Diagnostic and predictive abilities of myokines in patients with heart failure.

Myokines are defined as a heterogenic group of numerous cytokines, peptides and metabolic derivates, which are expressed, synthesized, produced, and released by skeletal myocytes and myocardial cells and exert either auto- and paracrine, or endocrine effects. Previous studies revealed that myokines play a pivotal role in mutual communications between skeletal muscles, myocardium and remote organs, such as brain, vasculature, bone, liver, pancreas, white adipose tissue, gut, and skin. Despite several myokines exert complete divorced biological effects mainly in regulation of skeletal muscle hypertrophy, residential cells differentiation, neovascularization/angiogenesis, vascular integrity, endothelial function, inflammation and apoptosis/necrosis, attenuating ischemia/hypoxia and tissue protection, tumor growth and malignance, for other occasions, their predominant effects affect energy homeostasis, glucose and lipid metabolism, adiposity, muscle training adaptation and food behavior. Last decade had been identified 250 more myokines, which have been investigating for many years further as either biomarkers or targets for heart failure management. However, only few myokines have been allocated to a promising tool for monitoring adverse cardiac remodeling, ischemia/hypoxia-related target-organ dysfunction, microvascular inflammation, sarcopenia/myopathy and prediction for poor clinical outcomes among patients with HF. This we concentrate on some most plausible myokines, such as myostatin, myonectin, brain-derived neurotrophic factor, muslin, fibroblast growth factor 21, irisin, leukemia inhibitory factor, developmental endothelial locus-1, interleukin-6, nerve growth factor and insulin-like growth factor-1, which are suggested to be useful biomarkers for HF development and progression.

Comparative Analysis of Myokines and Bone Metabolism Markers in Prepubertal Vegetarian and Omnivorous Children.

The role of bone and muscle as endocrine organs may be important contributing factors for children's growth and development. Myokines, secreted by muscle cells, play a role in regulating bone metabolism, either directly or indirectly. Conversely, markers of bone metabolism, reflecting the balance between bone formation and bone resorption, can also influence myokine secretion. This study investigated a panel of serum myokines and their relationships with bone metabolism markers in children following vegetarian and omnivorous diets. A cohort of sixty-eight healthy prepubertal children, comprising 44 vegetarians and 24 omnivores, participated in this study. Anthropometric measurements, dietary assessments, and biochemical analyses were conducted. To evaluate the serum concentrations of bone markers and myokines, an enzyme-linked immunosorbent assay (ELISA) was used. The studied children did not differ regarding their serum myokine levels, except for a higher concentration of decorin in the vegetarian group (p = 0.020). The vegetarians demonstrated distinct pattern of bone metabolism markers compared to the omnivores, with lower levels of N-terminal propeptide of type I procollagen (P1NP) (p = 0.001) and elevated levels of C-terminal telopeptide of type I collagen (CTX-I) (p = 0.018). Consequently, the P1NP/CTX-I ratio was significantly decreased in the vegetarians. The children following a vegetarian diet showed impaired bone metabolism with reduced bone formation and increased bone resorption. Higher levels of decorin, a myokine involved in collagen fibrillogenesis and essential for tissue structure and function, may suggest a potential compensatory mechanism contributing to maintaining bone homeostasis in vegetarians. The observed significant positive correlations between myostatin and bone metabolism markers, including P1NP and soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), suggest an interplay between muscle and bone metabolism, potentially through the RANK/RANKL/OPG signaling pathway.

Serum myostatin is associated with central-to-peripheral arterial stiffness gradient in healthy adolescents. The MACISTE Study.

