Comparison of the serum creatinine- and cystatin-C-based indices as screening biomarkers for sarcopenia in community-dwelling older adults.

BACKGROUND: Several creatinine- and cystatin-C-based indices have been proposed as sarcopenia predictors. This study aimed to compare serum creatinine- and cystatin-C-based indices as screening biomarkers for sarcopenia in community-dwelling older adults. METHODS: A cross-sectional study was conducted on 945 participants aged between 70 and 84 years (men=47.5%; mean age=76.0 ± 3.9 years) from the Korean Frailty and Aging Cohort Study. The serum creatinine-to-cystatin-C ratio estimated glomerular filtration rate (eGFR) ratio (eGFRcystatin-C/eGFRcreatinine), sarcopenia index (serum creatinine × eGFRcreatinine), predicted skeletal muscle mass index (pSMI), and total body muscle mass index (TBMM) were compared. RESULTS: The prevalence of sarcopenia was 19.9% in men and 14.0% in women. The pSMI and TBMM showed higher correlations with appendicular lean mass and grip strength in men (pSMI: rs=0.356-0.701, p < 0.001; TBMM: rs=0.320-0.730, p < 0.001) and women (pSMI: rs=0.299-0.669, p < 0.001; TBMM: rs=0.256-0.658, p < 0.001) than the other indices. The area under the receiver operating characteristic curves (AUC) of the serum indices for predicting sarcopenia showed the highest accuracy for pSMI (men: AUC=0.77, p < 0.001; women: AUC=0.71, p < 0.001). After adjusting for potential confounders, pSMI was associated with the likelihood of sarcopenia in both men (odds ratio [OR]=0.170; 95% confidence interval [CI]=0.103-0.279) and women (OR=0.167; 95% CI=0.087-0.321). CONCLUSION: pSMI and TBMM accurately determined sarcopenia than the other indices. Furthermore, a higher pSMI was strongly associated with a decreased risk of sarcopenia compared to TBMM. These findings suggest pSMI as a potential biomarker for sarcopenia screening in community-dwelling older adults.

Development of multiple biomarker panels for prediction of sarcopenia in community-dwelling older adults.

BACKGROUND: It is required to consider multiple biomarkers simultaneously to predict sarcopenia and to understand its complex pathological mechanisms. This study aimed to develop multiple biomarker panels for predicting sarcopenia in older adults and to further examine its association with the incidence of sarcopenia. METHODS: A total of 1,021 older adults were selected from the Korean Frailty and Aging Cohort Study. Sarcopenia was defined by the Asian Working Group for Sarcopenia 2019 criteria. Among the 14 biomarker candidates at baseline, eight biomarkers that could optimally detect individuals with sarcopenia were selected to develop a multi-biomarker risk score (range from 0 to 10). The utility of developed multi-biomarker risk score in discriminating sarcopenia was investigated using receiver operating characteristic (ROC) analysis. RESULTS: The multi-biomarker risk score had an area under the ROC curve (AUC) of 0.71 with an optimal cut-off of 1.76 score, which was significantly higher than all single biomarkers with AUC of <0.7 (all, p<0.01). During the two-year follow-up, the incidence of sarcopenia was 11.1%. Continuous multi-biomarker risk score was positively associated with incidence of sarcopenia after adjusting confounders (odds ratio [OR]=1.63; 95% confidence interval [CI]=1.23-2.17). Participants with a high risk score had higher odds of sarcopenia than those with a low risk score (OR=1.82; 95% CI=1.04-3.19). CONCLUSIONS: Multi-biomarker risk score, which was a combination of eight biomarkers with different pathophysiologies, better discriminated the presence of sarcopenia than a single biomarker, and it could further predict the incidence of sarcopenia over two years in older adults.

Combinations of Sarcopenia Diagnostic Criteria by Asian Working Group of Sarcopenia (AWGS) 2019 Guideline and Incident Adverse Health Outcomes in Community-Dwelling Older Adults.

