Doxorubicin causes cachexia, sarcopenia, and frailty characteristics in mice.

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.

Pre and Post-high-intensity Interval Training Delays Colon Tumor Onset in a Syngeneic Mouse Model.

BACKGROUND/AIM: High-intensity interval training (HIIT) can trigger transient anti-tumor cytotoxicity through the mobilization of natural killer cells (NK cells) and myokines. Yet, the effects of HIIT on tumor development and microenvironment are unclear. MATERIALS AND METHODS: Male C57/BL6 mice were administered either MC38 of syngeneic colon cancer cells or vehicle in a single subcutaneous injection. Before injection, the training group completed four weeks of the HIIT program (progressive swimming training, 3/week, 10-12 min, 4-6% of body weight for overload). Following injection, trained mice continued to exercise for two additional weeks. RESULTS: Pre and post-HIIT training was effective in preventing tumor onset (p=0.0065), maintaining body weight gain, and counteracting splenomegaly by 40% compared to the tumor group. However, HIIT had no impact on suppressing tumor growth, modifying final tumor volume, or significantly changing tumor proliferation (Ki-67), connective tissue content, or DNA double-strand damage detected by phospho-histone gamma-H2AX (γ-H2AX). CONCLUSION: Pre and post-HIIT program is feasible for mice carrying a subcutaneous syngeneic tumor and effective in delaying tumor burden; however, HIIT did not alter colon tumor endpoints.

Chemotherapy periodization to maximize resistance training adaptations in oncology.

INTRODUCTION: Engaging in exercise programs during cancer treatment is challenging due to the several chemotherapy-induced side effects. Using a pre-clinical model that mimics chemotherapy treatment, we investigated if a periodized-within-chemotherapy training strategy can maximize resistance training (RT) adaptations such as increasing muscle mass and strength. METHODS: Swiss mice were randomly allocated into one of the following five groups (n = 14): control (C), resistance training (RT), chemotherapy-treated non-exercised group (Ch), resistance training chemotherapy treated (RTCh), and resistance training periodized-within-chemotherapy (RTPCh). Doxorubicin (i.p.) was weekly injected for a total of 3 weeks (total dose of 12 mg/kg). Resistance training consisted of ladder climbing with progressive intensity, three times a week for 3 weeks, during chemotherapy treatment. RTPCh prescriptions considered "bad day" adjustments while RTCh did not. "Bad day" adjustments considered the presence or absence of clinical signs (e.g., severe weight loss, diarrhea, mice refusing to train) to replace RT sessions. At the end of the third week, animals were euthanized. RESULTS: Weekly doxorubicin injection promoted progressive body weight loss, muscle atrophy, strength loss, local oxidative stress, and elevated inflammatory mediators, such as TNF-α and IL-6. Non-periodized-within-chemotherapy RT promoted mild protection against doxorubicin-induced skeletal muscle disturbances; moreover, when periodized-within-chemotherapy was applied, RT prevented elevated skeletal muscle inflammatory mediators and oxidative damage markers and promoted muscle mass and strength gains. CONCLUSION: Considering chemotherapy-induced side effects is a crucial aspect when prescribing resistance exercise during cancer, it will maximize the effectiveness of exercise in enhancing muscle mass and strength.

Effects of lipodystrophy and physical exercise on bioimpedance parameters in people living with HIV: A cross-sectional study.