BACKGROUND: myostatin is a protein compound structurally related to the TGF-beta protein, which plays a pivotal role in regulating muscle growth and extracellular matrix production. exerts both profibrotic and antihypertrophic effects on vascular smooth muscle cells. Aim of the study was to explore the potential association between serum myostatin levels (sMSTN) and carotid-femoral pulse-wave velocity (cf-PWV), carotid-radial pulse wave velocity (cr-PWV), and their ratio (PWVr), in a cohort of healthy adolescents. METHODS: a cohort of 128 healthy subjects (mean age 17±2 years, 59% male) was randomly selected from participants to the MACISTE (Metabolic And Cardiovascular Investigation at School, TErni) study. sMSTN was assessed utilizing an enzyme-linked immunosorbent assay. PWVs were measured in the supine position using high-fidelity applanation tonometry. RESULTS: The mean cf-PWV was 5.1±0.9 m/s, cr-PWV was 6.9±0.9 m/s, PWVr was 0.75±0.12. PWVr exhibited a linear increase across increasing quartiles of sMSTN (0.71±0.1, 0.74±0.1, 0.7±0.1, 0.77±0.1, p for trend=0.03), whereas the association between sMSTN and each single component of PWVr (cf-PWV, cr-PWV) did not attain statistical significance. Quartiles of sMSTN displayed a positive trend with serum HDL-cholesterol (p=0.01) and a negative one with LDL-cholesterol (p=0.01). In a multivariate linear model, the association between PWVr and sMSTN was independent from SBP values, age, sex, heart rate, BMI, HDL-cholesterol and HOMA Index. CONCLUSIONS: In healthy adolescents, sMSTN showed independent associations with PWVr, a measure of central-to-peripheral arterial stiffness gradient. sMSTN may exert differential effects on the structural and functional properties of the arterial wall.

Diet Based on Pereskia aculeata Miller Flour Increases Muscle Volume and Modulates the Expression of Myokines in Mice Subjected to Resistance Training.

The study aimed to evaluate the effects of Pereskia aculeata Miller (ora-pro-nobis [OPN]) flour on body and biochemical parameters, thermogenic activity, and molecular expression of markers in the muscle tissue of mice subjected to resistance training (RT). Twelve mice were randomly assigned to two groups (n=6 animals/group): G1: control (Control) fed a standard diet + RT and G2: experimental (OPN) fed a diet based on OPN flour + RT. The RT consisted of a 6-week program using a vertical ladder combined with a fixed weight attached to the animal. Several parameters were measured, including assessment of body composition, biochemical markers, thermogenic activity, and molecular (mRNA expression of interleukin (IL)-6, fibronectin type III domain-containing protein 5 (FNDC5), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). The OPN group exhibited a decrease in body weight and visceral adiposity, higher energy expenditure, and lipid oxidation rate. In addition, it was observed an increase in muscle volume and in mRNA expression levels of IL-6, FNDC5, PGC-1α, and TFAM. These findings suggest that OPN flour could be a nutritional option to enhance performance in RT.

Enhancing circulatory myokines and extracellular vesicle uptake with targeted exercise in patients with prostate cancer (the MYEX trial): a single-group crossover study.

INTRODUCTION: Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with localised or advanced PCa. METHODS: A single-group cross-over design will be used for patients at opposite ends of the disease spectrum. A total of 32 patients (localised PCa, n = 16; metastatic castrate-resistant PCa, n = 16) will be recruited while capitalising on two ongoing studies. Ethics amendment has been approved for two ongoing trials to share data, implement the acute exercise sessions, and collect additional blood samples from patients. The patients will undertake two exercise sessions (aerobic only and resistance only) in random order one week apart. Blood will be collected before, after, and 30 min post-exercise. Circulating/EV-contained myokine levels (irisin, IL-6, IL-15, FGF-21, and SPARC) and plasma skeletal muscle-induced EVs will be measured using ELISA and flow cytometry. PCa cell line growth with or without collected plasma will be examined using PCa cell lines (LNCaP, DU-145, and PC-3), while evaluating cellular uptake of EVs. Ethics amendments have been approved for two capitalising studies to share data, implement acute exercise sessions and collect additional samples from the patients. DISCUSSION: If findings show a differential impact of exercise mode on the establishment of an anti-cancer systemic environment, this will provide fundamental knowledge for developing targeted exercise prescriptions for patients with PCa across different disease stages. Findings will be reported in peer-reviewed publications and scientific conferences, in addition to working with national support groups to translate findings for the broader community. TRIAL REGISTRATION: The registration for the two capitalising studies are NCT02730338 and ACTRN12618000225213.

