Methylation of histone H3 at lysine 37 by Set1 and Set2 prevents spurious DNA replication.

DNA replication initiates at genomic locations known as origins of replication, which, in S. cerevisiae, share a common DNA consensus motif. Despite being virtually nucleosome-free, origins of replication are greatly influenced by the surrounding chromatin state. Here, we show that histone H3 lysine 37 mono-methylation (H3K37me1) is catalyzed by Set1p and Set2p and that it regulates replication origin licensing. H3K37me1 is uniformly distributed throughout most of the genome, but it is scarce at replication origins, where it increases according to the timing of their firing. We find that H3K37me1 hinders Mcm2 interaction with chromatin, maintaining low levels of MCM outside of conventional replication origins. Lack of H3K37me1 results in defective DNA replication from canonical origins while promoting replication events at inefficient and non-canonical sites. Collectively, our results indicate that H3K37me1 ensures correct execution of the DNA replication program by protecting the genome from inappropriate origin licensing and spurious DNA replication.

Phosphorylation of Histone H4T80 Triggers DNA Damage Checkpoint Recovery.

In response to genotoxic stress, cells activate a signaling cascade known as the DNA damage checkpoint (DDC) that leads to a temporary cell cycle arrest and activation of DNA repair mechanisms. Because persistent DDC activation compromises cell viability, this process must be tightly regulated. However, despite its importance, the mechanisms regulating DDC recovery are not completely understood. Here, we identify a DNA-damage-regulated histone modification in Saccharomyces cerevisiae, phosphorylation of H4 threonine 80 (H4T80ph), and show that it triggers checkpoint inactivation. H4T80ph is critical for cell survival to DNA damage, and its absence causes impaired DDC recovery and persistent cell cycle arrest. We show that, in response to genotoxic stress, p21-activated kinase Cla4 phosphorylates H4T80 to recruit Rtt107 to sites of DNA damage. Rtt107 displaces the checkpoint adaptor Rad9, thereby interrupting the checkpoint-signaling cascade. Collectively, our results indicate that H4T80ph regulates DDC recovery.

Adaptive responses of skeletal muscle to calcaneal tendon partial injury in rats: insights into remodeling and plasticity.

BACKGROUND: Skeletal muscle is a highly adaptive tissue, capable of responding to different physiological and functional demands, even in situations that may cause instability. OBJECTIVES: To evaluate how partial calcaneal tendon (CT) injuries affect the remodeling and plasticity of the gastrocnemius muscle over time. METHODS AND RESULTS: The study was carried out with Wistar rats randomly divided into five groups. The control group comprised animals not subjected to partial CT damage. The remaining four groups were subjected to partial CT damage and were further categorized based on the time of euthanasia: 3, 14, 28, and 55 days after injury. The gastrocnemius muscle was collected and used for gene expression analysis, zymography, flow cytometry, and morphology. The calcaneal tendon was analyzed only to verify the presence of the partial injury. RESULTS: The impact of partial CT injury on the gastrocnemius homeostasis, particularly on gene expression, was more pronounced in the 3-day group compared to the other groups, especially the control group. Cytokine profile and morphologic alterations occurred in the 55 days group when compared to the other groups. CONCLUSIONS: The data reported here suggest that partial injury can negatively affect intracellular signaling and degradation pathways, disturbing the muscular extracellular matrix regulatory mechanisms and communication with the tendon. However, skeletal muscle seems to mitigate these harmful effects in comparison with lesions that affect muscle and tendon.

Validation of clinical simulation scenarios for the teaching of soft skills in child-centered care.