OBJECTIVES: This study aimed to investigate the association between combinations of sarcopenia criteria by the Asian Working Group of Sarcopenia (AWGS) 2019 guideline and incident adverse health outcomes. DESIGN: Longitudinal analyses of a cohort study. SETTING AND PARTICIPANTS: We conducted prospective 2-year follow-up analyses (N = 1959) among community-dwelling older adults enrolled in the nationwide Korean Frailty and Aging Cohort Study (KFACS). METHODS: From the KFACS, 1959 older adults (52.8% women; mean age = 75.9 ± 3.9 years) who underwent assessments for appendicular skeletal mass using dual-energy X-ray absorptiometry, handgrip strength, usual gait speed, 5-times sit-to-stand test, and Short Physical Performance Battery (SPPB) at baseline were included. Participants with each adverse health outcome [mobility disability, falls, and instrumental activities of daily living (IADL) disabilities] at baseline were excluded for each corresponding analysis. Multivariable logistic regression was performed to examine whether sarcopenia defined by different diagnostic criteria was associated with incident adverse health outcomes after 2 years. RESULTS: A total of 444 participants (22.7%) were diagnosed with sarcopenia as defined by AWGS 2019. In the multivariable analysis, sarcopenia defined as both low muscle mass and low physical performance increased the risk of mobility disability (OR 2.14, 95% CI 1.35-3.38) and falls (1.74, 95% CI 1.21-2.49). Only the criterion defined as both low muscle mass and physical performance using the SPPB increased the risk of falls with fracture (2.53, 95% CI 1.01-6.35) and IADL disabilities (2.77, 95% CI 1.21-6.33). However, sarcopenia defined as both low muscle mass and low hand grip strength showed no associations with the incidence of any of the adverse health outcomes. CONCLUSIONS AND IMPLICATIONS: Our study suggests that the predictive value of adverse health outcomes for community-dwelling older adults is better when diagnosed with sarcopenia based on low muscle mass and physical performance. Furthermore, using the SPPB as a diagnostic tool for low physical performance may improve the predictive validity for falls with fracture and IADL disability. Our findings may be helpful for the early detection of individuals with sarcopenia who have a higher risk of adverse health outcomes.

Longitudinal association between eating alone and deterioration in frailty status: The Korean Frailty and Aging Cohort Study.

BACKGROUND: Among risk factors of developing frailty, dietary factor played an important role as a potentially modifiable risk factor. Eating alone is associated with malnutrition, depression, and social isolation, which are risk factors of frailty. We evaluated the longitudinal association between a change to eating alone and deterioration in frailty status in a cohort of community-dwelling elderly persons. METHODS: The study subjects were 2072 non-frail Korean elderly persons aged 70-84 years who were recruited for the Korean Frailty and Aging Cohort Study (KFACS). The subjects were divided into 4 groups based on changes in eating with others or alone between the baseline survey (2016-2017) and the follow-up survey (2018-2019): group I (ate with others consistently), group II (ate with others at baseline but ate alone at follow-up), group III (ate alone at baseline but ate with others at follow-up), group IV (ate alone consistently). We assessed physical frailty using the Cardiovascular Health Study (CHS) frailty phenotype. The association between changes in eating with others or alone and frailty progression was assessed by multiple logistic regression analysis after adjusting for covariates. RESULTS: The mean age of the study subjects was 76.2 (SD: 3.8) years old and 50.8 % were female. At follow-up, 364 new cases (34.5 %) of pre-frailty (n = 348) and frailty (n = 16) were identified among those who were robust at baseline (n = 1056), while 88 new cases (8.7 %) of frailty were identified among those who were pre-frail at baseline (n = 1016). Compared to group I, group II showed an increased risk of deterioration in frailty status after adjustments with multivariables including social isolation and malnutrition (adjusted odds ratio [aOR] = 1.61, 95 % confidence interval [CI]: 1.03-2.50). However, the association disappeared after further adjustment for depression. When we examined the longitudinal association between changes in eating with others or alone and changes in each frailty domain, group II showed an increased risk for the weight loss (aOR = 3.07, 95 % CI: 1.39-6.76) compared to group I. Group IV showed an increased risk for the weight loss (aOR = 2.39, 95 % CI: 0.95-6.00) and weakness (aOR = 2.07, 95 % CI: 1.16-3.68). CONCLUSIONS: A change from eating with others to eating alone was found to significantly increase the risk of deterioration in frailty status in elderly people, and the association seemed to be mediated by depression. These findings suggest that interventions to maintain eating partners and manage depression are needed to prevent frailty progression in elderly people.