OBJECTIVE: The aim of this study was to evaluate the effects of lipodystrophy and physical exercise on the parameters of bioimpedance spectroscopy (BIS) and bioimpedance vector analysis (BIVA) of people living with HIV (PLWHIV). METHODS: Seventy patients were divided into two groups: PLWHIV with lipodystrophy (PLWHIV-L) and PLWHIV without lipodystrophy (PLWHIV-NL). The phase angle (PhA) and the BIVA were determined from the values of resistance and reactance collected by the BIS. The percentage of fat mass and lean soft tissue (LST) were determined by dual-energy x-ray absorptiometry. For comparisons between the PLWHIV-L and PLWHIV-NL groups, the t test for independent samples or the Mann-Whitney test was used. From the BIVA, the average of the impedance vectors of the two groups was calculated with the 95% confidence ellipse, and the individual vectors of the patients divided by sex were also compared with the tolerance ellipses of 50%, 75%, and 95% of the healthy reference population. The relationships between the variables of interest were determined by the Pearson or Spearman correlation coefficient and the coefficient of determination. Analysis of covariance was used for comparisons between groups, adjusted for possible confounding variables. RESULTS: PLWIV-L showed better hydration conditions (P <0.01), higher LST (P <0.01), and lower percent of fat mass (P <0.01). No differences in PhA were observed between PLWHIV who practiced or did not practice physical exercise. There was a significant difference between the impedance vectors of the groups with and without lipodystrophy (T = 42.4 and P <0.01). Additionally, most of the patients who were positioned beyond the ellipse limits of 50% of tolerance fell into the areas of edema and cachexia. The extracellular to intracellular water ratio explained 81% of the PhA variations. When PhA was adjusted for height2, fat mass/height2 and LST, it was significantly different between groups of the female sex (PhA: P <0.01). CONCLUSION: Lipodystrophy and the practice of physical exercise do not present direct involvement in the PhA values, with sex, body composition, and hydration variables being the main influences on this variable. BIVA was able to show differences in the body composition of the groups even when the PhA values were similar.

Acute effect of low-load resistance exercise with blood flow restriction on oxidative stress biomarkers: A systematic review and meta-analysis.

BACKGROUND: The purpose of this review was to analyze the acute effects of low-load resistance exercise with blood flow restriction (LLE-BFR) on oxidative stress markers in healthy individuals in comparison with LLE or high-load resistance exercise (HLRE) without BFR. MATERIALS AND METHODS: A systematic review was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. These searches were performed in CENTRAL, SPORTDiscus, EMBASE, PubMed, CINAHL and Virtual Health Library- VHL, which includes Lilacs, Medline and SciELO. The risk of bias and quality of evidence were assessed through the PEDro scale and GRADE system, respectively. RESULTS: Thirteen randomized clinical trials were included in this review (total n = 158 subjects). Results showed lower post-exercise damage to lipids (SMD = -0.95 CI 95%: -1.49 to -0. 40, I2 = 0%, p = 0.0007), proteins (SMD = -1.39 CI 95%: -2.11 to -0.68, I2 = 51%, p = 0.0001) and redox imbalance (SMD = -0.96 CI 95%: -1.65 to -0.28, I2 = 0%, p = 0.006) in favor of LLRE-BFR compared to HLRE. HLRE presents higher post-exercise superoxide dismutase activity but in the other biomarkers and time points, no significant differences between conditions were observed. For LLRE-BFR and LLRE, we found no difference between the comparisons performed at any time point. CONCLUSIONS: Based on the available evidence from randomized trials, providing very low or low certainty of evidence, this review demonstrates that LLRE-BFR promotes less oxidative stress when compared to HLRE but no difference in levels of oxidative damage biomarkers and endogenous antioxidants between LLRE. TRIAL REGISTRATION: Register number: PROSPERO number: CRD42020183204.

Creatine Supplementation Potentiates Exercise Protective Effects against Doxorubicin-Induced Hepatotoxicity in Mice.

We tested the hypothesis that creatine supplementation may potentiate exercise's protective effects against doxorubicin-induced hepatotoxicity. Thirty-eight Swiss mice were randomly allocated into five groups: control (C, n = 7), exercised (Ex, n = 7), treated with doxorubicin (Dox, n = 8), treated with doxorubicin and exercised (DoxEx, n = 8), and treated with doxorubicin, exercised, and supplemented with creatine (DoxExCr, n = 8). Doxorubicin was administered weekly (i.p.) for a total dose of 12 mg/kg. Creatine supplementation (2% added to the diet) and strength training (climbing stairs, 3 times a week) were performed for a total of 5 weeks. The results demonstrated that doxorubicin caused hepatotoxicity, which was evidenced by increased (p < 0.05) hepatic markers of inflammation (i.e., TNF-α and IL-6) and oxidative damage, while the redox status (GSH/GSSG) was reduced. The plasma concentrations of liver transaminases were also significantly (p < 0.05) elevated. Furthermore, doxorubicin-treated animals presented hepatic fibrosis and histopathological alterations such as cellular degeneration and the infiltration of interstitial inflammatory cells. Exercise alone partly prevented doxorubicin-induced hepatotoxicity; thus, when combined with creatine supplementation, exercise was able to attenuate inflammation and oxidative stress, morphological alterations, and fibrosis. In conclusion, creatine supplementation potentiates the protective effects of exercise against doxorubicin-induced hepatotoxicity in mice.