Consultations with children and their families are complex and require soft skills. However, there is a gap in the medical curriculum concerning these skills, especially as encounter training is often adult-centered. We developed, validated, and applied simulation scenarios that prioritize active participation of children to train soft skills in child-centered care for undergraduate medical students. This is a methodological study to develop three scenarios and a checklist of what is expected. The content was validated by 18 experts. A pre-test was carried out for adjustments. Then, the simulations were applied and evaluated by 18 medical undergraduate students. They included the participation of 6 pediatric simulated patients aged 9-12 years trained by a drama teacher. According to the results, the scenarios and checklist proved to be valid instruments in content terms (ICV-I > 0.8). The scripts were followed by the simulated pediatric patients, but they had difficulty mimicking a hypoactive state. Some were anxious, but everyone enjoyed participating in the feedback. The simulated parents had difficulty participating and giving space to the child's speech. Participants assessed that the simulations performed as they were proposed and, after experimenting them, felt more prepared. The simulations provided an opportunity for students to practice soft skills by interacting with children in a safe environment. Using children as simulated patients is feasible but presents some challenges. Our study has expanded the ways in which children's health content can be taught. We are investigating whether this training leads to better patient outcomes in real clinical settings.

AI-Driven Discovery of SARS-CoV-2 Main Protease Fragment-like Inhibitors with Antiviral Activity In Vitro.

SARS-CoV-2 is the causative agent of COVID-19 and is responsible for the current global pandemic. The viral genome contains 5 major open reading frames of which the largest ORF1ab codes for two polyproteins, pp1ab and pp1a, which are subsequently cleaved into 16 nonstructural proteins (nsp) by two viral cysteine proteases encoded within the polyproteins. The main protease (Mpro, nsp5) cleaves the majority of the nsp's, making it essential for viral replication and has been successfully targeted for the development of antivirals. The first oral Mpro inhibitor, nirmatrelvir, was approved for treatment of COVID-19 in late December 2021 in combination with ritonavir as Paxlovid. Increasing the arsenal of antivirals and development of protease inhibitors and other antivirals with a varied mode of action remains a priority to reduce the likelihood for resistance emerging. Here, we report results from an artificial intelligence-driven approach followed by in vitro validation, allowing the identification of five fragment-like Mpro inhibitors with IC50 values ranging from 1.5 to 241 µM. The three most potent molecules (compounds 818, 737, and 183) were tested against SARS-CoV-2 by in vitro replication in Vero E6 and Calu-3 cells. Compound 818 was active in both cell models with an EC50 value comparable to its measured IC50 value. On the other hand, compounds 737 and 183 were only active in Calu-3, a preclinical model of respiratory cells, showing selective indexes twice as high as those for compound 818. We also show that our in silico methodology was successful in identifying both reversible and covalent inhibitors. For instance, compound 818 is a reversible chloromethylamide analogue of 8-methyl-γ-carboline, while compound 737 is an N-pyridyl-isatin that covalently inhibits Mpro. Given the small molecular weights of these fragments, their high binding efficiency in vitro and efficacy in blocking viral replication, these compounds represent good starting points for the development of potent lead molecules targeting the Mpro of SARS-CoV-2.

Natural Killer T-like Cells: Immunobiology and Role in Disease.

CD56+ T cells are generally recognized as a distinct population of T cells and are categorized as NKT-like cells. Although our understanding of NKT-like cells is far from satisfactory, it has been shown that aging and a number of disease situations have impacted these cells. To construct an overview of what is currently known, we reviewed the literature on human NKT-like cells. NKT-like cells are highly differentiated T cells with "CD1d-independent" antigen recognition and MHC-unrestricted cell killing. The genesis of NKT-like cells is unclear; however, it is proposed that the acquisition of innate characteristics by T cells could represent a remodeling process leading to successful aging. Additionally, it has been shown that NKT-like cells may play a significant role in several pathological conditions, making it necessary to comprehend whether these cells might function as prognostic markers. The quantification and characterization of these cells might serve as a cutting-edge indicator of individual immune health. Additionally, exploring the mechanisms that can control their killing activity in different contexts may therefore result in innovative therapeutic alternatives in a wide range of disease settings.

SURGICAL MANAGEMENT OF UPWARD FIXATION OF THE PATELLA VIA MEDIAL PATELLAR LIGAMENT DESMOTOMY IN A LOWLAND TAPIR (TAPIRUS TERRESTRIS).

