Circulating myostatin is reduced with aging in humans but not altered by short-term, high intensity training

Introduction: Ageing involves a loss of muscle mass and function. The rate of decline is associated with negative health outcomes and increased mortality (1). Muscle atrophy is observed at a predictable rate from 30 years of age (2), however maintenance of function is seen in masters athletes > 60 years of age (3). Myostatin acts as a negative regulator of muscle mass (4) and underlies hypertrophy with chronic resistance training (5) and atrophy in chronic conditions (4). Experiment 1: Declared healthy participants (n = 83, 18 - 75 years of age, 36 male, 47 female) were recruited. Body composition, metabolic rate, grip strength and 6-minute walk test were recorded. Venous blood was collected and total myostatin concentration (herein referred to as myostatin) quantified by enzyme-linked immunosorbent assay. Total myostatin was lower in females compared with males (2176.1 [135.3] vs. 2788.7 [180.2] pg.mL-1 [p = 0.007]). Stepwise regression observed that myostatin concentration is best predicted firstly by gender, then by age (r = 0.399, p = 0.02), and was not further improved by the addition of measures of metabolism, muscle mass or function. Experimental 2: A cohort of aged sedentary (SED) males (n = 14; 63.9 [5.6] years of age) and masters athletes (lifelong exerciser [LEX]; n = 10, 61.1 [5.8] years of age) completed 6 weeks of high intensity interview training (HITT). Two way ANOVA suggested no group (SED, LEX) × time (pre, post) interaction on myostatin concentration (p = 0.649), nor a main effect of time (p = 0.757), however there was a trend towards increased myostatin in the LEX group relative to SED (p = 0.083). Discussion: Loss of muscle mass and function occurs at a predictable rate from ~30 years of age, however the rate of loss differs between active and inactive populations. Here we demonstrate that total circulating myostatin decreases as age increases, and differs significantly between males and females. Total circulating myostatin negatively correlates with increasing age, however alterations in myostatin do not appear after short term training interventions. Longer term activity may alter myostatin, thus our next work will follow up experiment 2 with a 3 year longitudinal analysis

Defining muscle-invasive bladder cancer immunotypes by introducing tumor mutation burden, CD8+ T cells, and molecular subtypes

Immunotherapy, especially anti-PD-1, is becoming a pillar of modern muscle-invasive bladder cancer (MIBC) treatment. However, the objective response rates (ORR) are relatively low due to the lack of precise biomarkers to select patients. Herein, the molecular subtype, tumor mutation burden (TMB), and CD8+ T cells were calculated by the gene expression and mutation profiles of MIBC patients. MIBC immunotypes were constructed using clustering analysis based on tumor mutation burden, CD8+ T cells, and molecular subtypes. Mutated genes, enriched functional KEGG pathways and GO terms, and co-expressed network-specific hub genes have been identified. We demonstrated that ORR of immunotype A patients identified by molecular subtype, CD8+ T cells, and TMB is about 36% predictable. PIK3CA, RB1, FGFR3, KMT2C, MACF1, RYR2, and EP300 are differentially mutated among three immunotypes. Pathways such as ECM-receptor interaction, PI3K-Akt signaling pathway, and TGF-beta signaling pathway are top-ranked in enrichment analysis. Low expression of ACTA2 was associated with the MIBC survival benefit. The current study constructs a model that could identify suitable MIBC patients for immunotherapy, and it is an important step forward to the personalized treatment of bladder cancers. © 2021, The Author(s).This study was funded by the Act 211 Government of the Russian Federation (No.02.A03.21.0006) and the IIP UB RAS project (No.AAAA-A18–118020590108-7)

Circulating myostatin is reduced with aging in humans but not altered by short-term, high intensity training

Ageing involves a loss of muscle mass and function. The rate of decline is associated with negative health outcomes and increased mortality (1). Muscle atrophy is observed at a predictable rate from 30 years of age (2), however maintenance of function is seen in masters athletes > 60 years of age (3). Myostatin acts as a negative regulator of muscle mass (4) and underlies hypertrophy with chronic resistance training (5) and atrophy in chronic conditions (4). Experiment 1: Declared healthy participants (n = 83, 18 - 75 years of age, 36 male, 47 female) were recruited. Body composition, metabolic rate, grip strength and 6-minute walk test were recorded. Venous blood was collected and total myostatin concentration (herein referred to as myostatin) quantified by enzyme-linked immunosorbent assay. Total myostatin was lower in females compared with males (2176.1 [135.3] vs. 2788.7 [180.2] pg.mL-1 [p = 0.007]). Stepwise regression observed that myostatin concentration is best predicted firstly by gender, then by age (r = 0.399, p = 0.02), and was not further improved by the addition of measures of metabolism, muscle mass or function. Experimental 2: A cohort of aged sedentary (SED) males (n = 14; 63.9 [5.6] years of age) and masters athletes (lifelong exerciser [LEX]; n = 10, 61.1 [5.8] years of age) completed 6 weeks of high intensity interview training (HITT). Two way ANOVA suggested no group (SED, LEX) × time (pre, post) interaction on myostatin concentration (p = 0.649), nor a main effect of time (p = 0.757), however there was a trend towards increased myostatin in the LEX group relative to SED (p = 0.083). Discussion: Loss of muscle mass and function occurs at a predictable rate from ~30 years of age, however the rate of loss differs between active and inactive populations. Here we demonstrate that total circulating myostatin decreases as age increases, and differs significantly between males and females. Total circulating myostatin negatively correlates with increasing age, however alterations in myostatin do not appear after short term training interventions. Longer term activity may alter myostatin, thus our next work will follow up experiment 2 with a 3 year longitudinal analysis

An ethnobotanical study of medicinal plants used by local people in the lowlands of Konta Special Woreda, southern nations, nationalities and peoples regional state, Ethiopia

<p>Abstract</p> <p>Background</p> <p>Research was carried out in Konta Special Woreda (District); it is a remote area with lack of infrastructure like road to make any research activities in the area. Therefore, this research was conducted to investigate medicinal plants of the Konta people and to document the local knowledge before environmental and cultural changes deplete the resources.</p> <p>Methods</p> <p>The information was collected between October 2006 and February 2007. Interview-based field study constituted the main data collection method in which the gathering, preparation, use, previous and current status and cultivation practices were systematically investigated. The abundance, taxonomic diversity and distribution of medicinal plants were studied using ecological approach.</p> <p>Results</p> <p>A total of 120 species, grouped within 100 genera and 47 families that are used in traditional medical practices were identified and studied. The Fabaceae and Lamiaceae were the most commonly reported medicinal plants with 16 (13.3%) and 14 (12%) species, respectively. 25.4% of the total medicinal plants are collected from homegardens and the rest (74.6%) are collected from wild habitats. Of the total number of medicinal plants, 108 species (90%) were used to treat human ailments, 6 (5%) for livestock diseases and the remaining 6 (5%) were used to treat both human and livestock health problems. The major threats to medicinal plants reported include harvesting medicinal plants for firewood (24.8%) followed by fire (22.3%) and construction (19%). Of the four plant communities identified in the wild, more medicinal plant species (34) were found in community type-4 (<it>Hyparrhenia cymbaria</it>-<it>Erythrina abyssinica </it>community), which accounted for 61.8%.</p> <p>Conclusion</p> <p>Konta Special Woreda is an important area for medicinal plants and associated local knowledge; the natural vegetation being the most important reservoir for the majority of the medicinal plants. Environmental and cultural changes are in the process of threatening the resources and this signals the need for serious efforts to create public awareness so that measures are taken to conserve the medicinal plants in the natural ecosystems and other suitable environments.</p