Concerns about the application of resistance exercise with blood-flow restriction and thrombosis risk in hemodialysis patients.

BACKGROUND: Hemodialysis (HD) per se is a risk factor for thrombosis. Considering the growing body of evidence on blood-flow restriction (BFR) exercise in HD patients, identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training model. The aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise (RE) with BFR on this molecule. METHODS: Two hundred and six HD patients volunteered for this study (all with a glomerular filtration rate of <15 mL/min/1.73 m2). The RE + BFR session consisted of 50% arterial occlusion pressure during 50 min sessions of HD (intradialytic exercise). RE repetitions included concentric and eccentric lifting phases (each lasting 2 s) and were supervised by a strength and conditioning specialist. RESULTS: Several variables were associated with elevated levels of D-dimer, including higher blood glucose, citrate use, recent cardiovascular events, recent intercurrents, higher inflammatory status, catheter as vascular access, older patients (>70 years old), and HD vintage. Furthermore, RE + BFR significantly increases D-dimer after 4 h. Patients with borderline baseline D-dimer levels (400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range (≥500 ng/mL). CONCLUSION: These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE + BFR. D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE + BFR.

Evaluation of the effects of the recommended oral dose of diflubenzuron on bovine sperm and oocyte quality using CASA and OPU-IVEP.

Introduction: The aim of this study was to evaluate potential effects of diflubenzuron on the production and quality of gametes, and on in vitro embryo production (IVEP) outcomes, in cattle. Methods: Two experiments were performed, the first to evaluate effects on semen, and the second on cumulus-oocyte complexes (COC) and on IVEP. Nelore (Bos taurus indicus) bulls (n = 14) or heifers (n = 16) were allocated into control (CG) or treatment (DIF) groups. All groups received a mineral mix supplement added (DIF) or not (CG) with diflubenzuron (30 mg/head/day), during 8 weeks. Animals were weighed and blood samples were collected throughout the experimental period. Every other week, bulls were subjected to semen collection and heifers to transvaginal ultrasound-guided follicle aspiration sessions. Semen underwent physical and morphological evaluation, and samples were stored for further computer-assisted sperm analysis. The COC recovered were evaluated according to morphology and those classified as viable were sent to an IVEP laboratory. Results: Diflubenzuron had no effect (P > 0.05) on average body weight or in any blood hematological or biochemical endpoints, regardless of gender. In experiment 1, there was no difference (P > 0.05) between DIF and CG groups for sperm concentration, morphology, or kinetics. In experiment 2, there was also no effect of diflubenzuron on the number of total, viable, or grade I oocytes, as well as on cleavage or blastocyst rates (P > 0.05). Discussion: In summary, the oral administration of diflubenzuron, within the recommended dose, has no short-term negative effects on sperm production and quality or on oocyte yield and developmental potential in vitro, in cattle.

Expanding the Toolbox for Functional Genomics in Fonsecaea pedrosoi: The Use of Split-Marker and Biolistic Transformation for Inactivation of Tryptophan Synthase (trpB) Gene.

Chromoblastomycosis (CBM) is a disease caused by several dematiaceous fungi from different genera, and Fonsecaea is the most common which has been clinically isolated. Genetic transformation methods have recently been described; however, molecular tools for the functional study of genes have been scarcely reported for those fungi. In this work, we demonstrated that gene deletion and generation of the null mutant by homologous recombination are achievable for Fonsecaea pedrosoi by the use of two approaches: use of double-joint PCR for cassette construction, followed by delivery of the split-marker by biolistic transformation. Through in silico analyses, we identified that F. pedrosoi presents the complete enzymatic apparatus required for tryptophan (trp) biosynthesis. The gene encoding a tryptophan synthase trpB -which converts chorismate to trp-was disrupted. The ΔtrpB auxotrophic mutant can grow with external trp supply, but germination, viability of conidia, and radial growth are defective compared to the wild-type and reconstituted strains. The use of 5-FAA for selection of trp- phenotypes and for counter-selection of strains carrying the trp gene was also demonstrated. The molecular tools for the functional study of genes, allied to the genetic information from genomic databases, significantly boost our understanding of the biology and pathogenicity of CBM causative agents.