Metabolomic profiles to explore biomarkers of severe sarcopenia in older men: A pilot study.

BACKGROUND: The pathophysiology of sarcopenia is complex and multifactorial; however, it has not yet been fully elucidated. Identifying metabolomic profiles may help clarify the mechanisms underlying sarcopenia. OBJECTIVE: This pilot study explored potential noninvasive biomarkers of severe sarcopenia through metabolomic analysis in community-dwelling older men. METHODS: Twenty older men (mean age: 81.9 ± 2.8 years) were selected from the Korean Frailty and Aging Cohort Study. Participants with severe sarcopenia (n = 10) were compared with non-sarcopenic, age- and body mass index-matched controls (n = 10). Severe sarcopenia was defined as low muscle mass, low muscle strength, and low physical performance using the Asian Working Group for Sarcopenia 2019 criteria. Non-targeted metabolomic profiling of plasma metabolites was performed using capillary electrophoresis time-of-flight mass spectrometry and absolute quantification was performed in target metabolites. RESULTS: Among 191 plasma metabolic peaks, the concentrations of 10 metabolites significantly differed between severe sarcopenia group and non-sarcopenic controls. The plasma concentrations of L-alanine, homocitrulline, N-acetylserine, gluconic acid, N-acetylalanine, proline, and sulfotyrosine were higher, while those of 4-methyl-2-oxovaleric acid, 3-methyl-2-oxovaleric acid, and tryptophan were lower in participants with severe sarcopenia than in non-sarcopenic controls (all, p < 0.05). Among the 53 metabolites quantified as target metabolites, L-alanine (area under the receiver operating characteristic curve [AUC] = 0.760; p = 0.049), gluconic acid (AUC = 0.800; p = 0.023), proline (AUC = 0.785; p = 0.031), and tryptophan (AUC = 0.800; p = 0.023) determined the presence of severe sarcopenia. CONCLUSIONS: Plasma metabolomic analysis demonstrated that L-alanine, gluconic acid, proline, and tryptophan may be potential biomarkers of severe sarcopenia. The identified metabolites can provide new insights into the underlying pathophysiology of severe sarcopenia and serve as the basis for preventive interventions.

Differences in Characteristics between Older Adults Meeting Criteria for Sarcopenia and Possible Sarcopenia: From Research to Primary Care.

Identification of possible sarcopenia, which is a simple assessment of sarcopenia, has been proposed for the earlier detection of sarcopenia in primary care settings; however, there are no studies comparing the differences in characteristics of older adults with possible sarcopenia or sarcopenia. This study aimed to compare the characteristics of "possible sarcopenia" in real-world primary care and "sarcopenia" in research settings. A total of 2129 older adults were enrolled from the Korean Frailty and Aging Cohort Study. Possible sarcopenia and sarcopenia were defined using Asian Working Group for Sarcopenia 2019; the possible sarcopenia for real-world primary care was defined by a combination of case findings using low calf circumference or the SARC-F questionnaire and 5-times chair stand test, without considering the measurement of handgrip strength. The prevalence of possible sarcopenia was higher in women than in men; however, that of sarcopenia was higher in men than in women (all, p < 0.001). Older men and women with possible sarcopenia had a lower education level, longer time taken for the Timed Up and Go test, more severe mobility limitation, lower scores on the EuroQol-5 dimension and 12-item short-form survey for physical health, and more cognitive dysfunction than those with sarcopenia did (all, p < 0.05). In conclusion, the participants with possible sarcopenia differed from those with sarcopenia in some characteristics. Identifying differences in characteristics may be helpful to screening and earlier diagnosis of sarcopenia in real-world primary care, as well as in research, which can lay the foundations for personalized lifestyle intervention in diet and exercise.

Corrigendum: Sex-Specific Differences in the Effect of Free Testosterone on Sarcopenia Components in Older Adults.

[This corrects the article DOI: 10.3389/fendo.2021.695614.].

Therapeutic Effects of Functional Electrical Stimulation on Physical Performance and Muscle Strength in Post-stroke Older Adults: A Review.

