 ± 3.2 years). Lean mass was measured by dual-energy X-ray emission densitometry (DEXA). The participants' DNA was extracted using the Salting Out technique and subsequently, the Illumina 850k EPIC Infinium Methylation BeadChip was performed to obtain methylation data. Results: We obtained 1,913 differentially methylated sites (p ≤ 0.005 of ß > 5% and ß < -5%) in a total of 979 genes between groups (p ≤ 0.005; -5% > ß > 5%). In addition, the PI3K-Akt pathway had the greatest power of significance with an FDR of 4.6 × 10-3. Conclusion: Our results demonstrate a differentiation between specific sites of different genes, which have essential functions in body composition and energy metabolism, supporting future studies that aim to relate lean mass with epigenetics.

Association of Training in Basic Life Support with the Evolution of Cardiopulmonary Resuscitation Performed by Firefighters.

Introduction: This study aimed to compare the results of professional technical and anthropometric anamnesis data with the transmission of external chest compressions performed by military firefighters at different execution times. Objective: The objective was to evaluate the performance and perceived effort of the sequence of external chest compressions performed in two minutes, as well as the evolution of the technique over time. Materials and Methods: This was a descriptive, correlational study involving adult firefighters who were members of a specific firefighter group, comprising a population of 105 individuals with a voluntary sample of 44 participants. The study used a Bayesian statistical approach to provide probabilistic expressions. Results: The participants had an average work experience of 17 years, an average age of 38.6 years, an average weight of 81.48 kilograms, an average height of 176 centimeters, and an average of 2.5 qualifications. The results indicated that the firefighters performed external chest compressions with excellent technique and a moderate level of perceived effort in a two-minute evaluation. The evaluation of the evolution of the technique over time showed that the participants were able to maintain high-quality compressions for an average of 6 minutes, with a maximum of 20 uninterrupted minutes. Conclusion: The study underscores the critical role of professional firefighters in performing and maintaining high-quality external chest compressions, which has the potential to reduce morbidity and mortality in cases of cardiorespiratory arrest.

Negligible Effects of Nutraceuticals from Beetroot Extract on Cardiovascular and Autonomic Recovery Response following Submaximal Aerobic Exercise in Physically Active Healthy Males: A Randomized Trial.

BACKGROUND: There is little evidence that nutraceuticals from beetroot extract are beneficial with regards to recovery of the cardiovascular parameters and the autonomic nervous system (ANS) after submaximal aerobic exercise, though this formulation is employed widely for this purpose. OBJECTIVE: To study the effects of beetroot extract supplementation on the recovery of cardiorespiratory and autonomic parameters after a session of submaximal aerobic exercise. METHODS: Sixteen healthy male adults commenced a cross-over, randomized, double-blind and placebo-controlled trial. Beetroot extract (600 mg) or placebo (600 mg) were ingested 120 min prior to evaluation on randomized days. We assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial pressure (MAP), heart rate (HR) and HR variability (HRV) indexes at Rest and during 60 min of recovery from submaximal aerobic exercise. RESULTS: Beetroot extract ingestion slightly accelerated HR, SBP, DBP and MAP reduction following exercise associated to the placebo protocol (vs. rest). Yet no group effect (p = 0.99) was identified between the beetroot and placebo protocols on HR mean, in addition to interaction (group vs. time) (p = 0.60). No group effect was attained between the SBP (p = 0.90), DBP (p = 0.88), MAP (p = 0.73) and PP (p = 0.99) protocols and no significant differences (group vs. time) were observed between the values of SBP (p = 0.75), DBP (p = 0.79), MAP (p = 0.93) and PP (p = 0.63) between placebo and beetroot protocols. Similarly, the reoccurrence of cardiac vagal modulation after exercise via the HF (ms2) was enhanced, but not with regards to the RMSSD index. No group effect (p = 0.99) was identified for the HF (p = 0.90) and RMSSD (p = 0.67) indices. Likewise, we observed no significant differences (group vs. time) amongst the values of HF (p = 0.69) and RMSSD (p = 0.95) between the placebo and beetroot protocols. CONCLUSION: Whilst beetroot extract might assist the recovery of the cardiovascular and autonomic systems following submaximal aerobic exercise in healthy males, these results seem insignificant owing to minor differences between interventions and are weak clinically.

Nitrate-rich beet juice intake on cardiovascular performance in response to exercise in postmenopausal women with arterial hypertension: study protocol for a randomized controlled trial.

BACKGROUND: There is no evidence of the use of beetroot juice with a previously recommended dose of nitrate (NO3) (> 300 mg) on the cardiovascular performance during and recovery following exercise in postmenopausal women with systemic arterial hypertension (SAH). METHODS: We will investigate the effects of beetroot juice rich in NO3 acutely (800 mg) and during a week with daily doses (400 mg) on blood pressure, heart rate (HR), cardiac autonomic control, endothelial function, inflammatory, hormonal, and stress biomarkers oxidative stress and enzymes involved in nitric oxide synthesis and mitochondrial regulation, under resting conditions, as well as mediated by submaximal aerobic exercise sessions. Through a randomized, crossover, triple-blind, placebo-controlled clinical trial, 25 physically inactive women with SAH will undergo an acute and 1-week trial, each with two intervention protocols: (1) placebo and (2) beetroot, in which will ingest beet juice with or without NO3 in its composition with a 7-day washout interval. On collection days, exercise will be performed on a treadmill for 40 min at a speed corresponding to 65-70% of VO2peak. The collection of variables (cardiovascular, autonomic, and blood samples for molecular analyses) of the study will take place at rest (135 min after ingestion of the intervention), during exercise (40 min), and in the effort recovery stage (during 60 min) based on previously validated protocols. The collections were arranged so that the measurement of one variable does not interfere with the other and that they have adequate intervals between them. DISCUSSION: The results of this research may help in the real understanding of the nutritional compounds capable of generating safety to the cardiovascular system during physical exercise, especially for women who are aging and who have cardiovascular limitations (e.g., arterial hypertension) to perform physical exercise. Therefore, our results will be able to help specific nutritional recommendations to optimize cardiovascular health. TRIAL REGISTRATION: ClinicalTrials.gov NCT05384340. Registered on May 20, 2022.

