RNA-sequencing reveals a gene expression signature in skeletal muscle of a mouse model of age-associated post-operative functional decline

This study aimed to characterize the effects of laparotomy on post-operative physical function and skeletal muscle gene expression in C57BL/6N mice at 3, 20 and 24 months of age to investigate late-life vulnerability and resiliency to acute surgical stress. Pre- and post-operative physical functioning were assessed by forelimb grip strength and motor coordination. Laparotomy induced an age-associated post-operative decline in forelimb grip strength that was greatest in the oldest mice. In contrast, while motor coordination declined with increasing age at baseline, it was unaffected by laparotomy. Moreover, baseline physical function as stratified by motor coordination performance (low vs. high functioning) in 24-month-old mice did not differentially affect post-laparotomy reduction in grip strength. RNA sequencing of soleus muscles showed that laparotomy induced age-associated differential gene expression and canonical pathway activation with the greatest effects in the youngest mice. Examples of such age-associated, metabolically important pathways that were only activated in the youngest mice after laparotomy included oxidative phosphorylation and NRF2-mediated oxidative stress response. Analysis of lipid mediators in serum and gastrocnemius muscle showed alterations in profiles of these mediators during aging and confirmed an association between such changes and functional status in gastrocnemius muscle. These findings demonstrate a mouse model of laparotomy which recapitulated some features of post-operative skeletal muscle decline in older adults following surgery, and identified age-associated, laparotomy-induced molecular signatures in skeletal muscles. Future research can build upon this mouse model to study molecular mechanisms of late-life vulnerability to acute surgical stress and resiliency to counter surgery-induced physical decline.

Ubiquinol Supplementation Alters Exercise Induced Fatigue by Increasing Lipid Utilization in Mice

Ubiquinol (QH), a reduced form of coenzyme Q10, is a lipid antioxidant that is hydro-soluble and is commonly formulated in commercial supplements. Ubiquinol has been increasingly reported to exert antioxidant functions, in addition to its role in the cell energy-producing system of mitochondria and adenosine triphosphate (ATP) production. The aim of this study was to assess the potential beneficial effects of QH on anti-fatigue and ergogenic functions following physiological challenge. Forty 8-week-old male Institute of Cancer Research (ICR) mice were divided into four groups (n = 10 for each group): Group 1 (vehicle control or oil only); Group 2 (1X QH dose or 102.5 mg/kg); Group 3 (2X QH dose or 205 mg/kg); Group 4 (6X QH dose or 615 mg/kg). Anti-fatigue activity and exercise performance were studied using the forelimb grip strength experiment and exhaustive weight-loaded swimming time, and levels of serum lactate, ammonia, glucose, BUN (blood urea nitrogen), creatine kinase (CK), and free fatty acids (FFA) after an acute exercise challenge. The forelimb grip strength and exhaustive weight-loaded swimming time of the QH-6X group were significantly higher than those of the other groups. QH supplementation dose-dependently reduced serum lactate, ammonia, and CK levels and increased the FFA concentration after acute exercise. In addition, QH increased the liver and muscle glycogen content, an important energy source during exercise. Therefore, the results suggest that QH formulation is a safe dietary supplement for amelioration of fatigue and for promoting exercise performance.

Antifatigue Activity and Exercise Performance of Phenolic-Rich Extracts from Calendula officinalis, Ribes nigrum, and Vaccinium myrtillus