Tapirs are endangered terrestrial mammals that inhabit several continents. They have anatomical similarities to horses, sharing a common ancestral lineage. This article reports the case of a 14-yr-old female lowland tapir (Tapirus terrestris) presented for intermittent lameness due to upward fixation of the patella causing extension of the limb in the caudal phase of the stride. Medial patellar desmotomy was performed under general anesthesia, correcting the problem. To date there are no reports of this condition or treatment recommendations in tapirs. An anatomical study including stifle dissection, advanced MRI, and CT was performed in a separate lowland tapir. According to the clinical case and the anatomical findings in the other lowland tapir, upward fixation of the patella may occur in the tapir, although the anatomy varies slightly from that of the horse. Because the lowland tapir does not have parapatellar cartilage or as large of a medial patellar ligament or medial trochlea of the distal femur compared to the horse, more severe disease secondary to complete or persistent upward fixation of the patella may not occur in tapirs. Rather, mild forms of the disease associated with intermittent upward fixation of the patella or delayed patellar release appear more likely in the tapir.

Type 2 and type 3 innate lymphoid cells at the maternal-fetal interface: implications in preterm birth.

BACKGROUND: Preterm birth (PTB) is one of the major causes of neonatal morbidity and mortality worldwide. It is commonly accepted that the act of giving birth is the final step in a proinflammatory signaling cascade, orchestrated by an intrauterine milieu coupled to hormonal cues. Consequently, the inflammatory process plays a pivotal role during the pathogenesis of human labor, both in term and preterm deliveries. The ability of innate lymphoid cells (ILCs) to act as pro-inflammatory mediators arose the interest to study their role in normal and pathological pregnancies. The aim of this work was to analyze the relative frequencies of ILCs subsets in pregnancy and the levels of IL-4, IL-17, IL-22, and IFN-γ as inflammatory mediators. Accordingly, we hypothesized that changes in the proportions of ILCs subpopulations could be related to preterm birth. METHODS: We analyzed 15 full-term delivery samples and six preterm delivery samples. In the full-term group (FTB) peripheral blood was taken during routine blood analysis, on 3 occasions: 1st, 2nd and 3rd trimester. After delivery, peripheral blood, cord blood and placenta were collected. In PTB group, peripheral blood samples were obtained on two occasions: before and 24 h after treatment with progesterone. We used flow cytometry to analyze ILCs in maternal peripheral blood, placenta, and cord blood samples. Maternal peripheral blood and cord blood samples were analyzed by enzyme-linked immunosorbent assay for IL-4, IL-17, IL-22, and IFN-γ plasma levels at the time of labor. RESULTS: We observed significantly increased relative frequencies of ILC2 and ILC3 in the decidua, as well as an increase of ILC2 in cord blood samples in PTB group, compared to FTB samples. We also found a decrease in IFN-γ in peripheral blood samples of the PTB group, suggesting a functional withdrawal. Additionally, IL-4, IL-17, IL-22 levels were similar in PTB and FTB groups, denoting a relevant role in mediating labor. CONCLUSION: Our results suggest that ILC2 and ILC3 play a role in PTB by mediating an inflammatory response. Further work is necessary to evaluate the importance of ILCs in the regulation of labor.

Total syntheses and antiproliferative activities of prenostodione and its analogues.

A high-yielding total synthesis of the indole alkaloid prenostodione was completed in 4 steps and 44% overall yield from 1H-indole-3-carboxylic acid. The expedient syntheses of prenostodiones containing distinct substituents at the para position of the phenyl frame underscored the scope of this methodology. The cytotoxic activities of the tert-butyl esters of prenostodione analogues were tested using six tumor cell lines. Preliminary structure-activity studies revealed the importance of the identity of the aromatic substituent at the C-4 position for cytotoxic activity. The IC50 values of these compounds were found to compare satisfactorily with those of the commercially available drugs etoposide and cisplatin. Furthermore, the compounds with, respectively, -OMe (14d) and -NO2 (14f) groups at C-4 were more selective than these control compounds in PC-3, K-562, and MCF-7 cells. Also, computational studies were carried out to determine the ADMET profiles and passive membrane permeabilities of the compounds. The results suggested the promise of 14d and 14f as hit compounds for the development of new anticancer agents.