Relationship Between Body Size and Skeletal Age with Muscle Damage in Young Soccer Players.

This study verified the relationship between body size and skeletal age (SA) with the behavior of blood markers of muscle damage and delayed onset muscle soreness (DOMS) after a soccer match in the U-13 and U-15 categories. The sample consisted of 28 soccer players in the U-13 and 16 in the U-15 categories. Creatine kinase (CK), lactate dehydrogenase (LDH), and DOMS were evaluated up to 72 h after the match. Muscle damage was elevated at 0 h in U-13, and from 0 h to 24 h in U-15. DOMS increased from 0 h to 72 h in U-13 and from 0 h to 48 h in U-15. Significant associations of SA and fat-free mass (FFM) with muscle damage markers and DOMS were observed only in U-13, specifically at time 0 h, when SA explained 56% of CK and 48% of DOMS and FFM explained 48% of DOMS. We concluded that in the U-13 category, higher SA is significantly associated with muscle damage markers, and increase in FFM is associated with muscle damage markers and DOMS. Furthermore, U-13 players need 24 h to recover pre-match muscle damage markers and more than 72 h to recover DOMS. In contrast, the U-15 category needs 48 h to recover muscle damage markers and 72 h to recover DOMS.

Statin protects men but not women with HIV against loss of muscle mass, strength, and physical function: a pilot study.

Statins are cholesterol-lowering drugs commonly used among people with HIV, associated with an increased risk of myopathies. Considering that cardiovascular disease, statin therapy, and sarcopenia are independently prevalent in people with HIV, clarity on the potential benefits or harms of statin therapy on muscle health is useful to provide insight into ways to maximize skeletal muscle health and minimize CVD risk in this population. We aimed to study the effects of statin therapy on strength, muscle mass, and physical function parameters in people with HIV. This was a pilot cross-sectional study. People with HIV on continuous statin therapy (n = 52) were paired 1:1 according to age (people with HIV 53.9 ± 8.2 and people with HIV on statins 53.9 ± 8.4 years), sex, body mass index (Body mass index, people with HIV 28.6 ± 5.3 and people with HIV on statins 28.8 ± 6.3 kg/m2), and race with people with HIV not using statin (n = 52). Participants were evaluated for muscle strength (i.e. handgrip strength), lean and fat body mass (using bioelectric impedance analysis), and physical function (i.e. Short Physical Performance Battery-SPPB). Isokinetic strength and appendicular lean mass (using dual-energy X-ray absorptiometry), more accurate strength and body composition measures, were determined in 38% of the participants. Overall, statin usage does not exacerbated loss of muscle strength (32.2 ± 11.5 vs. 30.3 ± 9.6 kg, p > 0.05) muscle mass (7.6 ± 1.8 vs. 7.7 ± 1.1 kg/m2, p > 0.05), and impaired physical performance (10.1 ± 1.8 vs. 9.7 ± 2.1 points, p > 0.05) of PLWH. When analyzed by sex, men living with HIV on statins usage presented higher appendicular muscle mass (28.4 ± 3.1 vs. 26.2 ± 4.9 kg, p < 0.05) handgrip strength (42.1 ± 8.8 vs. 37.1 ± 8.3 kg, p < 0.05) and physical function through SPPB score (10.9 ± 1.3 vs. 9.5 ± 2.1, p < 0.05) than men living with HIV not on statins treatment. The same protection was not observed in women. This data was demonstrated when muscle mass and strength were determined clinically (i.e. handgrip strength and electrical impedance) and when more precise laboratory measurements of muscle mass and strength were conducted (i.e. isokinetic strength and DXA scans). Statin does not exacerbate muscle wasting, strength loss, or muscle dysfunction among people with HIV. Indeed, statins may protect men, but not woman with HIV against HIV and antiretroviral therapy-induced loss of muscle mass and strength.

