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While chemotherapy treatment can be lifesaving, it also has adverse effects that negatively impact the quality of life. To investigate the effects of doxorubicin chemotherapy on body weight loss, strength and muscle mass loss, and physical function impairments, all key markers of cachexia, sarcopenia, and frailty. Seventeen C57/BL/6 mice were allocated into groups. 1) Control (n = 7): mice were exposed to intraperitoneal (i.p.) injections of saline solution. 2) Dox (n = 10): mice were exposed to doxorubicin chemotherapy cycles (total dose of 18 mg/kg divided over 15 days). The body weight loss and decreased food intake were monitored to assess cachexia. To assess sarcopenia, we measured muscle strength loss using a traction method and evaluated muscle atrophy through histology of the gastrocnemius muscle. To evaluate physical function impairments and assess frailty, we employed the open field test to measure exploratory capacity. Doxorubicin administration led to the development of cachexia, as evidenced by a significant body weight loss (13%) and a substantial decrease in food intake (34%) over a 15-day period. Furthermore, 90% of the mice treated with doxorubicin exhibited sarcopenia, characterized by a 20% reduction in traction strength (p<0,05), a 10% decrease in muscle mass, and a 33% reduction in locomotor activity. Importantly, all mice subjected to doxorubicin treatment were considered frail based on the evaluation of their overall condition and functional impairments. The proposed model holds significant characteristics of human chemotherapy treatment and can be useful to understand the intricate relationship between chemotherapy, cachexia, sarcopenia, and frailty.

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BACKGROUND: Sarcopenia is a syndrome associated with aging that causes progressive loss of skeletal muscle mass and muscle function. In this pilot study, we compared the effectiveness of elastic band training regarding group-based dance on fat mass, fat-free mass, handgrip strength (HGS; dominant and non-dominant hand), leg strength, timed up-and-go (TUG) and walking speed in older women with sarcopenia. METHODS: This is a randomized controlled trial, single-blind, repeated measures of parallel groups (elastic band group: EBG, n = 21; group-based dance: GBD, n = 19), and a quantitative methodology. Three 60-minute sessions per week for 12 weeks were dedicated to the interventions with pre- and post-assessments. A two-factor mixed analysis of variance (ANOVA) model with repeated measures was performed to measure the group×time effect. RESULTS: A significant interaction revealed for fat-free mass (F1,16= 18.91; p < 0.001; EBG + 10.9% vs. GBD - 1.97%), HGS dominant hand (F1,16= 7.44; p = 0.014; EBG + 10.9% vs. GBD + 0.59%), HGS non-dominant hand (F1,16= 6.41; p = 0.022; EBG + 10.21% vs. GBD + 3.80%), leg strength (F1,16= 17.98; p < 0.001; EBG + 9.1% vs. GBD + 3.83%), TUG (F1,16= 7.52; p = 0.014; EBG - 14.7% vs. GBD - 1.0%) and walking speed (F1,16 = 6.40; p = 0.019; EBG - 7.6% vs. GBD - 4.35%) in favor of EBG. CONCLUSION: Elastic band training produces significantly greater responses on physical-functional performance regarding group-based dance in older women with sarcopenia. On the other hand, the EBG revealed a significant improvement in fat-free mass and upper and lower limb muscle strength, as well as a significant decrease time in TUG, and walking speed. Elastic band exercise is a safe, easy, affordable, and effective physical activity strategy, according to the findings.