Low Mg content on Ti-Nb-Sn alloy when in contact with eBMMSCs promotes improvement of its biological functions.

Magnesium is a metal used in the composition of titanium alloys and imparts porosity. Due to its osteoconductive, biocompatible and biodegradable characteristics, its application in the development of biomedical materials has become attractive. This study aimed to evaluate the influence of magnesium present in porous Ti-Nb-Sn alloys, which have a low elastic modulus in adhesive, osteogenic properties and the amount of reactive intracellular oxygen species released in mesenchymal stem cells derived from bone marrow equine bone (eBMMSCs). Mechanical properties of the alloy, such as hardness, compressive strength and elastic modulus, were analyzed, as well as surface morphological characteristics through scanning electron microscopy. The evaluation of magnesium ion release was performed by atomic force spectroscopy. The biological characteristics of the alloy, when in contact with the alloy surface and with the culture medium conditioned with the alloy, were studied by SEM and optical microscopy. Confirmation of osteogenic differentiation by alizarin red and detection of ROS using a Muse® Oxidative Stress Kit based on dihydroetide (DHE). The alloy showed an elastic modulus close to cortical bone values. The hardness was close to commercial Ti grade 2, and the compressive strength was greater than the value of cortical bone. The eBMMSCs adhered to the surface of the alloy during the experimental time. Osteogenic differentiation was observed with the treatment of eBMMMSCs with conditioned medium. The eBMMSCs treated with conditioned medium decreased ROS production, indicating a possible antioxidant defense potential of magnesium release.

Clinical, Laboratory and Ultrasonographic Interrelations in Giant Cell Arteritis.

OBJECTIVES: The diagnosis of giant cell arteritis (GCA) is based on the presence of clinical and laboratory features. Color-duplex sonography (CDS) may supplant the limited sensitivity of temporal artery biopsy. The aim of our work was to characterize clinical and laboratory findings in patients with positive CDS for GCA. MATERIALS AND METHODS: Retrospective study of all consecutive patients of our center fulfilling American College of Rheumatology criteria for GCA who performed CDS study between 2009-2019. Data on clinical and laboratory features were compared in two groups: with and without halo sign. RESULTS: Ninety-one patients were included. Temporal halo sign was identified in 46% of patients. Halo sign was more often present in older patients (77 ± 8 vs 73 ± 8 years, p = 0.022), associated with systemic features (58% vs 42%, p = 0.011), higher erythrocyte sedimentation rate (84 ± 26 vs 74 ± 34 mm/hour, p = 0.020), and lower hemoglobin values (10.9 ± 1.5 vs 12.1 ± 1.6 g/dL, p < 0.001). The number of patients under corticosteroids before CDS was higher in the group without halo (62% vs 33%, p = 0.005). Ischemic stroke occurred in 17 patients (19%), 76% in the vertebrobasilar territory, and stroke was associated with vertebral halo sign (p < 0.001). CONCLUSIONS: Halo sign was present in half of our patients. Previous corticosteroids treatment decreased positive CDS findings. Systemic symptoms and laboratory findings are more notorious in halo sign subgroup of patients. Stroke cases in GCA patients disproportionally affected the posterior circulation. Ultrasonography provides information about a more pronounced systemic involvement and a higher risk of major complications.

Activated double-negative T cells (CD3+CD4-CD8-HLA-DR+) define response to renal denervation for resistant hypertension.

PURPOSE: To explore the cellular immune response of patients with resistant hypertension treated with renal denervation (RDN). METHODS AND RESULTS: Twenty-three patients were included and blood samples were obtained in six timings, pre and post procedure. Response was evaluated at six-months and one year and was observed in 69.6% and 82.6% of patients, respectively. Absolute values of HLA-DR+ double negative (DN) T cells were significantly lower in the group of 'responders' at one year, and interaction between the timings were found in three T cell subsets (T CD4, T CD8 and naïve T CD8 cells), with the 'responders' tending to present with lower absolute values and little inter-timing variation. CONCLUSIONS: 'Responders' significantly present with lower absolute values of activated DN T cells and have lower and more stable values of total T CD8+, CD4+, and naïve T CD8+ cells. These cell types may be able to predict response to RDN.