Effect of Resistance Exercise Order on Cardiovascular Disease Risk Factors in Older Women: A Randomized Controlled Trial.

We compared the effects of two specific resistance training (RT) exercise orders on cardiovascular risk factors. Forty-four untrained older women (>60 years) were randomly assigned to three groups: control (CON, n = 15), multi-joint to single-joint (MJ-SJ, n = 14), and single-joint to multi-joint (SJ-MJ, n = 15) exercise orders. Training groups performed a whole-body RT program (eight exercises, 3 × 10−15 repetitions for each exercise) over 12 weeks in 3 days/week. Body fat, triglycerides, total cholesterol, HDL-c, LDL-c, VLDL-c, glucose, IL-6, IL-10, TNF-α, C-reactive protein, total radical-trapping antioxidant (TRAP), advanced oxidation protein products (AOPP), ferrous oxidation-xylenol (FOX), and nitric oxide concentrations (NOx) were determined pre- and post-intervention. Significant interaction group × time (p < 0.05) revealed reducing fat mass and trunk fat and improvements in glucose, LDL-c, IL-10, TNF-α, C-reactive protein, FOX, and AOPP concentrations in both training groups, without differences between them (p > 0.05). The results suggest that 12 weeks of RT, regardless of exercise order, elicit positive adaptations on body fat and metabolic biomarkers similarly in older women.

Health and sociodemographic factors associated with low muscle strength, muscle mass, and physical performance among people living with HIV.

ABSTRACTThis study examined the factors associated with low muscle strength, muscle mass, and physical performance in 331 people living with HIV. Participants completed handgrip as a strength measure, appendicular skeletal muscle mass using bioimpedance analysis, and chair rise was a physical performance measure. Multivariate logistic regression was used to analyze the association between low values on these measures with sociodemographic, HIV-related factors, and comorbidities. Higher body mass index (BMI) (OR = 0.91; CI = 0.86-0.97) and higher CD4/CD8 ratio (OR = 0.38; 95% CI = 0.18-0.82) were associated with decreased likelihood of low handgrip strength. Being non-employed (OR = 2.08; 95% CI = 1.07-4.06), having hypertension (OR = 2.27; 95% CI = 1.13-4.54) and rheumatism (OR = 5.46; 95% CI = 1.68-17.74) increased the chance of low handgrip strength. Higher BMI (OR = 0.43; 95% CI = 0.34-0.56), CD4/CD8 ratio (OR = 0.29; 95% CI = 0.09-0.93), and bioimpedance phase angle (OR = 0.22; 95% CI = 0.12-0.40) were associated with decreased likelihood of low muscle mass. Lastly, having less than eight years of education (OR = 1.87; 95% CI = 1.02-3.41) and being non-employed (OR = 8.18; 95% CI = 3.09-21.61) increased the chance of low chair stand performance. In addition, higher CD4 + lymphocytes count (OR = 0.99; 95% CI = 0.99-0.99) was associated with a decreased likelihood of low chair stand performance. In conclusion, specific and non-specific HIV-related factors are associated with low handgrip strength, low muscle mass, and/or low chair stand performance.

The interplay between physiotherapist and exercise physiologist in the exercise oncology program / A interação entre fisioterapeuta e o profissional de educação física no programa de exercício oncológico

ABSTRACT Exercise is a relevant tool in the oncology rehabilitation program due to restoring functional capacity, improving quality of life, and preventing early cancer mortality, mainly in unfit cancer patients. According to a systematic physical evaluation and risk stratification model, exercise physiologists (or equivalent) and physiotherapists with additional cancer exercise training are candidates to provide and supervise exercise to cancer survivors. However, the referral pathways are unclear, and a few cancer survivors are educated about personalized exercise oncology programs. This article aims to engage and stimulate additional training of Exercise physiologists and Physiotherapists in a collaborative exercise oncology program and proposes a dynamic and supervised model to attend to the emerging multidisciplinary scenario of cancer.

