Report for the Eighth Asian National Control Laboratory Network meeting in 2023: Self-sufficiency strategy of plasma-derived medicinal products and regulatory harmonisation.

The Eighth Asian National Control Laboratory (NCL) Network meeting, entitled "Biological Products Quality Control and Self-Sufficiency Strategy focusing on plasma-derived medicinal products (PDMPs)" was held in Seoul on 31 August 2023. The participants were NCL experts from Indonesia, Japan, Malaysia, the Philippines, Vietnam, and the Republic of Korea. Special lectures included the PDMPs self-sufficiency strategies of the World Health Organization (WHO) and Indonesian Food and Drug Authority, and a case study on Global Benchmarking Tool (GBT) assessment for vaccines by the Korea Ministry of Food and Drug Safety. The NCL delegates shared their current experiences with national lot releases and biological standardisation. The meeting contributed to a mutual understanding of the progress of the PDMPs self-sufficiency among Asian countries, the WHO's support strategies, and the NCL's plan for the preparation of the WHO GBT assessment. In the panel discussion, all participants agreed that building capacity in blood safety in the Asian region and harmonisation of relevant international regulatory requirements will support appropriate emergency preparedness, particularly source materials in the region, and will build the foundation for resolving the PDMPs supply insecurity that has worsened after the COVID-19 pandemic in some countries.

Combined effects of sleep and objectively-measured daily physical activity on arterial stiffness in middle-aged and older adults.

Although sleep quality and physical activity (PA) may influence on arterial stiffness, the combined effects of these two factors on arterial stiffness remain unknown. A total of 103 healthy middle-aged and older men and women (aged 50-83 years) with no history of cardiovascular disease and depression were included in this study. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV), brachial-ankle PWV (baPWV), and femoral-ankle PWV (faPWV). Poor sleepers were defined as those with a Pittsburgh Sleep Quality Index score of >5.5. Using an accelerometer for seven consecutive days, low levels of PA were defined as low moderate-to-vigorous-intensity PA (MVPA) <19.0 min/day and low step counts <7100 steps/day, respectively. Poor sleepers with low PA levels, as determined by MVPA and daily steps, showed higher cfPWV, but not faPWV or baPWV, in middle-aged and older adults. Furthermore, in the analysis of covariance (ANCOVA) analyses adjusted for age, obesity, dyslipidemia, and sedentary behavior, the cfPWV result remained significant. Our study revealed that the coexistence of poor sleep quality and decreased PA (low MVPA or daily steps) might increase central arterial stiffness in middle-aged and older adults. Therefore, adequate sleep (good and sufficient sleep quality) and regular PA, especially at appropriate levels of MVPA (i.e., at least of 7100 steps/day), should be encouraged to decrease central arterial stiffness in middle-aged and older adults.

Ashwagandha Ethanol Extract Attenuates Sarcopenia-Related Muscle Atrophy in Aged Mice.

The investigation focused on the impact of Withania somnifera (ashwagandha) extract (WSE) on age-related mechanisms affecting skeletal muscle sarcopenia-related muscle atrophy in aged mice. Beyond evaluating muscular aspects, the study explored chronic low-grade inflammation, muscle regeneration, and mitochondrial biogenesis. WSE administration, in comparison to the control group, demonstrated no significant differences in body weight, diet, or water intake, affirming its safety profile. Notably, WSE exhibited a propensity to reduce epidermal and abdominal fat while significantly increasing muscle mass at a dosage of 200 mg/kg. The muscle-to-fat ratio, adjusted for body weight, increased across all treatment groups. WSE administration led to a reduction in the pro-inflammatory cytokines TNF-α and IL-1ß, mitigating inflammation-associated muscle atrophy. In a 12-month-old mouse model equivalent to a 50-year-old human, WSE effectively preserved muscle strength, stabilized grip strength, and increased muscle tissue weight. Positive effects were observed in running performance and endurance. Mechanistically, WSE balanced muscle protein synthesis/degradation, promoted fiber differentiation, and enhanced mitochondrial biogenesis through the IGF-1/Akt/mTOR pathway. This study provides compelling evidence for the anti-sarcopenic effects of WSE, positioning it as a promising candidate for preventing sarcopenia pending further clinical validation.