Stroke-related disabilities cause poor physical performance, especially among older adults, and can lead to sarcopenia. Functional electrical stimulation (FES) has been used to improve physical performance in individuals with neurological disorders and increase muscle mass and strength to counteract muscle atrophy. This review covers the principles, underlying mechanisms, and therapeutic effects of FES on physical performance and skeletal muscle function in post-stroke older adults. We found that FES restored weakened dorsiflexor and hip abductor strength during the swing and stance phases of gait, respectively, to help support weight-bearing and upright posture and facilitate static and dynamic balance in this population. FES may also be effective in improving muscle mass and strength to prevent muscle atrophy. However, previous studies on this topic in post-stroke older adults are scarce, and further studies are needed to confirm this supposition.

Sex-Specific Differences in the Effect of Free Testosterone on Sarcopenia Components in Older Adults.

Objective: The association of free testosterone (FT) with sarcopenia and its components is well known in men but incompletely understood in women. We examined the association of baseline FT with the prevalence and incidence of sarcopenia and its components in community-dwelling older adults. Design: Cross-sectional and longitudinal analysis from the prospective population-based Korean Frailty and Aging Cohort Study. Methods: A total of 1,879 community-dwelling older adults aged 70-84 years were enrolled for cross-sectional analysis and 1,583 subjects who participated in the 2-year follow-up survey were included for longitudinal analysis. Baseline FT levels was measured by radioimmunoassay. Skeletal muscle mass, handgrip strength, and physical performance tests were measured at baseline and after 2-year follow-up. Sarcopenia was defined by the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS). Results: Continuous FT levels was positively associated with the prevalence of sarcopenia in men (odds ratio [OR]=0.95; 95% confidence interval [CI]=0.89-1.00)] and women (OR=0.64, 95% CI=0.42-0.99) after adjusting for multiple confounders. In prospective analysis, low FT levels was associated with a decrease in handgrip strength in women (ß=-0.61; p=0.010) and a reduction in Timed "Up and Go" (TUG) test (ß=0.53; p=0.008) in men after 2 years. No significant correlations were found between FT levels and the incidence of sarcopenia. Conclusions: Low levels of FT may be a significant determinant of decreases in muscle strength in women and declines in physical performance in men after 2 years. Low FT do not predict loss of muscle mass in both men and women.

Association between plasma procollagen type III N-terminal peptide (P3NP) levels and physical performance in elderly men: The Korean Frailty and Aging Cohort Study (KFACS).

BACKGROUND: Physical performance decline associated with aging is clinically important in the development of disability in the older population. More recently, procollagen type III N-terminal peptide (P3NP) and synaptosomal-associated protein of 25 kDa (SNAP25) have been suggested as potential biomarkers for physical performance decline. OBJECTIVE: The objective of this pilot study was to examine plasma P3NP and SNAP25 levels in relation to muscle mass, strength, and performance status, and to investigate the association of plasma P3NP and SNAP25 levels with sarcopenia components. METHODS: Seventy-nine community-dwelling elderly men (mean age: 78.1 ± 3.5 years) were randomly selected and matched by age from the Korean Frailty and Aging Cohort Study. The sample was classified into the "normal," "low muscle mass only," "sarcopenia," and "low physical performance only" groups according to the criteria of the Asian Working Group for Sarcopenia 2019. Estimates and 95% confidence intervals (CIs) of log P3NP and log SNAP25 levels by muscle mass, strength, and performance status were obtained using a generalized linear model. Pearson correlations and multiple linear regression analyses were used to assess the association of log P3NP and log SNAP25 levels with appendicular skeletal muscle mass (ASM) index, handgrip strength, and physical performance. RESULTS: Log P3NP levels tended to be associated with low physical performance compared with the normal group (estimate = 0.54; 95% CI = -0.05, 1.14; p = 0.072). Log P3NP levels were inversely associated with physical performance (short physical performance battery and five-times sit-to-stand test) after adjusting for potential confounders (all p < 0.05) and tended to have an inverse association with gait speed (p = 0.078). Log P3NP levels tended to have a positive correlation with the ASM index (r2 = 0.042; p = 0.070), but not with handgrip strength (r2 = 0.0009; p = 0.795). However, no significant association between plasma SNAP25 levels and physical performance was observed. CONCLUSION: Plasma P3NP levels might be a potential biomarker for decreased physical performance in elderly men. Further studies with larger sample sizes are needed to confirm our findings.