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BACKGROUND: Skeletal muscle is sensitive to bile acids (BA) because it expresses the TGR5 receptor for BA. Cholic (CA) and deoxycholic (DCA) acids induce a sarcopenia-like phenotype through TGR5-dependent mechanisms. Besides, a mouse model of cholestasis-induced sarcopenia was characterised by increased levels of serum BA and muscle weakness, alterations that are dependent on TGR5 expression. Mitochondrial alterations, such as decreased mitochondrial potential and oxygen consumption rate (OCR), increased mitochondrial reactive oxygen species (mtROS) and unbalanced biogenesis and mitophagy, have not been studied in BA-induced sarcopenia. METHODS: We evaluated the effects of DCA and CA on mitochondrial alterations in C2C12 myotubes and a mouse model of cholestasis-induced sarcopenia. We measured mitochondrial mass by TOM20 levels and mitochondrial DNA; ultrastructural alterations by transmission electronic microscopy; mitochondrial biogenesis by PGC-1α plasmid reporter activity and protein levels by western blot analysis; mitophagy by the co-localisation of the MitoTracker and LysoTracker fluorescent probes; mitochondrial potential by detecting the TMRE probe signal; protein levels of OXPHOS complexes and LC3B by western blot analysis; OCR by Seahorse measures; and mtROS by MitoSOX probe signals. RESULTS: DCA and CA caused a reduction in mitochondrial mass and decreased mitochondrial biogenesis. Interestingly, DCA and CA increased LC3II/LC3I ratio and decreased autophagic flux concordant with raised mitophagosome-like structures. In addition, DCA and CA decreased mitochondrial potential and reduced protein levels in OXPHOS complexes I and II. The results also demonstrated that DCA and CA decreased basal, ATP-linked, FCCP-induced maximal respiration and spare OCR. DCA and CA also reduced the number of cristae. In addition, DCA and CA increased the mtROS. In mice with cholestasis-induced sarcopenia, TOM20, OXPHOS complexes I, II and III, and OCR were diminished. Interestingly, the OCR and OXPHOS complexes were correlated with muscle strength and bile acid levels. CONCLUSION: Our results showed that DCA and CA decreased mitochondrial mass, possibly by reducing mitochondrial biogenesis, which affects mitochondrial function, thereby altering potential OCR and mtROS generation. Some mitochondrial alterations were also observed in a mouse model of cholestasis-induced sarcopenia characterised by increased levels of BA, such as DCA and CA.

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BACKGROUND: Skeletal muscle generates force and movements and maintains posture. Under pathological conditions, muscle fibers suffer an imbalance in protein synthesis/degradation. This event causes muscle mass loss and decreased strength and muscle function, a syndrome known as sarcopenia. Recently, our laboratory described secondary sarcopenia in a chronic cholestatic liver disease (CCLD) mouse model. Interestingly, the administration of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is an effective therapy for cholestatic hepatic alterations. However, the effect of UDCA on skeletal muscle mass and functionality has never been evaluated, nor the possible involved mechanisms. METHODS: We assessed the ability of UDCA to generate sarcopenia in C57BL6 mice and develop a sarcopenic-like phenotype in C2C12 myotubes and isolated muscle fibers. In mice, we measured muscle strength by a grip strength test, muscle mass by bioimpedance and mass for specific muscles, and physical function by a treadmill test. We also detected the fiber's diameter and content of sarcomeric proteins. In C2C12 myotubes and/or isolated muscle fibers, we determined the diameter and troponin I level to validate the cellular effect. Moreover, to evaluate possible mechanisms, we detected puromycin incorporation, p70S6K, and 4EBP1 to evaluate protein synthesis and ULK1, LC3 I, and II protein levels to determine autophagic flux. The mitophagosome-like structures were detected by transmission electron microscopy. RESULTS: UDCA induced sarcopenia in healthy mice, evidenced by decreased strength, muscle mass, and physical function, with a decline in the fiber's diameter and the troponin I protein levels. In the C2C12 myotubes, we observed that UDCA caused a reduction in the diameter and content of MHC, troponin I, puromycin incorporation, and phosphorylated forms of p70S6K and 4EBP1. Further, we detected increased levels of phosphorylated ULK1, the LC3II/LC3I ratio, and the number of mitophagosome-like structures. These data suggest that UDCA induces a sarcopenic-like phenotype with decreased protein synthesis and autophagic flux. CONCLUSIONS: Our results indicate that UDCA induces sarcopenia in mice and sarcopenic-like features in C2C12 myotubes and/or isolated muscle fibers concomitantly with decreased protein synthesis and alterations in autophagic flux.