The role of continuous glucose monitoring in physical activity and nutrition management: perspectives on present and possible uses.

PURPOSE: Continuous glucose monitoring (CGM) is on the rise as the prevalence of obesity and diabetes increases. This review aimed to explore the use of CGM and its potential novel applications in physical activity and nutrition management. METHODS: We searched PubMed, Web of Science, and Wiley Online Library databases using the keywords 'continuous glucose monitor,' 'nutrition,' 'physical activity,' and 'numerical modeling.' RESULTS: Continuous blood glucose measurement is useful for individuals with obesity and diabetes. Long-term blood glucose data allow for personalized planning of nutritional composition, meal timing, and physical activity type and intensity, as well as help prevent hypoglycemia and hyperglycemia. Thus, understanding the limitations of CGM is important for its effective use. CONCLUSION: CGM systems are being increasingly used to monitor and identify appropriate blood glucose controlling interventions. Blood glucose level is influenced by various factors such as nutrient composition, meal timing, physical activity, circadian rhythm, and cortisol levels. Numerical modeling can be used to analyze the complex relationship between stress, sleep, nutrition, and physical activity, which affect blood glucose levels. In future, blood glucose, sleep, and stress data will be integrated to predict appropriate lifestyle levels for blood glucose management. This integrated approach improves glucose control and overall wellbeing, potentially reducing societal costs.

Effect of curcumin supplementation on inflammatory status and muscle damage in competitive female soccer players: a placebo-controlled, singleblind, nonrandomized, crossover pilot study.

PURPOSE: Curcumin, a major component of turmeric, has anti-inflammatory and antioxidative properties, which are associated with protective effects against muscle damage. This study examined the effects of dietary curcumin on inflammation and muscle damage in female competitive soccer players. METHODS: A single-blinded, placebo-controlled, nonrandomized, crossover pilot study was conducted. Six competitive female soccer players (20.0 ± 2.0 yearsold) who participated in a 2-week preseason training program were assigned to two conditions: placebo and curcumin. The participants ingested a placebo or curcumin dosage (270 mg/day) during 2 weeks of preseason training, with 1 week of washout. Fasting blood samples were collected under resting conditions before (day 0) and after (day 15) the training period to examine changes in the concentration of interleukin 6 (IL-6), an inflammatory marker, and indices reflective of muscle damage. RESULTS: Curcumin decreased the concentration of IL-6 released (mean decrease, -30.2 ± 28.1%), whereas no decrease was observed in the placebo condition (13.4 ± 17.4%). Changes in plasma IL-6 concentrations were significantly greater in the curcumin condition than in the placebo condition (p < 0.05). However, curcumin supplementation had no significant effects on muscle damage indices. CONCLUSION: The present study shows that curcumin supplementation could attenuate inflammation, as indicated by IL-6 concentrations, in competitive female soccer players during the training period.

Attention-Based Bi-Prediction Network for Versatile Video Coding (VVC) over 5G Network.

As the demands of various network-dependent services such as Internet of things (IoT) applications, autonomous driving, and augmented and virtual reality (AR/VR) increase, the fifthgeneration (5G) network is expected to become a key communication technology. The latest video coding standard, versatile video coding (VVC), can contribute to providing high-quality services by achieving superior compression performance. In video coding, inter bi-prediction serves to improve the coding efficiency significantly by producing a precise fused prediction block. Although block-wise methods, such as bi-prediction with CU-level weight (BCW), are applied in VVC, it is still difficult for the linear fusion-based strategy to represent diverse pixel variations inside a block. In addition, a pixel-wise method called bi-directional optical flow (BDOF) has been proposed to refine bi-prediction block. However, the non-linear optical flow equation in BDOF mode is applied under assumptions, so this method is still unable to accurately compensate various kinds of bi-prediction blocks. In this paper, we propose an attention-based bi-prediction network (ABPN) to substitute for the whole existing bi-prediction methods. The proposed ABPN is designed to learn efficient representations of the fused features by utilizing an attention mechanism. Furthermore, the knowledge distillation (KD)- based approach is employed to compress the size of the proposed network while keeping comparable output as the large model. The proposed ABPN is integrated into the VTM-11.0 NNVC-1.0 standard reference software. When compared with VTM anchor, it is verified that the BD-rate reduction of the lightweighted ABPN can be up to 5.89% and 4.91% on Y component under random access (RA) and low delay B (LDB), respectively.