The Effects of Exercise and Restriction of Sugar-Sweetened Beverages on Muscle Function and Autophagy Regulation in High-Fat High-Sucrose-Fed Obesity Mice.

BACKGROUND: Autophagy maintains muscle mass and healthy skeletal muscles. Several recent studies have associated sugar-sweetened beverage (SSB) consumption with diseases. We investigated whether muscle dysfunction due to obesity could be restored by SSB restriction (SR) alone or in combination with exercise (EX) training. METHODS: Obese mice were subjected to SR combined with treadmill EX. Intraperitoneal glucose tolerance test, grip strength test, hanging time test, and body composition analysis were performed. Triglyceride (TG) and total cholesterol (TC) serum concentrations and TG concentrations in quadriceps muscles were analyzed. Western blot and reverse transcription-quantitative polymerase chain reaction helped analyze autophagy-related protein and mRNA expression, respectively. RESULTS: SR alone had no significant effect on fasting blood glucose levels, glucose tolerance, and muscle function. However, it had effect on serum TC, serum TG, and BCL2 interacting protein 3 expression. SR+EX improved glucose tolerance and muscle function and increased serum TC utilization than SR alone. SR+EX reduced P62 levels, increased glucose transporter type 4 and peroxisome proliferator-activated receptor γ coactivator-1α protein expression, and improved grip strength relative to the high-fat and high-sucrose liquid (HFHS) group, and this was not observed in the HFHS+EX group. CONCLUSION: SR induced mitophagy-related protein expression in quadriceps, without affecting muscle function. And, the combination of SR and EX activated mitophagy-related proteins and improved muscle function.

Effects of Exercise and a High-Fat, High-Sucrose Restriction Diet on Metabolic Indicators, Nr4a3, and Mitochondria-Associated Protein Expression in the Gastrocnemius Muscles of Mice with Diet-Induced Obesity.

BACKGROUND: Exercise and high fat, high sucrose restriction diets are well known treatments for obesity. The aim of this study was to measure the effects of those lifestyle interventions on molecular transducers of exercise, such as Nr4a3, mitochondria-associated proteins, and muscle function. METHODS: We conducted 8 weeks of treadmill exercise and sucrose or fat restriction diets in obese mice. The mice were divided into eight groups: the normal diet (CON) group, normal diet with exercise (CONEX) group, high fat, high sucrose diet (HFHS) group, HFHS with exercise (HFHSEX) group, sucrose restriction (SR) group, SR with exercise (SREX) group, high fat, high sucrose restriction (ND) group, and ND with exercise (NDEX) group. RESULTS: The 8 weeks of exercise reduced body weight, improved lipid profiles (total cholesterol, triglycerides), and increased hanging time. The combination of exercise and a fat and sucrose restriction diet improved glucose tolerance and increased grip strength. The 8 weeks of intervention did not significantly affect the Nr4a3 protein level. The sucrose and fat restriction diet increased the phosphorylated protein kinase B (pAkt)/Akt ratio, and its level was lower in the HFHS group. Exercise increased the protein expression level of PGC-1α in obese conditions. Moreover, SR led reduced the phosphorylated AMP-activated protein kinase (pAMPK)/AMPK ratio and PGC-1α to the control level. CONCLUSION: The 8 weeks of exercise or a sucrose and fat restriction diet improved metabolic indicators and muscle function. SR reduced pAMPK/AMPK and PGC-1α to the control level. Nr4a3 protein expression was not significantly changed by either exercise or a fat and sucrose restriction diet.

Effects of exercise-induced beta-hydroxybutyrate on muscle function and cognitive function.