Interaction between inflammatory bowel disease, physical activity, and myokines: Assessment of serum irisin levels.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, showed a wide spectrum of intestinal and extra-intestinal manifestations, which rendered the patients physically inactive and impaired their quality of life. It has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those patients. Irisin is one member of the myokines secreted by muscle contraction during exercise and could be used as an anti-inflammatory biomarker in assessing the physical activity of IBD patients. In addition, experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental colitis. Furthermore, irisin produces changes in the diversity of the microbiota. Therefore, endogenous or exogenous irisin, via its anti-inflammatory effects, will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.

Effects of Resistance Exercise and Essential Amino Acid Intake on Muscle Quality, Myokine, and Inflammation Factors in Young Adult Males.

BACKGROUND: Recently, many studies have been devoted to discovering nutrients for exercise-like effects. Resistance exercise and the intake of essential amino acids (EAAs) are known to be factors that can affect muscle mass and strength improvement. The purpose of this study was to investigate changes in muscle quality, myokines, and inflammation in response to resistance exercise and EAA supplementation. METHODS: Thirty-four males volunteered to participate in this study. They were assigned to four groups: (1) placebo (CO), (2) resistance exercise (RE), (3) EAA supplementation, and (4) RE + EAA supplementation. Body composition, muscle quality, myokines, and inflammation were measured at baseline and four weeks after treatment. RESULTS: Lean body fat had decreased in both RE and RE + EAA groups. Lean body mass had increased in only the RE + EAA group. In all groups except for CO, irisin, myostatin A, and TNF-α levels had decreased. The grip strength of the right hand and trunk flexion peak torque increased in the RE group. The grip strength of the left hand, trunk flexion peak torque, and knee flexion peak torque of the left leg were increased in RE + EAA. CONCLUSIONS: RE, EAA, and RE + EAA could effectively improve the muscle quality, myokine, and inflammation factors of young adult males. This finding highlights the importance of resistance exercise and amino acid intake.

Role of Myostatin in Rheumatoid Arthritis: A Review of the Clinical Impact.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects synovial joints and that frequently involves extra-articular organs. A multiplicity of interleukins (IL) participates in the pathogenesis of RA, including IL-6, IL-1ß, transforming growth factor-beta (TGF-ß), and tumor necrosis factor (TNF)-α; immune cells such as monocytes, T and B lymphocytes, and macrophages; and auto-antibodies, mainly rheumatoid factor and anti-citrullinated protein antibodies (ACPAs). Skeletal muscle is also involved in RA, with many patients developing muscle wasting and sarcopenia. Several mechanisms are involved in the myopenia observed in RA, and one of them includes the effects of some interleukins and myokines on myocytes. Myostatin is a myokine member of the TGF-ß superfamily; the overproduction of myostatin acts as a negative regulator of growth and differentiates the muscle fibers, limiting their number and size. Recent studies have identified abnormalities in the serum myostatin levels of RA patients, and these have been found to be associated with muscle wasting and other manifestations of severe RA. This review analyzes recent information regarding the relationship between myostatin levels and clinical manifestations of RA and the relevance of myostatin as a therapeutic target for future research.

A combination of myokines and genistein suppresses cancer stemness in MCF-7 human breast cancer cells.