G-quadruplexes formed by Varicella-Zoster virus reiteration sequences suppress expression of glycoprotein C and regulate viral cell-to-cell spread.

G-quadruplex (G4) formed by repetitive guanosine-rich sequences plays important roles in diverse cellular processes; however, its roles in viral infection are not fully understood. In this study, we investigated the genome-wide distribution of G4-forming sequences (G4 motifs) in Varicella-Zoster virus (VZV) and found that G4 motifs are enriched in the internal repeat short and the terminal repeat short regions flanking the unique short region and also in some reiteration (R) sequence regions. A high density of G4 motifs in the R2 region was found on the template strand of ORF14, which encodes glycoprotein C (gC), a virulent factor for viral growth in skin. Analyses such as circular dichroism spectroscopy, thermal difference spectra, and native polyacrylamide gel electrophoresis with oligodeoxynucleotides demonstrated that several G4 motifs in ORF14 form stable G4 structures. In transfection assays, gC expression from the G4-disrupted ORF14 gene was increased at the transcriptional level and became more resistant to suppression by G4-ligand treatment. The recombinant virus containing the G4-disrupted ORF14 gene expressed a higher level of gC mRNA, while it showed a slightly reduced growth. This G4-disrupted ORF14 virus produced smaller plaques than the wild-type virus. Our results demonstrate that G4 formation via reiteration sequences suppresses gC expression during VZV infection and regulates viral cell-to-cell spread.

Dynapenic-abdominal obesity as an independent risk factor for chronic kidney disease in postmenopausal women: a population-based cohort study.

OBJECTIVE: Low muscle strength and obesity lead to a higher risk of chronic kidney disease (CKD). Perimenopause is associated with a natural decline in muscle strength and an increase in visceral adiposity. Dynapenic obesity, which is the coexistence of low muscle strength and obesity, is expected to synergistically increase the prevalence of CKD in postmenopausal women. The aim of this study was to determine combined associations of dynapenia and obesity with CKD in postmenopausal women. METHODS: This study used data from the Korean National Health and Nutrition Examination Survey, 2016 to 2019. The study included 4,525 postmenopausal women aged 42 to 80 years that were classified into four groups based on waist circumference (≥85 cm) and hand grip strength (<18 kg): normal, dynapenic, obese, or dynapenic-obese. According to the Kidney Disease: Improving Global Outcomes, we defined CKD as an estimated glomerular filtration rate <60 mL/min per 1.73 m2. Complex sample logistic regression models were conducted to determine the relationships among coexistence of dynapenia, abdominal obesity, and the risk of CKD. RESULTS: Dynapenic-abdominal obese group displayed lower estimated glomerular filtration rate levels than other groups (P < 0.05 for all data). The prevalence rates of CKD were 15.5%, 7.8%, 6.2%, and 2.4% in the dynapenic-abdominal obese, dynapenic, abdominal obese, and normal groups, respectively (P < 0.001). Complex sample logistic regression analyses, after adjusting for age, height, health behaviors, and comorbidities, showed that the odds ratio for CKD with respect to dynapenic-abdominal obesity was 1.82 (95% confidence interval, 1.19-2.79) and to abdominal obesity was 1.54 (95% confidence interval, 1.07-2.22) than in the normal group. CONCLUSIONS: This study demonstrated that dynapenic-abdominal obesity, as determined by low handgrip strength and high waist circumference values, was associated with increased risk of CKD in postmenopausal women.

Sports activities at a young age decrease hypertension risk-The J-Fit+ study.