Recent studies have shown that exercise improves skeletal muscle and cognitive function by stimulating the secretion of numerous molecules. In particular, previous studies have suggested that exercise-induced beta-hydroxybutyrate (BHB) release might improve skeletal muscle and cognitive function, but to date these studies have been limited to cell and animal models. Therefore, we aimed to determine how an exercise-induced increase in BHB affects skeletal muscle and cognitive function at a cellular level, in an animal model, and in humans. The effects of BHB on skeletal muscle and cognitive function were determined by treating C2C12 and C6 cell lines with BHB, and by measuring the skeletal muscle and serum BHB concentrations in aged mice after endurance or resistance exercise. In addition, serum BHB concentration was measured before and after high-speed band exercise in elderly people, and its relationships with muscle and cognitive function were analyzed. We found that BHB increased cell viability and brain-derived neurotrophic factor expression level in C6 cells, and endurance exercise, but not resistance exercise, increased the muscle BHB concentration in aged mice. Furthermore, the BHB concentration was positively related to skeletal muscle and cognitive function. Exercise did not increase the serum BHB concentration in the elderly people and BHB did not correlate with cognitive function, but after excluding the five people with the highest preexisting serum concentrations of BHB, the BHB concentrations of the remaining participants were increased by exercise, and the concentration showed a tendency toward a positive correlation with cognitive function. Thus, the BHB released by skeletal muscle following endurance exercise may improve muscle and cognitive function in animals and humans.

Effects of treadmill exercise on the regulation of tight junction proteins in aged mice.

Tight junction protein is representative regulator of gut permeability. Also, it has been noted for controlling inflammatory responses through tight junction. Therefore, in this study, we examined that whether tight junction protein is changed in aged mice, and to further, confirmed the effect of treadmill exercise on the tight junction protein. In in vitro study, doxorubicin that induces cell senescence was treated to Caco2 cells (colon cell) to mimic aging effect. After that, 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR), exercise mimic chemical that stimulates AMPK level, was also administered to Caco2 cells. In animal study, 2 months and 21 months C57BL/6 J mouse were treated with treadmill exercise for 4 weeks (YE = 5, OE = 5). Then, the tight junction protein expression level was examined by western blot. Also, serum lipopolysaccharide (LPS) and zonulin level were analyzed to identify gut permeability. In vitro studies showed that doxorubicin downregulates tight junction protein expression levels in Caco2 cell, and also AICAR treatment upregulates tight junction protein expression levels. In animal study, 4 weeks treadmill exercise upregulated claudin-1 (p < 0.05) and occludin (p < 0.01) protein expression level in 21 months old mice. Also, zonula occluden-1 (ZO-1) protein expression level was not significant difference among all mice group. In addition, old mice group had higher level of serum LPS compared to young mice group, but the level was downregulated in both 2 months and 21 months mice group after four weeks of treadmill exercise. Zonulin, which is known as degrading tight junction protein, is not significantly changed by both age and exercise. This study compared that tight junction protein expression level in old mice compared to its level in young mice, and also clarified that the effect of treadmill exercise on tight junction protein in both young and old mice.

Lactate consumption mediates repeated high-intensity interval exercise-enhanced executive function in adult males.

PURPOSE: Lactate is a principal energy substrate for the brain during exercise. A single bout of high-intensity interval exercise (HIIE) can increase the blood lactate level, brain lactate uptake, and executive function (EF). However, repeated HIIE can attenuate exercise-induced increases in lactate level and EF. The lactate levels in the brain and blood are reported to be correlated with exercise-enhanced EF. However, research is yet to explain the cause-and-effect relationship between lactate and EF. This study examined whether lactate consumption improves the attenuated exerciseenhanced EF caused by repeated HIIE. METHODS: Eleven healthy men performed two sets of HIIE, and after each set, 30 min were given for rest and examination. In the 2nd set, the subjects consumed experimental beverages containing (n = 6) and not containing (n = 5) lactate. Blood, cardiovascular, and psychological variables were measured, and EF was evaluated by the computerized color-word Stroop test. RESULTS: The lactate group had a higher EF (P < 0.05) and tended to have a higher blood lactate level (P = 0.082) than the control group in the 2nd set of HIIE. Moreover, blood lactate concentration was correlated with the interference score (i.e., reverse score of EF) (r = -0.394; P < 0.05). CONCLUSION: Our results suggest that the attenuated exercise-enhanced EF after repeated HIIE can be improved through lactate consumption. However, the role of lactate needs to be elucidated in future studies, as it can be used for improving athletes' performance and also in cognitive decline-related clinical studies.

Effect of a Single Bout of Exercise on Autophagy Regulation in Skeletal Muscle of High-Fat High-Sucrose Diet-Fed Mice.