Calendula officinalis, Ribes nigrum, and Vaccinium myrtillus (CRV) possess a high phenolic compound content with excellent antioxidant activity. Dietary antioxidants can reduce exercise-induced oxidative stress. Consumption of large amounts of phenolic compounds is positively correlated with reduction in exercise-induced muscle damage. Research for natural products to improve exercise capacity, relieve fatigue, and accelerate fatigue alleviation is ongoing. Here, CRV containing a large total phenolic content (13.4 mg/g of CRV) demonstrated antioxidant activity. Ultra-performance liquid chromatography quantification revealed 1.95 ± 0.02 mg of salidroside in 1 g of CRV. In the current study, CRV were administered to mice for five weeks, and the antifatigue effect of CRV was evaluated using the forelimb grip strength test; weight-loaded swimming test; and measurement of fatigue-related biochemical indicators, such as blood lactate, ammonia, glucose, blood urea nitrogen (BUN), and creatine kinase (CK) activity; and muscle and liver glycogen content. The results indicated that in CRV-treated mice, the forelimb grip strength significantly increased; weight-loaded swimming time prolonged; their lactate, ammonia, BUN, and CK activity decreased, and muscle and liver glucose and glycogen content increased compared with the vehicle group. Thus, CRV have antifatigue activity and can increase exercise tolerance.

A New Model of Diarrhea with Spleen-Kidney Yang Deficiency Syndrome

Objective. The aim of this study was to examine a new method to create a rat model of diarrhea with spleen-kidney yang deficiency syndrome. Methods. A senna leaf (Folium sennae) decoction was made in 3 concentrations of 1.0, 0.5, and 0.25 g/mL. Rats were randomly divided into 4 groups: the control (C)-, high (H)-, middle (M)-, and low (L)- dose groups. The groups received saline, 1.0, 0.5, or 0.25 g/mL senna leaf decoction, respectively, for 4 weeks. Body weight monitoring, food consumption, water intake, defecation frequency, stool Bristol score, weight-loaded forced swimming test, forelimb grip strength test, D-xylose absorption test, serum cortisone, adrenocorticotropic hormone (ACTH), 24 h urine 17-hydroxycorticosteroid (17-OHCS), and histopathological detection were conducted to assess the success of the senna leaf decoction-induced model. Results. This study showed that the senna leaf decoction could induce diarrhea and dose-dependently slow body weight growth, reduce food consumption, and increase water intake, stool Bristol score, and defecation frequency. Statistical differences were found between groups H and M in rectal temperature, weight-loaded forced swimming time, forelimb grip strength, and serum cortisone. The D-xylose absorption test also showed dysfunction of intestinal absorption in groups H and M. The serum cortisone and 24 h urine 17-OHCS were significantly reduced in group H. Conclusions. Gastric gavage of 10 mL/kg of body weight of a high concentration of a senna leaf decoction (1.0 g/mL) for 4 weeks was used to create a rat model of diarrhea with spleen-kidney yang deficiency syndrome.

Altered expression of genes regulating skeletal muscle mass in the portacaval anastamosis rat

We examined the temporal relationship between portacaval anastamosis (PCA), weight gain, changes in skeletal muscle mass and molecular markers of protein synthesis, protein breakdown, and satellite cell proliferation and differentiation. Male Sprague-Dawley rats with end to side PCA ( n = 24) were compared with sham-operated pair-fed rats ( n = 24). Whole body weight, lean body mass, and forelimb grip strength were determined at weekly intervals. The skeletal muscle expression of the ubiquitin proteasome system, myostatin, its receptor (the activin 2B receptor) and its signal, cyclin-dependant kinase inhibitor (CDKI) p21, insulin-like growth factor (IGF)-I and its receptor (IGF-I receptor-α), and markers of satellite cell proliferation and differentiation were quantified. PCA rats did not gain body weight and had lower lean body mass, forelimb grip strength, and gastrocnemius muscle weight. The skeletal muscle expression of the mRNA of ubiquitin proteasome components was higher in PCA rats in the first 2 wk followed by a lower expression in the subsequent 2 wk ( P < 0.01). The mRNA and protein of myostatin, activin 2B receptor, and CDKI p21 were higher, whereas IGF-I and its receptor as well as markers of satellite cell function (proliferating nuclear cell antigen, myoD, myf5, and myogenin) were lower at weeks 3 and 4 following PCA ( P < 0.05). We conclude that PCA resulted in uninhibited proteolysis in the initial 2 wk. This was followed by an adaptive response in the later 2 wk consisting of an increased expression of myostatin that may have contributed to reduced muscle protein synthesis, impaired satellite cell function, and lower skeletal muscle mass.