In-Vitro Growth Kinetics of Mesenchymal Stem Cells in Cytotoxicity Tests Using Low-Diluted Viscum Album.

INTRODUCTION: The use of mesenchymal stem cells (MSC) in cytotoxicity tests is an in-vitro alternative model for predicting initial doses. Homeopathic medicines may stimulate the immune system to combat a pathology effectively and have been used for over two centuries. Viscum album (VA) extracts are widely used in the treatment of cancer, due to their immunomodulatory, cytotoxic and pro-apoptotic properties. OBJECTIVE: This study aimed to evaluate the in-vitro growth kinetics of canine MSC in relation to cytotoxicity, cell differentiation and expression of pluripotentiality markers, using a VA preparation at the D1D2 (1×10-1, 1×10-2 potency (VAD1D2). METHODS: MSC were obtained from adipose tissue sampled from a healthy dog that was undergoing an elective veterinary procedure and with its owner's permission. The experiments were performed in three groups: MSC treated with VAD1D2 or diluent or untreated (control). The cytotoxicity was evaluated by MTT assay. The differentiation was induced in three lineages, and apoptotic cell labeling was performed by an Annexin-V test. RESULTS: At the concentration of 10 µL/mL of VA, the number of cells after in-vitro culture was maintained when compared with the control (untreated) group. A significant and gradual decrease in cell viability was recorded as VA concentrations increased. The apoptosis analysis showed that VA at 20 µL/mL presented absolute percentages of initial apoptosis twice as high as at 10 µL/mL, which was similar to the control (untreated group). CONCLUSION: The results suggest that the use of efficient methods to assess the in-vitro cytotoxicity of VA-based homeopathic medicines using MSC lineages may predict the potential action at different concentrations. These findings demonstrated that VAD1D2 interferes with canine MSC growth kinetics.

Could sarcopenia-related mortality in end-stage renal disease be underpinned by the number of hospitalizations and cardiovascular diseases?

PURPOSE: To investigate the association between sarcopenia with the number of all-cause mortality, hospitalizations, and cardiovascular diseases in patients with end-stage renal disease (ESRD). METHODS: 247 patients with ESRD (women, n = 97) (66.6 ± 3.53 years) participated in this study. At baseline, all participants were measured with dual-energy X-ray absorptiometry and handgrip dynamometer and were prospectively followed up for 5 years. The European Working Group on Sarcopenia in Older People guidelines were utilized for Sarcopenia determination. Cox proportional hazard analysis adjusted for established risk factors was used to quantify the risk between Sarcopenia and all-cause mortality. RESULTS: Sixty-five participants (26%) were determined to have Sarcopenia at baseline and 38 (15%) have died during the follow-up. At baseline, Participants with Sarcopenia had lower body mass index and fat-free mass index. Moreover, through the 5-year follow-up, sarcopenic patients had higher number of cardiovascular disease (56.9% vs. 12.6%) and hospitalizations (93.8% vs. 49.5%) (all P < 0.0001). Sarcopenia was associated with significantly higher risk of mortality, [Hazard ratio = 3.3, (95% CI: 1.6-6.9), P = 0.001]. CONCLUSION: Sarcopenia may be a risk factor for hospitalizations, cardiovascular diseases, and all-cause mortality in patients with ESRD. These results provide support of the relevance in assessing sarcopenia in the clinical practice of chronic kidney disease and how muscle mass and strength may negatively impact the daily life of ESRD patients undergoing hemodialysis. Greater efforts at preventing muscle wasting and malfunctioning are needed through the worldwide healthcare system.

MicroRNA levels in hemodialysis patients following resistance training: Associations with functional performance, inflammatory profile, sestrins-2, and nitric oxide.