This study aimed to assess (1) blood pressure between young, current athletes, and non-athletes early in life; (2) hypertension prevalence between former athletes and the general population later in life; and (3) understand the mechanisms between exercise training and hypertension risks in the form of DNA methylation. Study 1: A total of 354 young male participants, including current athletes, underwent blood pressure assessment. Study 2: The prevalence of hypertension in 1269 male former athletes was compared with that in the Japanese general population. Current and former athletes were divided into three groups: endurance-, mixed-, and sprint/power-group. Study 3: We analyzed the effect of aerobic- or resistance-training on DNA methylation patterns using publicly available datasets to explore the possible underlying mechanisms. In young, current athletes, the mixed- and sprint/power-group exhibited higher systolic blood pressure, and all groups exhibited higher pulse pressure than non-athletes. In contrast, the prevalence of hypertension in former athletes was significantly lower in all groups than in the general population. Compared to endurance-group (reference), adjusted-hazard ratios for the incidence of hypertension among mixed- and sprint/power-group were 1.24 (0.87-1.84) and 1.50 (1.04-2.23), respectively. Moreover, aerobic- and resistance-training commonly modified over 3000 DNA methylation sites in skeletal muscle, and these were suggested to be associated with cardiovascular function-related pathways. These findings suggest that the high blood pressure induced by exercise training at a young age does not influence the development of future hypertension. Furthermore, previous exercise training experiences at a young age could decrease the risk of future hypertension.

Role of exercise in estrogen deficiency-induced sarcopenia.

A decline in estrogen levels during menopause is associated with the loss of muscle mass and function, and it can accelerate sarcopenia. However, with the growing number of postmenopausal women due to the increase in life expectancy, the effects of estrogen on skeletal muscle are not completely understood. This article reviews the relationship between estrogen deficiency and skeletal muscle, its potential mechanisms, including those involving mitochondria, and the effects of exercise on estrogen deficiency-induced skeletal muscle impairment. In particular, mitochondrial dysfunction induced by estrogen deficiency accelerates sarcopenia via mitochondrial dynamics, mitophagy, and mitochondrial-mediated apoptosis. It is well known that exercise training is essential for health, including for the improvement of sarcopenia. This review highlights the importance of exercise training (aerobic and resistance exercise) as a therapeutic intervention against estrogen deficiency-induced sarcopenia.

Body height determines carotid stiffness following resistance exercise in young Japanese men.

Height is inversely associated with an increase in arterial stiffness after habitual resistance exercise (RE). Considering that RE is performed during exercise prescriptions, the association between height and the acute effects of RE on arterial stiffness should be clarified. We investigated the effects of height on arterial stiffness following transient RE. Thirty-nine young Japanese men were studied under parallel experimental conditions [sham control (seated rest) and RE (5 sets of 10 repetitions at 75% of one-repetition maximum)], which were randomly ordered on two separate days. The subjects were divided into tertiles of height (each group, n = 13). The ß-stiffness index (index of arterial stiffness), assessed by carotid pulse pressure and distension, was measured in all subjects. A significant interaction between time, height, and RE was found for the ß-stiffness index (P = 0.01). RE significantly increased the ß-stiffness index in the lower-height group (P < 0.001), but not in the middle- and higher-height groups. Height was negatively associated with an increase in ß-stiffness index following RE, even after controlling the confounders, including exercise volume and changes in heart rate and carotid pulse pressure (P = 0.003). The mediation analysis demonstrated a mediating effect of carotid distension on the relationship between height and changes in the ß-stiffness index. These results suggest that short height individuals have increased arterial stiffness following RE due to decreased mechanical distension, rather than through the widening of pulsatile pressure.

Effects of nocturnal light exposure on circadian rhythm and energy metabolism in healthy adults: A randomized crossover trial.