BACKGROUND/OBJECTIVES: Breast cancer is considered a serious health issue worldwide and is influenced by risk factors, including physical inactivity and unhealthy diet. Myokines secreted by muscles during physical activity play a crucial role in cancer development and the immune system. Genistein (Gen), an isoflavone primarily in legumes, induces anti-cancer activity by regulating cancer stem cells (CSCs). Therefore, this study investigated the potential anti-cancer effect of a combination of myokine and Gen on the human breast cancer MCF-7 cells. MATERIALS/METHODS: MCF-7, a human breast cancer cell line, was used for in vitro study. The cell viability of MCF-7 cells was evaluated in response to treatment with myokines, irisin (Iri), oncostatin M (OSM), and Gen using the MTT assay. Clonogenic and sphere formation assays were used to evaluate the self-renewal capacity of breast CSCs. The mRNA expression levels of stem cell markers were analyzed in MCF-7 breast cancer cells. RESULTS: Administering Iri or OSM with Gen significantly inhibited the self-renewal capacity of MCF-7 cells. In addition, mRNA expression of breast CSC markers SOX2 and OCT4, which are characteristic of CSCs, was suppressed by both myokine and Gen. However, combining Iri or OSM with Gen was the most effective treatment. CONCLUSION: These results suggested that combining Iri or OSM with Gen has an additive effect on breast CSCs by regulating self-renewal capacity and expression of CSCs markers. Therefore, the combination of myokines and Gen may have the therapeutic potential for treating breast cancer and improving the quality of life of cancer patients.

Skeletal muscle as a pro- and anti-inflammatory tissue: insights from children to adults and ultrasound findings.

Previously regarded as a movement and posture control agent, the skeletal muscle is now recognized as an endocrine organ that may affect systemic inflammation and metabolic health. The discovery of myokines such as IL-6, released from skeletal muscle in response to physical exercise, is now one of the most recent insights. Myokines are the mediators of the balance between the pro-inflammatory and anti-inflammatory responses. This underscores the muscle function as a determinant of good health and prevention of diseases. Advances in ultrasound technology improved evaluation of muscle thickness, composition, and determining fat distribution. Combining imaging with molecular biology, researchers discovered the complicated interplay between muscle function, cytokine production and general health effects.The production of myokines with exercise showcasing the adaptability of muscles to high-stress conditions and contributing to metabolism and inflammation regulation. These findings have significant implications in order to provide improvement in metabolic and inflammatory diseases.

The Identification and Evaluation of Interleukin-7 as a Myokine Biomarker for Peripheral Artery Disease Prognosis.

Background/Objectives: Myokines have been demonstrated to be associated with cardiovascular diseases; however, they have not been studied as biomarkers for peripheral artery disease (PAD). We identified interleukin-7 (IL-7) as a prognostic biomarker for PAD from a panel of myokines and developed predictive models for 2-year major adverse limb events (MALEs) using clinical features and plasma IL-7 levels. Methods: A prognostic study was conducted with a cohort of 476 patients (312 with PAD and 164 without PAD) that were recruited prospectively. Their plasma concentrations of five circulating myokines were measured at recruitment, and the patients were followed for two years. The outcome of interest was two-year MALEs (composite of major amputation, vascular intervention, or acute limb ischemia). Cox proportional hazards analysis was performed to identify IL-7 as the only myokine that was associated with 2-year MALEs. The data were randomly divided into training (70%) and test sets (30%). A random forest model was trained using clinical characteristics (demographics, comorbidities, and medications) and plasma IL-7 levels with 10-fold cross-validation. The primary model evaluation metric was the F1 score. The prognostic model was used to classify patients into low vs. high risk of developing adverse limb events based on the Youden Index. Freedom from MALEs over 2 years was compared between the risk-stratified groups using Cox proportional hazards analysis. Results: Two-year MALEs occurred in 28 (9%) of patients with PAD. IL-7 was the only myokine that was statistically significantly correlated with two-year MALE (HR 1.56 [95% CI 1.12-1.88], p = 0.007). For the prognosis of 2-year MALEs, our model achieved an F1 score of 0.829 using plasma IL-7 levels in combination with clinical features. Patients classified as high-risk by the predictive model were significantly more likely to develop MALEs over a 2-year period (HR 1.66 [95% CI 1.22-1.98], p = 0.006). Conclusions: From a panel of myokines, IL-7 was identified as a prognostic biomarker for PAD. Using a combination of clinical characteristics and plasma IL-7 levels, we propose an accurate predictive model for 2-year MALEs in patients with PAD. Our model may support PAD risk stratification, guiding clinical decisions on additional vascular evaluation, specialist referrals, and medical/surgical management, thereby improving outcomes.