RESUMO Exercício físico é uma ferramenta fundamental no programa de reabilitação oncológica. Seu foco está em restaurar parâmetros físico-funcionais, melhorar a qualidade de vida e prevenir mortalidade precoce, especialmente em pacientes oncológicos mais fragilizados. Profissionais de educação física e fisioterapeutas com capacitação em oncologia são elegíveis em prescrever e supervisionar exercícios a esse público, seguindo um criterioso modelo de avaliação contínua e estratificação de risco. Contudo, o fluxo de direcionamento do paciente oncológico a esses profissionais não está estabelecido e poucos pacientes são beneficiados por um programa de exercícios personalizados no Brasil. Este artigo tem o objetivo de engajar e estimular a capacitação de profissionais de educação física e fisioterapeutas no programa de exercício oncológico e propor um modelo colaborativo de avaliação e supervisão de exercícios alinhado a um crescente cenário multidisciplinar do câncer.

Effect of a single resistance exercise session on inflammatory markers and oxidative stress in women living with HIV / Efeito de uma única sessão de exercício resistido sobre marcadores inflamatórios e estresse oxidativo em mulheres vivendo com hiv

ABSTRACT People living with HIV (PLH), who use antiretroviral therapy (ART), are more susceptible to changes in the inflammatory profile and oxidative stress, and women have greater access to ART. Although physical exercise is a complementary strategy to treatment due to its antioxidant and anti-inflammatory effects, it is not clear whether acute responses to exercise can be harmful to PLH. The aim of the study was to investigate the acute effect of resistance exercise (RE) on inflammatory and oxidative stress markers in PLH. Ten women, using ART, performed RE session consisting of seven exercises for the whole body. For biochemical evaluation, blood samples were collected before (pre), 1 hour (1h) and 2 hours (2h) after the RE session. One-way ANOVA followed by Bonferroni's post hoc test was used to compare results between time points. There was an increase only in markers, GSSG of 160% (pre: 0.40 ± 0.11; 1h: 1.18 ± 0.36; 2h: 1.04 ± 0.25 mmol/g), TNF-α of 98 % (pre: 4.60 ± 0.55; 1h: 6.95 ± 0.77; 2h: 9.10 ± 1.03 pg/ml) and 52% IL-6 (pre: 2.47 ± 0 .67; 1h: 3.63 ± 1.26; 2h: 5.38 ± 2.15 pg/ml). The other variables remained unchanged (P > 0.05). It is concluded that a RE session increased the levels of inflammatory markers and oxidative stress in PLH in a non-exacerbated way.

RESUMO Pessoas vivendo com HIV (PVH), que utilizam a terapia antirretroviral (TARV), são mais suscetíveis a alterações no perfil inflamatório e estresse oxidativo, sendo que as mulheres possuem maior acesso à TARV. Embora o exercício físico seja uma estratégia complementar ao tratamento devido aos seus efeitos antioxidantes e anti-inflamatórios, não está claro se as respostas agudas ao exercício podem ser prejudiciais às PVH. O objetivo do estudo foi investigar o efeito agudo de exercícios com pesos (EP) sobre marcadores inflamatórios e de estresse oxidativo em PVH. Dez mulheres, em uso da TARV, realizaram uma sessão de EP constituída por sete exercícios para o corpo todo. Para avaliação bioquímica, amostras de sangue foram coletadas antes (pré), 1 hora (1h) e 2 horas (2h) após a sessão de EP. A ANOVA one-way seguida do teste post hoc de Bonferroni foi utilizada para comparação dos resultados entre os momentos. Houve aumento apenas nos marcadores, GSSG de 160% (pré: 0,40 ± 0,11; 1h: 1,18 ± 0,36; 2h:1,04 ± 0,25 mmol/g), TNF-α de 98% (pré: 4,60 ± 0,55; 1h: 6,95 ± 0,77; 2h: 9,10 ± 1,03 pg/ml) e IL-6 de 52% (pré: 2,47 ± 0,67; 1h: 3,63 ± 1,26; 2h: 5,38 ± 2,15 pg/ml). As demais variáveis permaneceram sem alterações (P > 0,05). Conclui-se que uma sessão de EP aumentou os níveis de marcadores inflamatórios e estresse oxidativo em PVH de forma não exacerbada.