Exposure to continuous light at night, including night-shift work or a nocturnal lifestyle, is emerging as a novel deleterious factor for weight gain and obesity. Here, we examined whether a single bout of bright light (BL) exposure at night affects energy metabolism via changes in circadian rhythm and nocturnal melatonin production. Ten healthy young men were randomized to a two-way crossover experimental design protocol: control (< 50 lux) and BL (approximately 10000 lux) conditions, with at least seven days of interval. The participants were exposed to each condition for 3 h (21:00-24:00) before sleep (0 lux, 00:00-07:00) in a room-type metabolic chamber. On each experimental night (21:00-07:00), energy expenditure, respiratory quotient (RQ), and substrate oxidation were measured to determine the energy metabolism. BL exposure prior to bedtime altered biological rhythms, disrupted the nocturnal decline in body temperature, and suppressed the melatonin level before sleeping, resulting in an increase in sleep latency. Indirect calorimetry data revealed that BL exposure significantly decreased the fat oxidation and increased the RQ, an indicator of the carbohydrate-to-fat oxidation ratio, throughout the whole period (light exposure and sleep). We revealed that acute BL exposure prior to bedtime exacerbated circadian rhythms and substrate oxidations, suggesting that chronic BL exposure at night may lead to obesity risk due to disturbances in circadian rhythms and macronutrient metabolism.

Stature is negatively associated with increased arterial stiffness after high-intensity bicep curls training in young Japanese men.

Reports have indicated that high-intensity resistance training (RT) increases or does not change arterial stiffness. Meanwhile, higher stature has been suggested to have a protective effect on cardiovascular disease and arterial stiffness. Stature could explain the disagreement in the reported effects of RT on arterial stiffness. This study was aimed at investigating whether stature is related to RT-induced change in arterial stiffness. Thirty-six young Japanese men were assigned to the control (n = 15) and training groups (n = 21). RT programme consisted of supervised bicep curls 3 days per week for 4 weeks (5 sets of 10 repetitions at 75% of 1-repetition maximum). Arterial compliance (AC) and ß-stiffness index (via combination of ultrasound and carotid pressure waveforms) were measured in all participants. To verify the effect of stature on RT-induced change in arterial stiffness, the training group was divided into tertiles of stature: lower, middle, and higher stature groups (each group, n = 7). RT significantly decreased AC and increased ß-stiffness index in only the lower stature group (both, P < 0.05). Moreover, stature was positively associated with decreased AC and negatively associated with increased ß-stiffness index, even after adjusting for confounders including changes in relative strength, pulse pressure, and arterial distension (P < 0.05). The present results suggest that short stature contributes to the increase in arterial stiffness induced by RT in young Japanese men. The present findings suggest that stature should be taken into consideration when designing/engaging in RT programme, due to potential implications for cardiovascular health. HighlightsParticipants were divided into 3 groups according to tertiles of statures, and arterial stiffness of lower stature group (range of stature: 161.0-169.8 cm) increased after resistance training in young Japanese men, but not middle and higher stature group.Stature was negatively associated with the changed arterial stiffness by resistance training.This study suggests that short stature contributes to the elevation in arterial stiffness elicited by resistance training.

Exercise Training Attenuates Ovariectomy-Induced Alterations in Skeletal Muscle Remodeling, Apoptotic Signaling, and Atrophy Signaling in Rat Skeletal Muscle.

PURPOSE: The effects of aerobic exercise training on soleus muscle morphology, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in ovariectomized rat skeletal muscle were investigated. METHODS: Female Sprague-Dawley rats were divided into control (CON), ovariectomy (OVX), and ovariectomy plus exercise (OVX+EX) groups. After ovarian excision, exercise training was performed using a rat treadmill at 20 m/min, 50 min/day, 5 days/week for 12 weeks. Protein levels of mitochondria-mediated apoptotic signaling and atrophy/hypertrophy signaling in the skeletal muscle (soleus) were examined through western immunoblot analysis. RESULTS: The number of myocytes and myocyte cross-sectional area (CSA) were increased and the extramyocyte space was decreased in the OVX group compared to those in the CON group. However, aerobic exercise training significantly increased myocyte CSA and decreased extramyocyte space in the OVX+EX group compared to those in the OVX group. The protein levels of proapoptotic signaling and muscle atrophy signaling were significantly increased, whereas the protein levels of muscle hypertrophy signaling were significantly decreased in the OVX group compared to that in the CON group. Aerobic exercise training significantly decreased the protein levels of proapoptotic signaling and increased the protein level of antiapoptotic protein in the OVX+EX group compared to that in the OVX group. Aerobic exercise training significantly increased the protein levels of hypertrophy signaling and decreased protein levels of atrophy signaling in the OVX+EX group compared to those in the OVX group. CONCLUSION: Treadmill exercise improved estrogen deficiency-induced impairment in skeletal muscle remodeling, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in skeletal muscle.