Myokine Secretion following an Aerobic Exercise Intervention in Individuals with Type 2 Diabetes with or without Exercise Resistance.

Type 2 diabetes (T2D) is characterized by muscle metabolic dysfunction that exercise can minimize, but some patients do not respond to an exercise intervention. Myokine secretion is intrinsically altered in patients with T2D, but the role of myokines in exercise resistance in this patient population has never been studied. We sought to determine if changes in myokine secretion were linked to the response to an exercise intervention in patients with T2D. The participants followed a 10-week aerobic exercise training intervention, and patients with T2D were grouped based on muscle mitochondrial function improvement (responders versus non-responders). We measured myokines in serum and cell-culture medium of myotubes derived from participants pre- and post-intervention and in response to an in vitro model of muscle contraction. We also quantified the expression of genes related to inflammation in the myotubes pre- and post-intervention. No significant differences were detected depending on T2D status or response to exercise in the biological markers measured, with the exception of modest differences in expression patterns for certain myokines (IL-1ß, IL-8, IL-10, and IL-15). Further investigation into the molecular mechanisms involving myokines may explain exercise resistance with T2D; however, the role in metabolic adaptations to exercise in T2D requires further investigation.

Early Movement Restriction Affects FNDC5/Irisin and BDNF Levels in Rat Muscle and Brain.

Interaction with the environment appears necessary for the maturation of sensorimotor and cognitive functions in early life. In rats, a model of sensorimotor restriction (SMR) from postnatal day 1 (P1) to P28 has shown that low and atypical sensorimotor activities induced the perturbation of motor behavior due to muscle weakness and the functional disorganization of the primary somatosensory and motor cortices. In the present study, our objective was to understand how SMR affects the muscle-brain dialogue. We focused on irisin, a myokine secreted by skeletal muscles in response to exercise. FNDC5/irisin expression was determined in hindlimb muscles and brain structures by Western blotting, and irisin expression in blood and cerebrospinal fluid was determined using an ELISA assay at P8, P15, P21 and P28. Since irisin is known to regulate its expression, Brain-Derived Neurotrophic Factor (BDNF) levels were also measured in the same brain structures. We demonstrated that SMR increases FNDC5/irisin levels specifically in the soleus muscle (from P21) and also affects this protein expression in several brain structures (as early as P15). The BDNF level was increased in the hippocampus at P8. To conclude, SMR affects FNDC5/irisin levels in a postural muscle and in several brain regions and has limited effects on BDNF expression in the brain.

Beyond muscles: Investigating immunoregulatory myokines in acute resistance exercise - A systematic review and meta-analysis.

Myokines, released from the muscle, enable communication between the working muscles and other tissues. Their release during physical exercise is assumed to depend on immune-hormonal-metabolic interactions concerning mode (endurance or resistance exercise), duration, and intensity. This meta-analysis aims to examine the acute changes of circulating myokines inducing immunoregulatory effects caused by a bout of resistance exercise and to consider potential moderators of the results. Based on this selection strategy, a systematic literature search was conducted for resistance exercise intervention studies measuring interleukin (IL-) 6, IL-10, IL-1ra, tumor necrosis factor (TNF-) α, IL-15, IL-7, transforming growth factor (TGF-) ß1, and fractalkines (FKN) before and immediately after resistance exercise in healthy individuals. Random-effects meta-analysis was performed for each myokine. We identified a moderate positive effect of resistance exercise for IL-6 and IL-1ra. Regarding IL-15 and TNF-α, small to moderate effects were found. For IL-10, no significant effect was observed. Due to no data, meta-analyses for IL-7, TGF-ß1, and FKN could not be performed. No moderators (training status, type of exercise, risk of bias, age, sex, time of day, exercise volume, exercise intensity, exercise dose) of the results were detected for all tested myokines. Taken together, this systematic review and meta-analysis showed immediate positive effects of an acute resistance exercise session on IL-6, IL-1ra, TNF-α, and IL-15 levels.