Early and Late Mortality Following Discharge From the ICU: A Multicenter Prospective Cohort Study.

OBJECTIVES: To identify the frequency, causes, and risk factors of early and late mortality among general adult patients discharged from ICUs. DESIGN: Multicenter, prospective cohort study. SETTING: ICUs of 10 tertiary hospitals in Brazil. PATIENTS: One-thousand five-hundred fifty-four adult ICU survivors with an ICU stay greater than 72 hours for medical and emergency surgical admissions or greater than 120 hours for elective surgical admissions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcomes were early (30 d) and late (31 to 365 d) mortality. Causes of death were extracted from death certificates and medical records. Twelve-month cumulative mortality was 28.2% (439 deaths). The frequency of early mortality was 7.9% (123 deaths), and the frequency of late mortality was 22.3% (316 deaths). Infections were the leading cause of death in both early (47.2%) and late (36.4%) periods. Multivariable analysis identified age greater than or equal to 65 years (hazard ratio, 1.65; p = 0.01), pre-ICU high comorbidity (hazard ratio, 1.59; p = 0.02), pre-ICU physical dependence (hazard ratio, 2.29; p < 0.001), risk of death at ICU admission (hazard ratio per 1% increase, 1.008; p = 0.03), ICU-acquired infections (hazard ratio, 2.25; p < 0.001), and ICU readmission (hazard ratio, 3.76; p < 0.001) as risk factors for early mortality. Age greater than or equal to 65 years (hazard ratio, 1.30; p = 0.03), pre-ICU high comorbidity (hazard ratio, 2.28; p < 0.001), pre-ICU physical dependence (hazard ratio, 2.00; p < 0.001), risk of death at ICU admission (hazard ratio per 1% increase, 1.010; p < 0.001), and ICU readmission (hazard ratios, 4.10, 4.17, and 1.82 for death between 31 and 60 days, 61 and 90 days, and greater than 90 days after ICU discharge, respectively; p < 0.001 for all comparisons) were associated with late mortality. CONCLUSIONS: Infections are the main cause of death after ICU discharge. Older age, pre-ICU comorbidities, pre-ICU physical dependence, severity of illness at ICU admission, and ICU readmission are associated with increased risk of early and late mortality, while ICU-acquired infections are associated with increased risk of early mortality.

Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated modification.

Nucleosomes are decorated with numerous post-translational modifications capable of influencing many DNA processes. Here we describe a new class of histone modification, methylation of glutamine, occurring on yeast histone H2A at position 105 (Q105) and human H2A at Q104. We identify Nop1 as the methyltransferase in yeast and demonstrate that fibrillarin is the orthologue enzyme in human cells. Glutamine methylation of H2A is restricted to the nucleolus. Global analysis in yeast, using an H2AQ105me-specific antibody, shows that this modification is exclusively enriched over the 35S ribosomal DNA transcriptional unit. We show that the Q105 residue is part of the binding site for the histone chaperone FACT (facilitator of chromatin transcription) complex. Methylation of Q105 or its substitution to alanine disrupts binding to FACT in vitro. A yeast strain mutated at Q105 shows reduced histone incorporation and increased transcription at the ribosomal DNA locus. These features are phenocopied by mutations in FACT complex components. Together these data identify glutamine methylation of H2A as the first histone epigenetic mark dedicated to a specific RNA polymerase and define its function as a regulator of FACT interaction with nucleosomes.

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.

Synthesis and antituberculosis activity of new acylthiosemicarbazides designed by structural modification.