Residual-Based Graph Convolutional Network for Emotion Recognition in Conversation for Smart Internet of Things.

Recently, emotion recognition in conversation (ERC) has become more crucial in the development of diverse Internet of Things devices, especially closely connected with users. The majority of deep learning-based methods for ERC combine the multilayer, bidirectional, recurrent feature extractor and the attention module to extract sequential features. In addition to this, the latest model utilizes speaker information and the relationship between utterances through the graph network. However, before the input is fed into the bidirectional recurrent module, detailed intrautterance features should be obtained without variation of characteristics. In this article, we propose a residual-based graph convolution network (RGCN) and a new loss function. Our RGCN contains the residual network (ResNet)-based, intrautterance feature extractor and the GCN-based, interutterance feature extractor to fully exploit the intra-inter informative features. In the intrautterance feature extractor based on ResNet, the elaborate context feature for each independent utterance can be produced. Then, the condensed feature can be obtained through an additional GCN-based, interutterance feature extractor with the neighboring associated features for a conversation. The proposed loss function reflects the edge weight to improve effectiveness. Experimental results demonstrate that the proposed method achieves superior performance compared with state-of-the-art methods.

Moderate aerobic exercise training ameliorates impairment of mitochondrial function and dynamics in skeletal muscle of high-fat diet-induced obese mice.

The purpose of this study is to determine whether moderate aerobic exercise training improves high-fat diet-induced alterations in mitochondrial function and structure in the skeletal muscle. Male 4-week-old C57BL/6 mice were randomly divided into four groups: control (CON), control plus exercise (CON + EX), high-fat diet (HFD), and high-fat diet plus exercise (HFD + EX). After obesity was induced by 20 weeks of 60% HFD, treadmill exercise training was performed at 13-16 m/min, 40-50 min/day, and 6 days/week for 12 weeks. Mitochondrial structure, function, and dynamics, and mitophagy were analyzed in the skeletal muscle fibers from the red gastrocnemius. Exercise training increased mitochondrial number and area and reduced high-fat diet-induced obesity and hyperglycemia. In addition, exercise training attenuated mitochondrial dysfunction in the permeabilized myofibers, indicating that HFD-induced decrease of mitochondrial O2 respiration and Ca2+ retention capacity and increase of mitochondrial H2 O2 emission were attenuated in the HFD + EX group compared to the HFD group. Exercise also ameliorated HFD-induced imbalance of mitochondrial fusion and fission, demonstrating that HFD-induced decrease in fusion protein levels was elevated, and increase in fission protein levels was reduced in the HFD + EX groups compared with the HFD group. Moreover, dysregulation of mitophagy induced by HFD was mitigated in the HFD + EX group, indicating a decrease in PINK1 protein level. Our findings demonstrated that moderate aerobic exercise training mitigated obesity-induced insulin resistance by improving mitochondrial function, and reversed obesity-induced mitochondrial structural damage by improving mitochondrial dynamics and mitophagy, suggesting that moderate aerobic exercise training may play a therapeutic role in protecting the skeletal muscle against mitochondrial impairments and insulin resistance induced by obesity.

Different degree of intervention in 6-month weight-loss support and arterial stiffness: Secondary analysis of a randomized controlled trial.