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Muscle atrophy decreases muscle mass with the subsequent loss of muscle function. Among the mechanisms that trigger sarcopenia is mitochondrial dysfunction. Mitochondria, whose primary function is to produce ATP, are dynamic organelles that present the process of formation (mitogenesis) and elimination (mitophagy). Failure of any of these processes contributes to mitochondrial malfunction. Mitogenesis is mainly controlled by Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α), a transcriptional coactivator that regulates the expression of TFAM, which participates in mitogenesis. Mitophagy is a process of selective autophagy. Autophagy corresponds to a degradative pathway of protein complexes and organelles. Liver disease caused sarcopenia and increased bile acids in the blood. We demonstrated that the treatment with cholic (CA) or deoxycholic (DCA) bile acids generates mitochondrial dysfunction and loss of biomass. This work assessed whether CA and DCA alter autophagy and mitogenesis. For this, western blot evaluated the autophagy process by determining the protein levels of the LC3II/LC3I ratio. In addition, we assessed mitogenesis using a luciferase-coupled plasmid reporter for the PGC-1α promoter and the protein levels of TFAM by western blot. Our results indicate that treatment with CA or DCA induces autophagy, represented by an increase in the LC3II/LC3I ratio. In addition, a decreased autophagic flux was observed. On the other hand, when treated with CA or DCA, a decrease in the activity of the PGC-1α promoter was observed. However, the levels of TFAM increased in myotubes incubated with CA and DCA. Our results demonstrate that CA and DCA modulate autophagy ad mitogenesis in C2C12 myotubes.

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Chronic liver diseases are a group of pathologies affecting the liver with high prevalence worldwide. Among them, cholestatic chronic liver diseases (CCLD) are characterized by alterations in liver function and increased plasma bile acids. Secondary to liver disease, under cholestasis, is developed sarcopenia, a skeletal muscle dysfunction with decreased muscle mass, strength, and physical function. CCL5/RANTES is a chemokine involved in the immune and inflammatory response. Indeed, CCL5 is a myokine because it is produced by skeletal muscle. Several studies show that bile acids induce CCL5/RANTES expression in liver cells. However, it is unknown if the expression of CCL5/RANTES is changed in the skeletal muscle of mice with cholestatic liver disease. We used a murine model of cholestasis-induced sarcopenia by intake of hepatotoxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC diet), in which we detected the mRNA levels for ccl5. We determined that mice fed the DDC diet presented high levels of serum bile acids and developed typical features of sarcopenia. Under these conditions, we detected the ccl5 gene expression in diaphragm muscle showing elevated mRNA levels compared to mice fed with a standard diet (chow diet). Our results collectively suggest an increased ccl5 gene expression in the diaphragm muscle concomitantly with elevated serum bile acids and the development of sarcopenia.

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BACKGROUND AND AIMS: Factors associated with the concomitant occurrence of low muscle mass and low muscle radiodensity are unclear. This study investigated whether different skeletal muscle phenotypes are associated with functional impairment, serum inflammatory markers, and survival in patients with incurable cancer. METHODS: Three hundred and twenty-six patients (median age, 60 years; 67.5% female) who had abdominal or pelvic computed tomography (CT) scans up to 30 days before the initial assessment were enrolled in the study. CT images were used for the assessment of skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD). Optimal stratification analysis was used to derive cohort-specific cutoff points to define SMI and SMD groups with a higher risk for mortality (SMI, males <45.0 cm2 /m2 and females <44.0 cm2 /m2 ; SMD, males <34 Hounsfield units [HU] and females <30 HU). Based on these cutoffs, participants were classified into four phenotypes: low-risk SMI + low-risk SMD, high-risk SMI + low-risk SMD, low-risk SMI + high-risk SMD, and high-risk SMI + high-risk SMD. RESULTS: Phenotypes with high-risk SMI or high-risk SMD, especially when combined, were associated with low handgrip strength, poor performance status, higher C-reactive protein, and lower serum albumin levels. The phenotypes with high-risk SMD, regardless of low-risk SMI (hazard ratio [HR], 1.74; 95% CI, 1.05-2.88) or high-risk SMI (HR, 1.99; 95% CI, 1.29-3.05) were associated with higher 90 days' mortality risk. CONCLUSION: In patients with incurable cancer, phenotype groups with high-risk SMI and high-risk SMD, particularly when combined, were associated with worse functional impairment and inflammation. Moreover, high-risk SMD was associated with increased mortality risk.