Acylthiosemicarbazides 8a-n were designed by structural modification of lead Compound 7. The syntheses of 8a-n involve a five-step procedure starting from carboxylic acids. Compounds 8a-n were tested against three Mycobacterium tuberculosis strains to measure their inhibitory antituberculosis activities. These activities could be explained according to the presence or absence of the chlorine substituent in the aromatic ring of the amide joined to the thiosemicarbazide core. Thiosemicarbazide derivative 8n is a candidate for the development of novel antitubercular agents. Ongoing studies are focused on exploring the mechanism by which these compounds inhibit M. tuberculosis cell growth.

The Effect of a Neuromuscular vs. Dynamic Warm-up on Physical Performance in Young Tennis Players.

Fernandez-Fernandez, J, García-Tormo, V, Santos-Rosa, FJ, Teixeira, AS, Nakamura, FY, Granacher, U, and Sanz-Rivas, D. The effect of a neuromuscular vs. dynamic warm-up on physical performance in young tennis players. J Strength Cond Res 34(10): 2776-2784, 2020-The aim of this study was to examine performance-enhancing (i.e., training) effects of a neuromuscular warm-up (NWU) compared with a dynamic WU (DWU) in young tennis players. Twenty-eight well-trained male tennis players with a mean age of 15.09 ± 1.16 years participated in this study and were assigned to either a training group performing NWU (n = 14), or a group that followed DWU (n = 15) before tennis-specific training, for 8 weeks. Pretest and posttest included: speed (5, 10, and 20 m); modified 5-0-5 change of direction (COD) test; bilateral/unilateral countermovement jump (CMJ); 2 kg overhead, forehand, and backhand-side medicine ball throw performance (MBT); serve velocity, and shoulder strength and range-of-motion (ROM) performance (i.e., internal [IR]/external [ER] rotation). Results showed that both groups, NWU and DWU, significantly improved their sprint performances (5-20 m; [p < 0.05; d = 0.83-1.32]), CMJ (bilateral and unilateral [dominant side] [p < 0.005; d = 1.27-1.59]), overhead MBT (p = 0.014; d = 1.02), and some shoulder strength (i.e., IR dominant side [D], ER D, ER/IR ratio [p < 0.05; d = 0.86-1.59]) and ROM (i.e., ER D, total ROM D [p < 0.05; d = 0.80-1.02]) values. However, the interaction effects revealed that NWU compared with DWU produced greater performance gains in most of the analyzed parameters (i.e., 5-10 m sprint, CMJ, overhead MBT, serve speed). The inclusion of an NWU characterized by a relatively low volume (∼20-35 minutes), including general mobility, core, and shoulder strength exercises, combined with neuromuscular-related exercises (e.g., plyometric and acceleration/deceleration/COD drills), can be recommended to obtain positive effects in tennis performance-related variables.

Sulfamethoxazole induces zinc changes at hippocampal mossy fiber synapses from pregnant rats.

The accumulation of intracellular ionic zinc and pharmaceutical compounds, like the antibiotic sulfamethoxazole, may contribute to various neuropathologies. Sulfamethoxazole and the drug trimethoprim, are inhibitors of enzymes involved in the synthesis of tetrahydrofolate and also of carbonic anhydrases. The inhibition of the latter enzymes, which are localized both intra- and extracellularly and have a key role in pH regulation, causes alkalinization that is associated with higher spontaneous transmitter release. Intense synaptic stimulation causes the entry of released zinc into postsynaptic neurons, through glutamate receptor channels or voltage dependent calcium channels. The aim of this study was to evaluate the effect of sulfamethoxazole (180 µM) on basal postsynaptic zinc and to compare it with that caused by two depolarizing media, containing high potassium or tetraethylammonium, which may induce long term synaptic plasticity. The studies were performed in brain slices from gestating rats, at the mossy fiber synapses from hippocampal CA3 area, using the zinc indicator Newport Green. In the presence of KCl (20 mM) and sulfamethoxazole (180 µM) the zinc signals were enhanced, unlike in tetraethylammonium (25 mM). After sulfamethoxazole the tetraethylammonium evoked zinc signal had reduced amplitude. Thus, the data suggests that sulfamethoxazole enhances transmitter release affecting synaptic zinc physiology.

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.