BACKGROUND AND AIMS: Weight reduction by lifestyle modification (i.e., low-calorie diet and/or exercise) decreases arterial stiffness in overweight or obese individuals. We previously demonstrated that weight loss differs depending on the degree of intervention in weight-loss support in a randomized controlled trial (UMIN000001259). However, the effect of different degrees of intervention on arterial stiffness remains unclear. METHODS AND RESULTS: A total of 188 middle-aged men and women with overweight or obesity (51 ± 7 years, BMI: 29.0 ± 3.2 kg/m2) participated in the 6-month trial wherein they were assigned to a low (LI, n = 63), moderate (MI, n = 62), or high intensive intervention (HI, n = 63) group. Initially, one motivational lecture on weight loss was provided to all three groups, whereas educational materials (textbooks, notebooks, and a pedometer) were provided to groups MI and HI. Additionally, the HI group participated in a series of group-based sessions. Body weight and arterial stiffness assessed by brachial-ankle pulse wave velocity (baPWV) were measured at 0, 3, and 6 months. Six-month weight loss was greater in the order of HI, MI, and LI groups. The interventions reduced baPWV in all groups, and the reduction was not significantly different among the groups (114.3 ± 16.3, 82.6 ± 15.2, and 98.8 ± 90.4 cm/s, respectively). CONCLUSION: In overweight or obese individuals, different degrees of intervention in weight-loss support affect body weight; however, the extent to which arterial stiffness improves does not differ among support programs.

Exercise as a Therapeutic Strategy for Sarcopenia in Heart Failure: Insights into Underlying Mechanisms.

Sarcopenia, a syndrome commonly seen in elderly populations, is often characterized by a gradual loss of skeletal muscle, leading to the decline of muscle strength and physical performance. Growing evidence suggests that the prevalence of sarcopenia increases in patients with heart failure (HF), which is a dominant pathogenesis in the aging heart. HF causes diverse metabolic complications that may result in sarcopenia. Therefore, sarcopenia may act as a strong predictor of frailty, disability, and mortality associated with HF. Currently, standard treatments for slowing muscle loss in patients with HF are not available. Therefore, here, we review the pathophysiological mechanisms underlying sarcopenia in HF as well as current knowledge regarding the beneficial effects of exercise on sarcopenia in HF and related mechanisms, including hormonal changes, myostatin, oxidative stress, inflammation, apoptosis, autophagy, the ubiquitin-proteasome system, and insulin resistance.

Aging Promotes Mitochondria-Mediated Apoptosis in Rat Hearts.

Aging represents a major risk for developing cardiac disease, including heart failure. The gradual deterioration of cell quality control with aging leads to cell death, a phenomenon associated with mitochondrial dysfunction in the heart. Apoptosis is an important quality control process and a necessary phenomenon for maintaining homeostasis and normal function of the heart. However, the mechanism of mitochondria-mediated apoptosis in aged hearts remains poorly understood. Here, we used male Fischer 344 rats of various ages, representing very young (1 month), young (4 months), middle-aged (12 months), and old (20 months) rats, to determine whether mitochondria-mediated apoptotic signals and apoptosis in the left ventricle of the heart are altered notably with aging. As the rats aged, the extramyocyte space and myocyte cross-sectional area in their left ventricle muscle increased, while the number of myocytes decreased. Additionally, mitochondrion-mediated apoptotic signals and apoptosis increased remarkably during aging. Therefore, our results demonstrate that aging promotes remarkable morphological changes and increases the degree of mitochondrion-mediated apoptosis in the left ventricle of rat hearts.

Re-Setting the Circadian Clock Using Exercise against Sarcopenia.

Sarcopenia is defined as the involuntary loss of skeletal muscle mass and function with aging and is associated with several adverse health outcomes. Recently, the disruption of regular circadian rhythms, due to shift work or nocturnal lifestyle, is emerging as a novel deleterious factor for the development of sarcopenia. The underlying mechanisms responsible for circadian disruption-induced sarcopenia include molecular circadian clock and mitochondrial function associated with the regulation of circadian rhythms. Exercise is a potent modulator of skeletal muscle metabolism and is considered to be a crucial preventative and therapeutic intervention strategy for sarcopenia. Moreover, emerging evidence shows that exercise, acting as a zeitgeber (time cue) of the skeletal muscle clock, can be an efficacious tool for re-setting the clock in sarcopenia. In this review, we provide the evidence of the impact of circadian disruption on skeletal muscle loss resulting in sarcopenia. Furthermore, we highlight the importance of exercise timing (i.e., scheduled physical activity) as a novel therapeutic strategy to target circadian disruption in skeletal muscle.