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BACKGROUND: Skeletal muscle is sensitive to bile acids (BA) because it expresses the TGR5 receptor for BA. Cholic (CA) and deoxycholic (DCA) acids induce a sarcopenia-like phenotype through TGR5-dependent mechanisms. Besides, a mouse model of cholestasis-induced sarcopenia was characterised by increased levels of serum BA and muscle weakness, alterations that are dependent on TGR5 expression. Mitochondrial alterations, such as decreased mitochondrial potential and oxygen consumption rate (OCR), increased mitochondrial reactive oxygen species (mtROS) and unbalanced biogenesis and mitophagy, have not been studied in BA-induced sarcopenia.METHODS: We evaluated the effects of DCA and CA on mitochondrial alterations in C2C12 myotubes and a mouse model of cholestasis-induced sarcopenia. We measured mitochondrial mass by TOM20 levels and mitochondrial DNA; ultrastructural alterations by transmission electronic microscopy; mitochondrial biogenesis by PGC-1α plasmid reporter activity and protein levels by western blot analysis; mitophagy by the co-localisation of the MitoTracker and LysoTracker fluorescent probes; mitochondrial potential by detecting the TMRE probe signal; protein levels of OXPHOS complexes and LC3B by western blot analysis; OCR by Seahorse measures; and mtROS by MitoSOX probe signals. RESULTS: DCA and CA caused a reduction in mitochondrial mass and decreased mitochondrial biogenesis. Interestingly, DCA and CA increased LC3II/LC3I ratio and decreased autophagic flux concordant with raised mitophagosome-like structures. In addition, DCA and CA decreased mitochondrial potential and reduced protein levels in OXPHOS complexes I and II. The results also demonstrated that DCA and CA decreased basal, ATP-linked, FCCP-induced maximal respiration and spare OCR. DCA and CA also reduced the number of cristae. In addition, DCA and CA increased the mtROS. In mice with cholestasis-induced sarcopenia, TOM20, OXPHOS complexes I, II and III, and OCR were diminished. Interestingly, the OCR and OXPHOS complexes were correlated with muscle strength and bile acid levels. CONCLUSION: Our results showed that DCA and CA decreased mitochondrial mass, possibly by reducing mitochondrial biogenesis, which affects mitochondrial function, thereby altering potential OCR and mtROS generation. Some mitochondrial alterations were also observed in a mouse model of cholestasis-induced sarcopenia characterised by increased levels of BA, such as DCA and CA.

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BACKGROUND: Skeletal muscle generates force and movements and maintains posture. Under pathological conditions, muscle fibers suffer an imbalance in protein synthesis/degradation. This event causes muscle mass loss and decreased strength and muscle function, a syndrome known as sarcopenia. Recently, our laboratory described secondary sarcopenia in a chronic cholestatic liver disease (CCLD) mouse model. Interestingly, the administration of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is an effective therapy for cholestatic hepatic alterations. However, the effect of UDCA on skeletal muscle mass and functionality has never been evaluated, nor the possible involved mechanisms. METHODS: We assessed the ability of UDCA to generate sarcopenia in C57BL6 mice and develop a sarcopenic-like phenotype in C2C12 myotubes and isolated muscle fibers. In mice, we measured muscle strength by a grip strength test, muscle mass by bioimpedance and mass for specific muscles, and physical function by a treadmill test. We also detected the fiber's diameter and content of sarcomeric proteins. In C2C12 myotubes and/or isolated muscle fibers, we determined the diameter and troponin I level to validate the cellular effect. Moreover, to evaluate possible mechanisms, we detected puromycin incorporation, p70S6K, and 4EBP1 to evaluate protein synthesis and ULK1, LC3 I, and II protein levels to determine autophagic flux. The mitophagosome-like structures were detected by transmission electron microscopy. RESULTS: UDCA induced sarcopenia in healthy mice, evidenced by decreased strength, muscle mass, and physical function, with a decline in the fiber's diameter and the troponin I protein levels. In the C2C12 myotubes, we observed that UDCA caused a reduction in the diameter and content of MHC, troponin I, puromycin incorporation, and phosphorylated forms of p70S6K and 4EBP1. Further, we detected increased levels of phosphorylated ULK1, the LC3II/LC3I ratio, and the number of mitophagosome-like structures. These data suggest that UDCA induces a sarcopenic-like phenotype with decreased protein synthesis and autophagic flux. CONCLUSIONS: Our results indicate that UDCA induces sarcopenia in mice and sarcopenic-like features in C2C12 myotubes and/or isolated muscle fibers concomitantly with decreased protein synthesis and alterations in autophagic flux.