Associations of Serum Irisin and Fibroblast Growth Factor-21 Levels With Bone Mineral Characteristics in Eumenorrheic Adolescent Athletes With Different Training Activity Patterns.

PURPOSE: To describe serum irisin and fibroblast growth factor-21 (FGF-21) concentrations in healthy female adolescents with different training activity patterns and their associations with bone mineral properties and metabolic markers. METHODS: A total of 62 adolescent girls aged 14-18 years were recruited: 22 rhythmic gymnasts, 20 swimmers, and 20 untrained controls. Bone mineral characteristics by dual-energy X-ray absorptiometry, daily energy intake by dietary recall, serum irisin, FGF-21, undercarboxylated osteocalcin, and C-terminal telopeptide of type I collagen were measured in all girls. RESULTS: Whole body and lumbar spine areal bone mineral density and lumbar spine bone mineral content were higher in the rhythmic gymnasts group compared with swimmers and untrained controls groups (P < .05). Serum irisin, FGF-21, undercarboxylated osteocalcin, and C-terminal telopeptide of type I collagen levels were not significantly different between the groups. In the rhythmic gymnasts group, serum FGF-21 concentration was positively correlated with lumbar spine areal bone mineral density independently of confounding factors (r = .51; P = .027). CONCLUSIONS: Serum irisin and FGF-21 levels were not different between adolescent eumenorrheic girls with different training activity patterns. FGF-21 was positively associated with lumbar spine areal bone mineral density, which predominantly consists of trabecular bone in adolescent rhythmic gymnasts.

The Role of the Myokine Irisin in the Protection and Carcinogenesis of the Gastrointestinal Tract.

Recently discovered irisin, a member of the myokines family, is a potential mediator of exercise-induced energy metabolism and a factor promoting browning of the white adipose tissue. Recent evidence indicates that this myokine, released from contracting muscles, can mediate the beneficial effects of exercise on health. Irisin may be a potential therapeutic agent against obesity and has been shown to play an important role in the protection of various cells, tissues, and organs due to its anti-inflammatory, antioxidative, and anti-cancer properties. Our aim was to review the recent experimental and clinical studies on irisin and its expression, release into the bloodstream, tissue targets, and potential contribution to the protective effects of exercise in the gastrointestinal tract. Particular emphasis was placed on inflammatory bowel disease, intestinal ischemia/reperfusion injury, periodontitis, and other digestive tract disorders, including carcinogenesis. Overall, irisin holds significant potential as a novel target molecule, offering a safe and therapeutic approach to treating various gastrointestinal diseases.

Circulating levels of irisin and Meteorin-like protein in PCOS and its correlation with metabolic parameters.

INTRODUCTION: Research on obesity, which results from excessive food consumption and sedentary lifestyle, has focused on increasing energy expenditure. Recently, muscle tissue is being investigated as an endocrine active organ, secreting molecules called myokines. Multiple studies have been performed to assess myokine levels in various disorders, including polycystic ovary syndrome (PCOS) and metabolic syndrome. Irisin and Meteorin-like protein (Metrnl) are particles which, among others, are suggested to play an important role in adipose tissue browning and improving insulin sensitivity. MATERIAL AND METHODS: The study population consisted of 31 women with PCOS and 18 healthy individuals. PCOS was diagnosed based on revised 2003 Rotterdam criteria. Multiple anthropometrical, hormonal, and biochemical parameters were assessed, including oral glucose tolerance test and body composition with dual energy X-ray absorptiometry. Serum levels of irisin and Metrnl were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: There were no differences between the PCOS and control groups according to age, body mass index (BMI), waist-to-hip ratio (WHR), fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR), or body mass composition. Assessment of Metrnl and irisin concentrations revealed no significant differences between PCOS and healthy women. The irisin level was negatively correlated with BMI, body fat mass, fasting glucose, and insulin concentrations. No relationship between Metrnl level and metabolic parameters was found. CONCLUSIONS: Although irisin seems to be a promising biomarker, inconsistent research limits its value in clinical use in the assessment or treatment of obesity. Metrnl level was not affected in the study population, but it might be connected to the severity of metabolic disturbances.