OBJECTIVE: Investigate the effects of long-term resistance training (RT) on expression of the four selected microRNAs (miRNA or mir) and further association with biomarkers related to functional performance in older end-stage renal disease (ESRD) patients undergoing hemodialysis. METHODS: Twenty-five older hemodialysis patients (glomerular filtration rate <15 mL/min/1.73 m2 aged 68.28 ± 1.06) were recruited for the study. Patients were allocated to two groups (control, n = 12 and RT, n = 13). The RT group completed 24 weeks of training, with sessions held three times per week on alternate days. Blood samples were collected pre- and post- intervention for miRNA and biochemical assays. Results were considered significant at P < 0.05. RESULTS: RT promoted benefits in inflammatory profile, nitric oxide, sestrins-2, anthropometric data, and functional performance. Trained subjects presented a 51% decrease in miRNA-31 after intervention. In addition, miRNA-1 increased 128% after RT protocol. miRNA-1 significantly correlated with functional performance, inflammatory profile, sestrins-2, and nitric oxide (all P < 0.05). CONCLUSIONS: These results suggest that the upregulation of miRNA-1 could be associated with physiological benefits promoted by RT in hemodialysis patients, providing novel understanding for potential regulatory miRNA effects on physiological RT response. These findings might point out to strategic direction for future studies.

Metabolic and hormonal responses to chronic blood-flow restricted resistance training in chronic kidney disease: a randomized trial.

Maintenance of glycemic and lipemic homeostasis can limit the progression of diabetic kidney disease. Resistance training (RT) is effective in controlling glycemia and lipemia in kidney disease; however, the effect of RT with blood flow restriction (RT+BFR) on these metabolic factors has not been investigated. We aimed to verify if chronic (6 months) RT and RT+BFR performed by patients with stage-2 chronic kidney disease (CKD) improves their glycemic homeostasis and immunometabolic profiles. Patients with CKD under conservative treatment (n = 105 (33 females)) from both sexes were randomized into control (n = 35 (11 females); age 57.6 ± 5.2 years), RT (n = 35 (12 females); age 58.0 ± 6.2 years), and RT+BFR (n = 35 (10 females); 58.0 ± 6.4 years) groups. Chronic RT or RT+BFR (6 months) was performed 3 times per week on non-consecutive days with training loading adjusted every 2 months, RT 50%-60%-70% of 1RM, and RT+BFR 30%-40%+50% of 1RM and fixed repetition number. Renal function was estimated with the glomerular filtration rate and serum albumin level. Metabolic, hormonal, and inflammatory assessments were analyzed from blood samples. Six months of RT and RT+BFR were similarly effective in improving glucose homeostasis and hormone mediators of glucose uptake (e.g., irisin, adiponectin, and sirtuin-1), decreasing pro-inflammatory and fibrotic proteins, and attenuating the progression of estimated glomerular filtration rate. Thus, RT+BFR can be considered an additional exercise modality to be included in the treatment of patients with stage 2 chronic kidney disease. Trial registration number: U1111-1237-8231. URL: http://www.ensaiosclinicos.gov.br/rg/RBR-3gpg5w/, no. RBR-3gpg5w. Novelty: Glycemic regulation induced by resistance training prevents the progression of CKD. Chronic RT and RT+BFR promote similar changes in glycemic regulation. RT and RT+BFR can be considered as non-pharmacological tools for the treatment of CKD.

Renoprotection Induced by Aerobic Training Is Dependent on Nitric Oxide Bioavailability in Obese Zucker Rats.

Aerobic training (AT) promotes several health benefits that may attenuate the progression of obesity associated diabetes. Since AT is an important nitric oxide (NO-) inducer mediating kidney-healthy phenotype, the present study is aimed at investigating the effects of AT on metabolic parameters, morphological, redox balance, inflammatory profile, and vasoactive peptides in the kidney of obese-diabetic Zucker rats receiving L-NAME (N(omega)-nitro-L-arginine methyl ester). Forty male Zucker rats (6 wk old) were assigned into four groups (n = 10, each): sedentary lean rats (CTL-Lean), sedentary obese rats (CTL-Obese), AT trained obese rats without blocking nitric oxide synthase (NOS) (Obese+AT), and obese-trained with NOS block (Obese+AT+L-NAME). AT groups ran 60 min in the maximal lactate steady state (MLSS), five days/wk/8 wk. Obese+AT rats improved glycemic homeostasis, SBP, aerobic capacity, renal mitochondria integrity, redox balance, inflammatory profile (e.g., TNF-α, CRP, IL-10, IL-4, and IL-17a), and molecules related to renal NO- metabolism (klotho/FGF23 axis, vasoactive peptides, renal histology, and reduced proteinuria). However, none of these positive outcomes were observed in CTL-Obese and Obese+AT+L-NAME (p < 0.0001) groups. Although Obese+AT+L-NAME lowered BP (compared with CTL-Obese; p < 0.0001), renal damage was observed after AT intervention. Furthermore, AT training under conditions of low NO- concentration increased signaling pathways associated with ACE-2/ANG1-7/MASr. We conclude that AT represents an important nonpharmacological intervention to improve kidney function in obese Zucker rats. However, these renal and metabolic benefits promoted by AT are dependent on NO- bioavailability and its underlying regulatory mechanisms.