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BACKGROUND: Women with breast cancer are at risk for the development of sarcopenia and occurrence of fractures. The initial and periodic screening of these conditions can prevent the risks of disability, poor quality of life, and death. The present study investigated the association between sarcopenia phenotypes and fracture risk, assessed by the Fracture Risk Assessment Tool (FRAX) in women with breast cancer. METHODS: Cross-sectional study. It included women aged between 40 and 80 years, diagnosed with Luminal subtype breast cancer, with time of diagnosis ≤ 12 months, who had not started endocrine therapy, did not have metastasis, had not been treated for another malignancy, and had no recurrences. Sociodemographic, habits and lifestyle, clinical, anthropometric, and body composition variables were considered. Muscle strength, skeletal muscle mass, and physical performance were investigated using handgrip strength (HGS), appendicular skeletal muscle mass index (ASMI), and Timed Up and Go test (TUGT), respectively. Fracture risk was assessed using FRAX. Multiple linear regression models were conducted to verify the association between exposure variables and sarcopenia phenotypes. A significance level of p < 0.05 was adopted for all tests using the SPPS 25.0 program. RESULTS: Sixty-two women with a mean age of 58.1 ± 10.4 years were evaluated. Of these, 66.1% self-declared to be non-white, 41.9% and 71.0% did not consume alcohol or smoke, respectively, and 61.3% were insufficiently active. A total of 45.2% had clinical stage II carcinoma and 65.5% had the invasive breast carcinoma histological subtype. There was a predominance of adequacy of HGS (88.7%), ASMI (94.5%), and TUGT (96.8%), as well as low risk of hip fractures (85.5%) and major fractures (82.3%). HGS remained associated with FRAX hip fractures (p = 0.007) and FRAX major fractures (p = 0.007) in the adjusted models, while ASMI was associated with body mass (p < 0.001). CONCLUSIONS: Low muscle strength was the sarcopenia phenotype that remained associated with fracture risk in women with breast cancer, independently of sociodemographic factors, level of physical activity, and clinical factors. In addition to the assessment of probable sarcopenia, this measurement may point out the risk of fractures.

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Sarcopenia is generally an age-related condition that directly impacts the quality of life. It is also related to chronic diseases such as metabolic dysfunction associated with diabetes and obesity. This means that everyone will be vulnerable to sarcopenia at some point in their life. Research to find the precise molecular mechanisms implicated in this condition can increase knowledge for the better prevention, diagnosis, and treatment of sarcopenia. Our work gathered the most recent research regarding inflammation in sarcopenia and new therapeutic agents proposed to target its consequences in pyroptosis and cellular senescence. Finally, we compared dual X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), and ultrasound (US) as imaging techniques to diagnose and follow up on sarcopenia, indicating their respective advantages and disadvantages. Our goal is for the scientific evidence presented here to help guide future research to understand the molecular mechanisms involved in sarcopenia, new treatment strategies, and their translation into clinical practice.