Myokines and Biomarkers of Frailty in Older Inpatients with Undernutrition: A Prospective Study.

BACKGROUND: Population aging might increase the prevalence of undernutrition in older people, which increases the risk of frailty. Numerous studies have indicated that myokines are released by skeletal myocytes in response to muscular contractions and might be associated with frailty. This study aimed to evaluate whether myokines are biomarkers of frailty in older inpatients with undernutrition. METHODS: The frailty biomarkers were extracted from the Gene Expression Omnibus and Genecards datasets. Relevant myokines and health-related variables were assessed in 55 inpatients aged ≥ 65 years from the Peking Union Medical College Hospital prospective longitudinal frailty study. Serum was prepared for enzyme-linked immunosorbent assay using the appropriate kits. Correlations between biomarkers and frailty status were calculated by Spearman's correlation analysis. Multiple linear regression was performed to investigate the association between factors and frailty scores. RESULTS: The prevalence of frailty was 13.21%. The bioinformatics analysis indicated that leptin, adenosine 5'-monophosphate-activated protein kinase (AMPK), irisin, decorin, and myostatin were potential biomarkers of frailty. The frailty group had significantly higher concentrations of leptin, AMPK, and MSTN than the robust group (p < 0.05). AMPK was significantly positively correlated with frailty (p < 0.05). The pre-frailty and frailty groups had significantly lower concentrations of irisin than the robust group (p < 0.05), whereas the DCN concentration did not differ among the groups. Multiple linear regression suggested that the 15 factors influencing the coefficients of association, the top 50% were the ADL score, MNA-SF score, serum albumin concentration, urination function, hearing function, leptin concentration, GDS-15 score, and MSTN concentration. CONCLUSIONS: Proinflammatory myokines, particularly leptin, myostatin, and AMPK, negatively affect muscle mass and strength in older adults. ADL and nutritional status play major roles in the development of frailty. Our results confirm that identification of frailty relies upon clinical variables, myokine concentrations, and functional parameters, which might enable the identification and monitoring of frailty.

Resistance exercise effects on hippocampus subfield volumes and biomarkers of neuroplasticity and neuroinflammation in older adults with low and high risk of mild cognitive impairment: a randomized controlled trial.

Physical exercise is suggested to promote hippocampal neuroplasticity by increasing circulating neurotrophic and anti-inflammatory factors. Our aim was to explore the interplay between the effect of progressive resistance exercise on blood biomarker levels, hippocampal neurometabolite levels and hippocampal volume in older adults with a low compared to a high risk of mild cognitive impairment (MCI). Seventy apparently healthy male/female older adults (aged 60-85 years old) were randomly allocated to a 12 week lower limb progressive resistance or no intervention, stratified for low (< 26/30) or high (≥ 26/30) Montreal Cognitive Assessment (MoCA) score, indicating MCI risk. Outcome measures were blood levels of insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6) or kynurenine (KYN); hippocampal total and subfield volumes of the cornu ammonis 1 (CA1) and 4 (CA4), subiculum, presubiculum, and dentate gyrus measured with magnetic resonance imaging (MRI); and hippocampus neurometabolites including total N-acetylaspartate (NAA), myo-inositol (mIns), and total creatine (Cr) measured with proton magnetic resonance spectroscopy (1H-MRS). We evaluated the intervention effect, cognitive status effect, their interaction and the bivariate relationship between exercise-induced changes between the outcome measures. Higher kynurenine levels (p = 0.015) and lower subiculum volumes (p = 0.043) were found in older adults with high MCI risk compared to older adults with low MCI risk. Exercise-induced CA1 volume changes were negatively correlated with hippocampal tNAA/mIns level changes (r = -0.605, p = 0.006). This study provides valuable insight in the multifactorial processes related to resistance training in older adults with low or high MCI risk.