Does the Combined Effect of Resistance Training with EPO and Iron Sulfate Improve Iron Metabolism in Older Individuals with End-Stage Renal Disease?

We sought to investigate the effects of resistance training (RT) combined with erythropoietin (EPO) and iron sulfate on the hemoglobin, hepcidin, ferritin, iron status, and inflammatory profile in older individuals with end-stage renal disease (ESRD). ESRD patients (n: 157; age: 66.8 ± 3.6; body mass: 73 ± 15; body mass index: 27 ± 3), were assigned to control (CTL; n: 76) and exercise groups (RT; n: 81). The CTL group was divided according to the iron treatment received: without iron treatment (CTL-none; n = 19), treated only with iron sulfate or EPO (CTL-EPO or IRON; n = 19), and treated with both iron sulfate and EPO (CTL-EPO + IRON; n = 76). The RT group followed the same pattern: (RT-none; n = 20), (RT-EPO or IRON; n = 18), and (RT-EPO + IRON; n = 86). RT consisted of 24 weeks/3 days per week at moderate intensity of full-body resistance exercises prior to the hemodialysis section. The RT group, regardless of the iron treatment, improved iron metabolism in older individuals with ESRD. These results provide some clues on the effects of RT and its combination with EPO and iron sulfate in this population, highlighting RT as an important coadjutant in ESRD-iron deficiency.

Effects of pre-dialysis resistance training on sarcopenia, inflammatory profile, and anemia biomarkers in older community-dwelling patients with chronic kidney disease: a randomized controlled trial.

BACKGROUND: Sarcopenia and chronic kidney disease (CKD) have been associated with negative outcomes in older people, including inflammatory profile and anemia biomarkers. AIMS: To investigate the effects of pre-dialysis resistance training (RT) on sarcopenia, inflammatory profile, and anemia biomarkers in older patients with CKD. METHODS: A total of 107 patients with CKD (65.4 ± 3.7 years) were randomly allocated into four groups: sarcopenic RT (n = 37), non-sarcopenic RT (n = 20), sarcopenic control (n = 28), and non-sarcopenic control (n = 22). DXA and handgrip strength were used to classify sarcopenia according to EWGSOP-2. Treatment groups underwent a 24-week intervention with RT before each dialysis session, three times per week. Blood sample analysis for ferritin, hepcidin, iron availability, and inflammatory profile (TNFα, IL-6, and IL-10) was conducted. All-cause mortality was recorded over 5 years. RESULTS: Sarcopenic RT group increased iron availability after the intervention, while their counterparts decreased. Ferritin and hepcidin significantly decreased in sarcopenic RT group. RT elicited a reduction in both TNFα and IL-6, while increasing IL-10 in both intervention groups. The rate of sarcopenic subjects substantially decreased after the intervention period (from 37 to 17 in the RT group; p = 0.01). The proportion of deaths was higher (P = 0.033) for sarcopenic subjects (Controls 35.7% vs RT 29.7%) when compared to non-sarcopenic subjects (Controls 18% vs RT 10%). The proportion of deaths decreased according to the randomization group (X2 = 8.704; P < 0.1). CONCLUSIONS: The 24-week RT intervention elicited a better sarcopenia status, better inflammatory profile, and improved anemia biomarkers. Sarcopenia was associated with higher mortality rate in older patients with CKD.

Biomarkers and Redox Balance in Aging Rats after Dynamic and Isometric Resistance Training.