BACKGROUND: Autophagy maintains metabolic homeostasis of muscles, and its impairment may cause muscle dysfunction. Exercise can improve muscle dysfunction induced by long-term high-fat diet. This study aimed to explore the association of autophagy with impaired muscle dysfunction in obese conditions and investigate its relationship with exercise-induced muscle function improvement. METHODS: Male C57BL/6 mice (n=24) were randomly assigned to four groups: low-fat diet+plain water feeding sedentary (CON) group, low-fat diet+plain water feeding exercise (CON+EX) group, high-fat high-sucrose (HFHS) diet-fed sedentary group, and HFHS diet-fed exercise (HFHS+EX) group, and subjected to a single bout of exhaustive exercise. RESULTS: HFHS diet resulted in shorter hanging time, reduced grip force, and lower exhaustion time and distance, and decreased lean mass per body weight. Moreover, in the soleus, which is chosen as a representative red (oxidative) muscle, LC3II/LC3I ratio, P62, and Bnip3 levels were altered following the HFHS diet, and were negatively correlated with muscle performance parameters; exercise significantly decreased the LC3II/LC3 ratio while P62 increased with HFHS diet. Autophagy-related protein changes were not found in the white (glycolytic) gastrocnemius. CONCLUSION: The study revealed that 20-week HFHS diet causes a significant increase in body weight and fat mass, along with a decrease in muscle function. Autophagy-related LC3 and P62 protein expression was negatively correlated with muscle function, and they were reduced when a single bout of exercise stimulated the soleus of obese mice. However, no change of autophagy-related proteins was seen in the gastrocnemius.

Potential role of exercise-induced glucose-6-phosphate isomerase in skeletal muscle function.

PURPOSE: Recent studies have shown that glucose-6-phosphate isomerase (GPI)-which is a glycolysis interconversion enzyme-reduces oxidative stress. However, these studies are limited to tumors such as fibrosarcoma, and there are no studies that have examined the effects of exercise on GPI expression in mice skeletal muscle. Furthermore, GPI acts in an autocrine manner thorough its receptor, autocrine motility factor receptor (AMFR); therefore, we investigated expression level changes of secreted GPI from skeletal muscle in in vitro study to examine the potential role of GPI on skeletal muscle. METHODS: First, we performed an in vitro study, to identify the condition that upregulates GPI levels in skeletal muscle cells; we treated C2C12 muscle cells with an exercise-mimicking chemical, AICAR. AICAR treatment upregulated GPI expression level in C2C12 cell and its secretomes. To confirm the direct effect of GPI on skeletal muscle cells, we treated C2C12 cells with GPI recombinant protein. RESULTS: We found that GPI improved the viability of C2C12 cells. In the in vivo study, the exercise-treated mice group showed upregulated GPI expression in skeletal muscle. Based on the in vitro study results, we speculated that expression level of GPI in skeletal muscle might be associated with muscle function. We analyzed the association between GPI expression level and the grip strength of the all mice group. The mice group's grip strengths were upregulated after 2 weeks of treadmill exercise, and GPI expression level positively correlated with the grip strength. CONCLUSION: These results suggested that the exercise-induced GPI expression in skeletal muscle might have a positive effect on skeletal muscle function.

Exercise, the Gut Microbiome, and Frailty.

The gut microbiome is deeply associated with both skeletal muscle and brain function. In particular, gut microbiome dysbiosis may accelerate age-related diseases by affecting these systems. Although there is increasing evidence of the correlations between the gut microbiome and skeletal muscle and brain, it remains unclear whether changes in the gut microbiome due to exercise training can lead to healthy aging. This review covers the current status of gut microbiome-related research and future directions related to aging (e.g., physical frailty and cognitive dysfunction) as well as the effect of exercise training on both. We reviewed relevant literature including original articles and reviews identified from searches of the PubMed, Google Scholar, SCOPUS, EBSCOHost, ScienceDirect, Cochrane Library, and EMBASE databases using the following terms: 'gut microbiome', 'exercise', 'physical frailty', and 'cognitive dysfunction'. We identified a strong positive correlation between cognitive dysfunction or physical frailty and the gut microbiome. Furthermore, exercise had a significant effect on the composition of the gut microbiome. These results suggest that exercise training can prevent physical frailty or cognitive dysfunction by altering the gut microbiome. However, the exact mechanism by which these effects occur is not yet clear. Further studies are needed to determine whether exercise training can prevent age-related diseases by balancing the gut microbiome.