Inactivation of Myostatin Delays Senescence via TREX1-SASP in Bovine Skeletal Muscle Cells.

The myostatin (MSTN) gene also regulates the developmental balance of skeletal muscle after birth, and has long been linked to age-related muscle wasting. Many rodent studies have shown a correlation between MSTN and age-related diseases. It is unclear how MSTN and age-associated muscle loss in other animals are related. In this study, we utilized MSTN gene-edited bovine skeletal muscle cells to investigate the mechanisms relating to MSTN and muscle cell senescence. The expression of MSTN was higher in older individuals than in younger individuals. We obtained consecutively passaged senescent cells and performed senescence index assays and transcriptome sequencing. We found that senescence hallmarks and the senescence-associated secretory phenotype (SASP) were decreased in long-term-cultured myostatin inactivated (MT-KO) bovine skeletal muscle cells (bSMCs). Using cell signaling profiling, MSTN was shown to regulate the SASP, predominantly through the cycle GMP-AMP synthase-stimulator of antiviral genes (cGAS-STING) pathway. An in-depth investigation by chromatin immunoprecipitation (ChIP) analysis revealed that MSTN influenced three prime repair exonuclease 1 (TREX1) expression through the SMAD2/3 complex. The downregulation of MSTN contributed to the activation of the MSTN-SMAD2/3-TREX1 signaling axis, influencing the secretion of SASP, and consequently delaying the senescence of bSMCs. This study provided valuable new insight into the role of MSTN in cell senescence in large animals.

Growth Traits and Sperm Proteomics Analyses of Myostatin Gene-Edited Chinese Yellow Cattle.

Chinese Yellow Cattle, an ancient and domesticated breed for draft service, provide unique animal genetic resources with excellent genetic features, including crude feed tolerance, good stress resistance, strong adaptability, and tender meat quality; however, their production performance and meat yield are significantly inferior. Herein, the myostatin gene (MSTN), a negative regulator of skeletal muscle development, was knocked out by CRISPR/Cas9 technology. Eight MSTN gene-edited bull calves (MT) were born, and six of them are well-developed. Compared with the control cattle (WT), the growth trait indexes of MT cattle were generally increased, and the hindquarters especially were significantly improved. The biochemical indexes and the semen characteristics demonstrated that MT bulls were healthy and fertile. Consistent with our conjecture, the wobble and beating of MT bull spermatozoa were significantly higher than that of WT. Nine sperm motility-related proteins and nineteen mitochondrial-related proteins were identified by up-regulation in MT bull spermatozoa using FLQ proteomic technique and act to govern sperm flagellum assembly, organization, and beating and provide sufficient energy for sperm motility. The current study confirmed that the MSTN gene-edited Chinese Yellow cattle have improved growth traits and normal fertility, which can be used for beef cattle production and breeding.

[Correlation of the quality of life with the inspiratory capacity in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To evaluate the correlation of the quality of life in patients with chronic obstructive pulmonary disease (COPD) with the lung function tests, especially the inspiratory capacity (IC). METHODS: Sixty-two stable COPD patients were enrolled between Jan. 2006 and Mar. 2007 (55 males and 7 females), with an age range of 43 - 79 (66 +/- 8) years. Lung volume, spirometry and small airway function measurements were performed in all patients. The St George respiratory questionnaire (SGRQ) score was collected. Pearson's correlation coefficients were calculated. RESULTS: The total score of the 62 COPD patients was 43 +/- 17. The 3 component scores were: symptoms (54 +/- 23), activity (54 +/- 19) and impact (33 +/- 20). The FEV(1) pred% was (43 +/- 13)%, FEV(1)/FVC was (52 +/- 11)%, residual volume (RV) pred% was (194 +/- 50)%, RV/total lung capacity (TLC) was (166 +/- 31)%, and IC pred% was (74 +/- 21)%. The SGRQ scores were significantly correlated with IC pred%, RV pred%, RV/TLC, FEV(1) pred%, FEV(1)/FVC and small airway function measurements (FEF(50%), FEF(25%), MMEF). The correlation coefficients between the parameters of spirometry and the total score of SGRQ were -0.336 to -0.479, while those between the parameter of small airway function and the total score of SGRQ were -0.368 to -0.411. Among all these lung function measurements, IC pred% was best correlated with the SGRQ score, and the correlation coefficients between the IC pred% and the total score and the other 3 component scores of SGRQ were -0.418 to -0.521, respectively, P < 0.05. The symptoms section score had the poorest correlation with the lung function test. CONCLUSIONS: The lung function test results correlate with the quality of life in patients with COPD. IC pred%, together with FEV(1) pred% should be used for clinical evaluation of patients with COPD.

[Epidemiological data of chronic obstructive pulmonary disease in Yanqing County in Beijing].

OBJECTIVE: To evaluate the epidemiological characteristic and risk factors of chronic obstructive pulmonary disease (COPD) in the rural area of Beijing. METHODS: The data of 1,624 people aged more than 40 in 5 villages in Yanqing County in Beijing were collected. The habitation condition, life and cooking habit, smoking history, personal history and family history were asked, and their physical examinations and lung function tests were conducted. RESULTS: The prevalence of COPD was 9.11% in this area, 15.05% in males and 3.76% in females. There were significant differences in sex, age, smoking history, family history, frequent cough before age 14 and body index between the COPD and non-COPD groups. The prevalence of corpulmonale was 1.66% in this area. CONCLUSION: The prevalence of COPD was high in this area and related with sex, age, smoking history, family history, frequent cough before age 14 and low body index. Other factors such as environment, working exposure need to be studied in the future. COPD is a major public health problem, which should claim more attention.

[Characteristics of non-symptomatic chronic obstructive pulmonary disease patients].

OBJECTIVE: To evaluate the epidemiological characteristics of non-symptomatic chronic obstructive pulmonary disease (COPD) patients in a rural area in Beijing. METHODS: The data of 1,624 people aged more than 40 in 5 villages in Yanqing county in Beijing were collected. Information of medical history and symptom were obtained, and physical examination and lung function test were performed. RESULTS: The prevalence of COPD was 9.1% (148/1 624) in this area. In these 148 patients, 62 (42%) were non-symptomatic and 86 (58%) were symptomatic, the prevalence of non-symptomatic COPD being 3.8% (62/1 624). There was no statistical difference in the sex, age, occupation, marriage status, education level and smoking index between the symptomatic and the non-symptomatic groups (all P > 0.05). The forced expired volume in one second (FEV(1)) and FEV(1)% predicted were lower in the symptomatic group [(1.3 +/- 0.7) L, (61 +/- 23)%] than those in the non-symptomatic group [(1.5 +/- 0.6) L, (70 +/- 22)%; all P < 0.05]. CONCLUSIONS: The prevalence of COPD was high in this area with a high percentage of non-symptomatic patients. The COPD prevalence might be underestimated due to the symptom free patients.