Aging muscle is prone to sarcopenia and its associated telomere shortening and increased oxidative stress. Telomeres are protected by a shelterin protein complex, proteins expressed in response to DNA damage. Aerobic exercise training has shown to positively modulate these proteins while aging, but the effects of resistance training are less clear. This investigation was to examine the role of dynamic and isometric RT on markers of senescence and muscle apoptosis: checkpoint kinase 2, 53 kDa protein, shelterin telomere repeat binding 1 and 2, DNA repair, telomere length and redox state in the quadriceps muscle. Fifteen 49-week-old male rats were divided into three groups: control, dynamic resistance training, and isometric resistance training. Dynamic and isometric groups completed five sessions per week during 16 weeks at low to moderate intensity (20-70% maximal load). Only dynamic group decreased expression of 53 kDa protein, proteins from shelterin complex, oxidative stress, and improved antioxidant defense. There was no difference among groups regarding telomere length. In conclusion, dynamic resistance training was more effective than isometric in reducing markers of aging and muscle apoptosis in elderly rats. This modality should be considered as valuable tool do counteract the deleterious effects of aging.

Reduction of Management Costs and Avoidance of Air Release of Carcinogens Through a Waste Segregation Program in a Brazilian Medical Institution.

Hospital waste management is a current sustainability challenge. Although not always performed, the most applied approach in current protocols is the proper segregation of waste. The incineration of hospital waste is an significant source of emission of specific toxic particles and gases. We highlighted dioxins, whose representatives have been considered carcinogenic agents since 1994. Several experimental and epidemiologic studies have shown greater cancer morbidity and mortality associated with dioxin exposure. In the present study, we presented the impact of a hospital waste management program implemented in an oncology institution based on proper segregation and consequent reduction of incinerated mass. Data were collected for 8 years and the waste was separated into five categories: infectious (A4), chemical (B), recyclable (DR), non-recyclable (DNR), and sharps (E). The classes addressed to incineration were A4, B, and E. A team education starting from the admission process and with a continued education program was essential for a successfully implemented program. We achieved a 66% saving of waste from incineration, equivalent to 76 tons, of which 71.9 tons corresponded to recyclable waste. If the waste separation protocol was not implemented, the biohazardous and chemical material would contaminate the rest of the residues, making incineration as a final destination mandatory for all the waste. This scenario would result in significantly more dioxins release and a 64% higher cost of waste management. This low-cost implementation measure was effective in the cost reduction of waste management and minimization of air release of human carcinogens.

Clock Genes, Inflammation and the Immune System-Implications for Diabetes, Obesity and Neurodegenerative Diseases.

Inflammation is a common feature of several diseases, including obesity, diabetes and neurodegenerative disorders. Circadian clock genes are expressed and oscillate in many cell types such as macrophages, neurons and pancreatic ß cells. During inflammation, these endogenous clocks control the temporal gating of cytokine production, the antioxidant response, chemokine attraction and insulin secretion, among other processes. Deletion of clock genes in macrophages or brain-resident cells induces a higher production of inflammatory cytokines and chemokines, and this is often accompanied by an increased oxidative stress. In the context of obesity and diabetes, a high-fat diet disrupts the function of clock genes in macrophages and in pancreatic ß cells, contributing to inflammation and systemic insulin resistance. Recently, it has been shown that the administration of natural and synthetic ligands or pharmacological enhancers of the circadian clock function can selectively regulate the production and release of pro-inflammatory cytokines and improve the metabolic function in vitro and in vivo. Thus, a better understanding of the circadian regulation of the immune system could have important implications for the management of metabolic and neurodegenerative diseases.

Sprint and endurance training in relation to redox balance, inflammatory status and biomarkers of aging in master athletes.