Exercise training modifies the whole blood DNA methylation profile in middle-aged and older women.

This is a longitudinal single-arm clinical trial aimed to investigate whether exercise training would modify the whole blood methylation profile in healthy women. A total of 45 subjects were engaged in an exercise training protocol during a 14-wk follow up, consisting of aerobic cardiorespiratory and muscle strength exercises. Subjects were evaluated at baseline (PRE), after 7 wk of exercise training (POST 7), and after 14 wk of exercise training (POST 14). Functional primary outcomes included anthropometric, blood pressure, biochemical measurements, physical tests, and global health assessments. Blood samples were collected at each time point to determine the methylation profile using a DNA methylation array technique screening up to 850k different sites. Exercise training decreased blood pressure and triglyceride levels and enhanced physical performance, including upper- and lower-body maximum strength. Moreover, exercise training improved markers of quality of life. In the array analysis, 14 wk of exercise training changed the methylation of more than 800 sites. Across these differentially methylated sites, we found that differentially methylated sites in the promoter region were more hypermethylated after exercise training, suggesting that this hypermethylation process may affect the transcription process. When inputting the differentially methylated sites in pathway analysis, we found several metabolic pathways, including AMPK signaling, TGF-ß signaling, and insulin signaling. This study demonstrates that exercise training promotes a robust change in the whole blood methylation profile and provides new insights into the key regulators of exercise-induced benefits.NEW & NOTEWORTHY We have shown that exercise training lowers blood pressure and triglyceride levels, improves physical performance, and improves quality of life in middle-aged and elderly women. Regarding epigenetic data, we noticed that more than 800 sites are differentially methylated in whole blood after physical training. We emphasize that the differentially methylated sites in the promoter region are more hypermethylated after physical training. In addition, this study shows that key members of metabolic pathways, including AMPK signaling, TGF-ß signaling, and insulin signaling, are among the genes hypermethylated after physical exercise in older women.

14-weeks combined exercise epigenetically modulated 118 genes of menopausal women with prediabetes.

Background: Pre-diabetes precedes Diabetes Mellitus (DM) disease and is a critical period for hyperglycemia treatment, especially for menopausal women, considering all metabolic alterations due to hormonal changes. Recently, the literature has demonstrated the role of physical exercise in epigenetic reprogramming to modulate the gene expression patterns of metabolic conditions, such as hyperglycemia, and prevent DM development. In the present study, we hypothesized that physical exercise training could modify the epigenetic patterns of women with poor glycemic control. Methods: 48 post-menopause women aged 60.3 ± 4.5 years were divided according to their fasting blood glucose levels into two groups: Prediabetes Group, PG (n=24), and Normal Glucose Group, NGG (n=24). All participants performed 14 weeks of physical exercise three times a week. The Infinium Methylation EPIC BeadChip measured the participants' Different Methylated Regions (DMRs). Results: Before the intervention, the PG group had 12 DMRs compared to NGG. After the intervention, five DMRs remained different. Interestingly, when comparing the PG group before and after training, 118 DMRs were found. The enrichment analysis revealed that the genes were related to different biological functions such as energy metabolism, cell differentiation, and tumor suppression. Conclusion: Physical exercise is a relevant alternative in treating hyperglycemia and preventing DM in post-menopause women with poor glycemic control.

Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies.

Obesity is directly connected to lifestyle and has been associated with DNA methylation changes that may cause alterations in the adipogenesis and lipid storage processes contributing to the development of the disease. We demonstrate a complete protocol from selection to epigenetic data analysis of patients with and without obesity. All steps from the protocol were tested and validated in a pilot study. 32 women participated in the study, in which 15 individuals were classified with obesity according to Body Mass Index (BMI) (45.1 ± 5.4 kg/m2); and 17 individuals were classified without obesity according to BMI (22.6 ± 1.8 kg/m2). In the group with obesity, 564 CpG sites related to fat mass were identified by linear regression analysis. The CpG sites were in the promoter regions. The differential analysis found 470 CpGs hypomethylated and 94 hypermethylated sites in individuals with obesity. The most hypomethylated enriched pathwayswere in the RUNX, WNT signaling, and response to hypoxia. The hypermethylated pathways were related to insulin secretion, glucagon signaling, and Ca2+. We conclude that the protocol effectively identified DNA methylation patterns and trait-related DNA methylation. These patterns could be associated with altered gene expression, affecting adipogenesis and lipid storage. Our results confirmed that an obesogenic lifestyle could promote epigenetic changes in human DNA.