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BACKGROUND: Identifying low skeletal muscle strength (SMS), skeletal muscle mass (SMM) and skeletal muscle quality (SMQ) is pivotal for diagnosing sarcopenia cases. Age-related declines in SMS, SMM, and SMQ are dissimilar between the upper (UL) and lower limbs (LL). Despite this, both UL and LL measures have been used to assess SMS, SMM and SMQ in older adults. However, it is not clear whether there is agreement between UL and LL measures to identify older adults with low SMS, SMM and SMQ. OBJECTIVE: To investigate the agreement between UL and LL measures to identify older adults with low SMS, SMM and SMQ. METHODS: Participants (n = 385; 66.1 ± 5.1 years; 75,4% females) performed the handgrip strength test (HGS) and the 30-s chair stand test (CST) to assess UL- and LL-SMS, respectively. The SMM was assessed by dual-energy X-ray absorptiometry (DXA). The UL-SMQ was determined as: handgrip strength (kgf) ÷ arm SMM (kg). LL-SMQ was determined as: 30-s CST performance (repetitions) ÷ leg SMM (kg). Results below the 25th percentile stratified by sex and age group (60-69 and 70-80 years) were used to determine low SMS, SMM and SMQ. Cohen's kappa coefficient (κ) was used for the agreement analyses. RESULTS: There was a slight and non-significant agreement between UL and LL measures to identify older adults with low SMS (κ = 0.046; 95% CI 0.093-0.185; p = 0.352). There was a moderate agreement to identify low SMM (κ = 0.473; 95% CI 0.371-0.574; p = 0.001) and a fair agreement to identify low SMQ (κ = 0.206; 95% CI 0.082 to 0.330; p = 0.005). CONCLUSION: The agreement between UL and LL measures to identify older adults with low SMS, SMM and SMQ is limited, which might generate different clinical interpretations for diagnosing sarcopenia cases.

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BACKGROUND: Sarcopenia is a progressive and generalized skeletal muscle disorder characterized by muscle weakness, loss of muscle mass, and decline in the capacity of force generation. Aging can cause sarcopenia. Several therapeutic strategies have been evaluated to prevent or alleviate this disorder. One of them is angiotensin 1-7 [Ang-(1-7)], an anti-atrophic peptide for skeletal muscles that regulates decreased muscle mass for several causes, including aging. Another regulator of muscle mass and function is andrographolide, a bicyclic diterpenoid lactone that decreases the nuclear factor kappa B (NF-κB) signaling and attenuates the severity of some muscle diseases. OBJECTIVE: Evaluate the effect of combined administration of Ang-(1-7) with andrographolide on the physical performance, muscle strength, and fiber´s diameter in a murine model of sarcopenia by aging. METHODS: Aged male mice of the C57BL/6J strain were treated with Andrographolide, Ang-(1-7), or combined for three months. The physical performance, muscle strength, and fiber´s diameter were measured. RESULTS: The results showed that aged mice (24 months old) treated with Ang-(1-7) or Andrographolide improved their performance on a treadmill test, muscle strength, and their fiber´s diameter compared to aged mice without treatment. The combined administration of Ang-(1-7) with andrographolide to aged mice has an enhanced synergically effect on physical performance, muscle strength, and fiber´s diameter. CONCLUSION: Our results indicated that in aged mice, the effects of andrographolide and Ang-(1-7) on muscle function, strength, and fiber´s diameter are potentiated.

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BACKGROUND: Age-related mechanisms of sarcopenia associated with vascular function have been recently suggested. This study compared and tested associations between muscle mass and strength, microcirculation, inflammatory biomarkers, and oxidative stress in older adults classified as sarcopenic and non-sarcopenic. METHODS: Thirty-three physically inactive individuals (72±7 yrs) were assigned to age-matched sarcopenic (SG) and non-sarcopenic (NSG) groups. Between-group comparisons were performed for appendicular skeletal mass (ASM), handgrip and isokinetic strength, microvascular function and morphology, C-reactive protein, insulin-like growth factor-1, tumor necrosis factor-alpha, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, endothelin-1, and oxidized low-density lipoprotein. RESULTS: ASM and knee isokinetic strength were lower in SG than NSG (P < 0.05). No difference between groups was found for outcomes of microvascular function and morphology, but log-transformed IL-6 concentration was twice greater in SG vs. NSG (P = 0.02). Correlations between ASM index, handgrip and knee isokinetic strength vs. markers of microcirculatory function, capillary diameters, vascular reactivity, and endothelial injury were found only in SG. CONCLUSION: Decreased ASM index and strength have been associated with microcirculatory profile, indicating that microcirculation impairment may be involved somehow in Sarcopenia development. The inflammation status, particularly elevated IL-6, seems to play an important role in this process.