PURPOSE: Studies have shown a positive influence of intense athletic training on several biomarkers of aging, but it remains unclear whether this influence is dependent of exercise-training-mode. This study compared redox balance, cytokine levels and biomarkers of aging between master sprinters and endurance athletes, as well as in young and middle-aged individuals as controls. METHODS: Participants were male master sprinters (SA, 50 ± 8.9yrs; n = 13) and endurance runners (EA, 53 ± 8.2yrs; n = 18) with remarkable athletic experience (~25yrs of practice), besides untrained young (YC, 22.7 ± 3.9yrs; n = 17) and age-matched controls (MC, 45.5 ± 9.8yrs; n = 12). Anamnesis, anthropometrics, biomarkers of aging, inflammation status and oxidative stress parameters were analyzed in all participants. RESULTS: An increased pro-oxidant activity (elevated protein carbonyl; isoprostanes and 8-OHdG) was observed for MC in comparison to remaining groups (p < 0.05). However, SA presented a better antioxidant capacity than both MC and EA, while nitrite/nitrate (NOx) availability was higher for EA and lower for the MC (p < 0.05). Both groups of athletes presented a better anti-inflammatory status than MC (increased IL-10 and lowered IL-6, sIL-6R, sTNF-RI), but worse than YC (increased TNF-α, sTNF-RI, and sIL-6R) (p < 0.05). Telomere length was shorter in MC, which also had lower levels of irisin and klotho, and elevated FGF-23 (p < 0.05). ADMA levels were higher in MC and SA, while irisin was lower in EA when compared to SA and YC (p < 0.05). CONCLUSION: Master athletes presented better redox balance and inflammatory status, with decreased biomarkers of aging compared to control. Regarding exercise mode, a better NO- profile, as a marker of endothelial function, was observed for EA, whereas SA had a better redox balance, cytokines profile and attenuated biomarkers of aging.

Faster and Healthier: Relationship between Telomere and Performance in Master Athletes.

Aging is associated with increased oxidative stress, chronic inflammation, and decreased telomere length (TL). However, the lifestyle of master athletes can lead to a reduced risk of these conditions, and thus attenuates aging and performance deterioration. We aimed to analyze the relationships between TL and relative performance (RP), and their relation to adiposity, oxidative stress, and inflammation in endurance (END) and sprint/power (SPW) master athletes (MAs). Twenty-two world-class MAs visited the laboratory for anamnesis, anthropometrics, and blood sampling. Inflammatory and oxidative stress parameters were assessed using commercial kits. Relative TL was determined in leukocytes through qPCR analyses. A positive association was observed between RP and TL in both groups (SPW: r=0.641; END: r=0.685) and the whole sample (r=0.594). The IL6/IL10 ratio presented an inverse correlation with RP in the whole sample (r=-0.580). Body mass index also demonstrated a negative correlation with TL for the END group (r=-0.690) and the whole sample analysis (r=-0.455). Moreover, the IL6/IL10 ratio was negatively associated with strength/power training hours (r=-0.464), whereas the CAT/TBARS ratio was negatively associated with aerobic training hours (r=-0.482). In conclusion, TL of MAs was associated with RP regardless of the training model (endurance or sprint/power), and inflammation and adiposity were associated with shorter telomeres.

Homoeopathic Viscum album (10-3) is More Cytotoxic to in vitro Culture of Human Breast Cancer Cell Line than to Human Mesenchymal Stem Cells

BackgroundBreast cancer has been considered a public health problem and homeopathic treatments are becoming increasingly recommended due to its ways of action and absence of adverse effects. MCF-7 is an adenocarcinoma of human breast cell line useful as preclinicalmodel to screen therapeutic agents such as ultra-diluted Viscum album, an European plant which extract is commonly used in cancer therapy. AIMS MCF-7 and mesenchymal stem cells (MSC) were used to evaluate the in vitrocytotoxicity of homoeopathic Viscum album 1x10-3(VA3X). Methodscells were cultured for 24 hours in controlled environment (37.5oC and 5% CO2) in 96-well plates. After this time, VA3X was added to the culture medium in concentrations varying from 10 to 100 L/mL.A control group was maintained with culture medium only. Cells were cultivated for 48 hours in these conditions for evaluation of cell viability by MTT assay. ResultsHigher cytotoxicity was observed in MCF-7 when compared to MSC, as the lower concentration of VA3X was capable of inducing tumor cell death and not healthy cell death. The MTT assay results were that 42 L/mL of VA3X reduced MCF-7 cells viability to 50% and 62 L/mL reduced MSC cells to the same percentage, what means that tumor cells are more sensible to VA3X than heathy cells. ConclusionViscum albumpresented higher cytotoxic action on human breast cancer cell line culture than on mesenchymal stem cells. This medicine is extensively used against cancer, and the use of the homoeopathic form of it brings new possibilities as no or fewer adverse effects would be present.(AU)

Author Correction: Resistance training regulates gene expression of molecules associated with intramyocellular lipids, glucose signaling and fiber size in old rats.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Training Performed Above Lactate Threshold Decreases p53 and Shelterin Expression in Mice.

Telomere shortening is associated to sarcopenia leading to functional impairment during aging. There are mechanisms associated with telomere attrition, as well to its protection and repair. Physical training is a factor that attenuates telomere shortening, but little is known about the effects of different exercise intensities on telomere biology. Thus, we evaluated the effects of exercise intensity (moderate vs. high-intensity domain) on gene expression of senescence markers Checkpoint kinase 2 and tumor suppressor (Chk2 and p53, respectively), shelterin telomere repeat binding 1 and 2 (Trf1/Trf2), DNA repair (Xrcc5), telomerase reverse transcriptase (mTERT) and telomere length in middle aged mice. Three groups were studied: a control group (CTL) and two groups submitted to swimming at intensities below the lactate threshold (LI group) and above the lactate threshold (HI group) for 40 and 20 min respectively, for 12 weeks. After training, the HI group showed reduction in p53 expression in the muscle, and decreased shelterin complex expression when compared to LI group. No differences were observed between groups for mTERT expression and telomere length. Thus, exercise training in high-intensity domain was more effective on reducing markers of senescence and apoptosis. The higher intensity exercise training also diminished shelterin expression, with no differences in telomere length and mTERT expression. Such results possibly indicate a more effective DNA protection for the higher-intensity exercise training.

Longer Telomere Length in Elite Master Sprinters: Relationship to Performance and Body Composition.

Emergent evidence suggests that the long-term healthy lifestyle of master athletes may attenuate aging. We compared telomere length (TL) of high-level master sprinters and non-athlete age-matched controls, and analyzed the relationships of TL with performance and body fat. Elite master sprinters (n=11; aged 50.1±9.2yrs) and healthy untrained controls (n=10; aged 45.4±10.9yrs) had blood samples collected for biochemical and biomolecular analyses. Master sprinters had longer TL, lower body fat and BMI, and a better lipid profile than age-matched controls (p<0.05). A large effect size was verified comparing TL between athletes vs. controls (Cohen's d=1.039), with a significant negative correlation between TL and performance decline per decade (r=-0.624, p<0.01) and a positive correlation of TL and actual performance level (r=0.641, p<0.01). In conclusion, TL of elite master sprinters was longer than their untrained peers, and seems to be not only a marker of health status, but also an indicator of sports longevity since both actual performance level and its decrease over years were related to TL. Further research might assess the TL of elite master endurance athletes for comparison with sprinters, and also investigate the underlying mechanisms by which the attenuation of telomere shortening occurs in master athletes.

Resistance training regulates gene expression of molecules associated with intramyocellular lipids, glucose signaling and fiber size in old rats.

Sarcopenia is a complex multifactorial process, some of which involves fat infiltration. Intramyocellular lipid (IMCL) accumulation is postulated to play a role on sarcopenia during aging, which is believed to be due alterations in glucose homeostasis in the skeletal muscle. Sarcopenia, along with intramuscular lipids, is associated with physical inactivity. Resistance training (RT) has been indicated to minimize the age-induced muscle skeletal adaptations. Thus, we aimed to investigate the effects of RT on mRNA levels of regulatory components related to intramyocellular lipid, glucose metabolism and fiber size in soleus and gastrocnemius muscles of aged rats. Old male rats were submitted to RT (ladder climbing, progressive load, 3 times a week for 12 weeks). Age-induced accumulation of IMCL was attenuated by RT, which was linked to a PPARy-mediated mechanism, concomitant to enhanced regulatory components of glucose homeostasis (GLUT-4, G6PDH, Hk-2 and Gly-Syn-1). These responses were also linked to decreased catabolic (TNF-α, TWEAK/Fn14 axis; FOXO-1, Atrogin-1 and MuRF1; Myostatin) and increased anabolic intracellular pathways (IGF-1-mTOR-p70S6sk-1 axis; MyoD) in muscles of trained aged rats. Our results point out the importance of RT on modulation of gene expression of intracellular regulators related to age-induced morphological and metabolic adaptations in skeletal muscle.