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BACKGROUND: This study aimed to evaluate the association of body composition with toxicity to first-line chemotherapy and three-year survival in women with ovarian adenocarcinoma. METHODS: We enrolled, in a retrospective cohort, 239 women treated with carboplatin and paclitaxel between 2008 and 2017. Pretreatment computed tomography scans were used to quantify skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), and subcutaneous adipose tissue index (SATI). Chemotherapy doses, related toxicities, potential drug-drug interactions (DDI), and clinical variables were collected from medical records. Outcomes were the number of adverse events ≥ grade 3 toxicity, toxicity-induced modification of treatment (TIMT), and three-year survival. RESULTS: Average age was 56.3 years and 35.1% had myopenia. Almost 33% had TIMT and 51.3% presented any grade 3 toxicity. Potential severe DDI occurred in 48.1% of the patients and 65.1% died three years after the first treatment. The SMD and SATI below the median were independent predictors for the number of adverse events ≥ grade 3 and TIMT. Also, SMD was the only body composition parameter able to predict reduced three-year survival. The SMI was not associated with any of the outcomes. CONCLUSION: Fewer amounts of SATI and low SMD were associated with the occurrence of toxicity to chemotherapy, and the low SMD increased the risk of death in the three years after oncologic treatment.

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Sarcopenia is one of the most common features of cirrhosis, contributing to morbidity and mortality in this population. We aimed to evaluate the effect of melatonin (MLT) and exercise (EX) on the quadriceps muscle in rats with biliary cirrhosis induced by bile duct ligation (BDL). We used 48 males (mean weight = 300 g), divided into eight groups. A 20 mg/Kg MLT dose was administered via i.p. (1 x daily), and the EX, the animals were set to swim in couples for 10 min each day. Upon completion, blood, liver, and quadriceps samples were taken for analysis. In the liver enzymes analysis and comet assay results, a reduction was observed in the groups treated with MLT with/or EX comparing to the BDL group. In the evaluation of substances that react to thiobarbituric acid (TBARS), nitric oxide levels (NO), and tumor necrosis factor-alpha levels (TNF-α), there was a significant increase in the BDL group and a reduction in the treated groups. In the activity of the superoxide dismutase enzyme (SOD) and interleukin-10 levels (IL-10) concentrations, there was a significant increase in the treated groups of the BDL group. Histological analysis revealed muscle hypotrophy in the BDL group in comparison with the control group (CO) and increased muscle mass in the treated groups. There was an increase in weight gain and phase angle in the groups treated with MLT with/or EX comparing to the BDL group. We suggest that treatments may contribute to the reduction of muscle changes in cirrhotic patients.

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BACKGROUND AND OBJECTIVES: The excess of body fat and muscle mass loss in adulthood results in sarcopenic obesity, which is associated with disability and poor physical condition. A relationship among obesity, sarcopenia and oxidative stress also has been established. These aspects limit a good muscle function which is crucial in the independence of older women with and without sarcopenic obesity. This study had as objective to design a moderate intensity exercise program for older women with sarcopenic obesity, and to examine its effects on oxidative damage and physical function. We hypothesized that the exercise program will reduce oxidative damage and to improve the physical function of older women with sarcopenic obesity. METHODS: Thirty healthy women (68 ± 5.05 years old) and 30 women with sarcopenic obesity (68.06 ± 5.75 years old) from the Integral Development of the Family rest home participated in the evaluation. The participants underwent evaluations of body composition, physical fitness (timed up-and-go [TUG] test, reaction time, gait speed, flexibility and muscle strength) and oxidative stress (oxidative damage to lipid and protein as well as evaluation of the antioxidant system) before and after of moderate intensity exercise program. The program consisted of warm-up, flexibility; aerobic exercises of moderate intensity (VO2 max and HR max between 60% and 70%); isotonic exercises of low intensity with progressive weight (250 g of initial weight, with increase every two weeks until reaching 750 g of final weight) and global stretching at the end of each section. The program was monitored on a personal basis and undertaken three times a week over three months. RESULTS: In both groups, the program induced a five-fold increase in muscle strength, an increase in flexibility and improvement of fragility parameters (TUG and gait speed) (P ≤ 0.001, respectively). Furthermore, this exercise program decreased oxidative damage and increased antioxidant defense (P ≤ 0.001) to a greater extent in the sarcopenic group. CONCLUSION: It was concluded that moderate intensity exercise is an effective approach to promote changes in body composition, physical fitness and to reduce oxidative damage in older women with and without sarcopenic obesity. These findings might have important implications for the prevention or treatment of sarcopenic obesity in older people.

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OBJECTIVES: The aim of this study was to determine sensitivity, specificity, and best cutoff point for adductor pollicis muscle thickness (APMT) for diagnosis of sarcopenia in elderly community centers. METHODS: This was a cross-sectional study comprising 321 elderly individuals from four community centers in Cuiabá, Central-West region of Brazil. The main outcome variables were calf circumference (CC; cm) and the APMT (mm). A receiver operating characteristic curve was built to assess the accuracy of APMT having CC as a golden pattern for sarcopenia. The best cutoff point was defined by Youden's J statistic. RESULTS: The area under curve of APMT was 0.70 (95% confidence interval [CI], 0.63-0.76; P < 0.001) for all individuals, 0.74 (95% CI, 0.67-0.81; P < 0.001) for women, and 0.71 (95% CI, 0.58-0.85; P =.01) for men. The best cutoff point defined by Youden's J statistic was 17.63 mm for all individuals, the same for women. and 18.51 mm for men. CONCLUSION: The APMT can be used for the diagnosis of sarcopenia. The optimal cutoff points for APMT are 17.63 mm for women and 18.51 mm for men in elderly communities in the Central-West Region of Brazil.

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Mitochondria are the first-line defense of the cell in the presence of stressing processes that can induce mitochondrial dysfunction. Under these conditions, the activation of two axes is accomplished, namely, (i) the mitochondrial unfolded protein response (UPRmt) to promote cell recovery and survival of the mitochondrial network; (ii) the mitophagy process to eliminate altered or dysfunctional mitochondria. For these purposes, the former response induces the expression of chaperones, proteases, antioxidant components and protein import and assembly factors, whereas the latter is signaled through the activation of the PINK1/Parkin and BNIP3/NIX pathways. These adaptive mechanisms may be compromised during aging, leading to the development of several pathologies including sarcopenia, defined as the loss of skeletal muscle mass and performance; and non-alcoholic fatty liver disease (NAFLD). These age-associated diseases are characterized by the progressive loss of organ function due to the accumulation of reactive oxygen species (ROS)-induced damage to biomolecules, since the ability to counteract the continuous and large generation of ROS becomes increasingly inefficient with aging, resulting in mitochondrial dysfunction as a central pathogenic mechanism. Nevertheless, the role of the integrated stress response (ISR) involving UPRmt and mitophagy in the development and progression of these illnesses is still a matter of debate, considering that some studies indicate that the prolonged exposure to low levels of stress may trigger these mechanisms to maintain mitohormesis, whereas others sustain that chronic activation of them could lead to cell death. In this review, we discuss the available research that contributes to unveil the role of the mitochondrial UPR in the development of sarcopenia, in an attempt to describe changes prior to the manifestation of severe symptoms; and in NAFLD, in order to prevent or reverse fat accumulation and its progression by means of suitable protocols to be addressed in future studies.

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