Creatine supplementation protects against diet-induced non-alcoholic fatty liver but exacerbates alcoholic fatty liver.

AIMS: This work investigated the effects of creatine supplementation on different pathways related to the pathogenesis of non-alcoholic fatty liver disease and alcoholic liver disease. MAIN METHODS: To induce alcoholic liver disease, male Swiss mice were divided into three groups: control, ethanol and ethanol supplemented with creatine. To induce non-alcoholic fatty liver disease, mice were divided into three groups: control, high-fat diet and high-fat diet supplemented with creatine. Each group consisted of eight animals. In both cases, creatine monohydrate was added to the diets (1 %; weight/vol). KEY FINDINGS: Creatine supplementation prevented high-fat diet-induced non-alcoholic fatty liver disease progression, demonstrated by attenuated liver fat accumulation and liver damage. On the other hand, when combined with ethanol, creatine supplementation up-regulated key genes related to ethanol metabolism, oxidative stress, inflammation and lipid synthesis, and exacerbated ethanol-induced liver steatosis and damage, demonstrated by increased liver fat accumulation and histopathological score, as well as elevated oxidative damage markers and inflammatory mediators. SIGNIFICANCE: Our results clearly demonstrated creatine supplementation exerts different outcomes in relation to non-alcoholic fatty liver disease and alcoholic liver disease, namely it protects against high-fat diet-induced non-alcoholic fatty liver disease but exacerbates ethanol-induced alcoholic liver disease. The exacerbating effects of the creatine and ethanol combination appear to be related to oxidative stress and inflammation-mediated up-regulation of ethanol metabolism.

Resistance Training Attenuates Activation of STAT3 and Muscle Atrophy in Tumor-Bearing Mice.

Purpose: Although the role of signal transducers and activators of transcription (STAT3) in cachexia due to the association of circulating IL-6 and muscle wasting has been extensively demonstrated, the effect of resistance training on STAT3 in mediating muscle atrophy in tumor-bearing mice is unknown. The aim of this study is to investigate the effects of resistance exercise training on inflammatory cytokines and oxidative-mediated STAT3 activation and muscle loss prevention in tumor-bearing mice. Methods: Male Swiss mice were inoculated with Ehrlich tumor cells and exposed or not exposed to resistance exercise protocol of ladder climbing. Skeletal muscle STAT3 protein content was measured, compared between groups, and tested for possible association with plasma interleukins and local oxidative stress markers. Components of the ubiquitin-proteasome and autophagy pathways were assessed by real-time PCR or immunoblotting. Results: Resistance training prevented STAT3 excessive activation in skeletal muscle mediated by the overabundance of plasma IL-6 and muscle oxidative stress. These mechanisms contributed to preventing the increased key genes and proteins of ubiquitin-proteasome and autophagy pathways in tumor-bearing mice, such as Atrogin-1, LC3B-II, and Beclin-1. Beyond preventing muscle atrophy, RT also prevented strength loss and impaired locomotor capacity, hallmarks of sarcopenia. Conclusion: Our results suggest that STAT3 inhibition is central in resistance exercise protective effects against cancer-induced muscle atrophy and strength loss.

Effect of running exercise on titanium dioxide (TiO2)-induced chronic arthritis and sarcopenia in mice. A titanium prosthesis loosening injury model study.

AIMS: This study aimed to investigate if titanium dioxide (TiO2) joint administration is a useful pre-clinical model to study sarcopenia-related chronic arthritis, and if exercise is a useful therapeutic approach against the pathogenesis of TiO2-induced arthritis and sarcopenia in mice. MAIN METHODS: Two experiments were conducted. Firstly, 36 female Swiss mice were randomly divided into a control group (n = 12) and two groups who received intra-articular TiO2 injections of 0.3-mg (n = 12) and 3-mg (n = 12), respectively. Mice were euthanized 4 and 8 weeks after TiO2 injections. Based on data of the first experiment, mice were exposed to four groups: control (C, n = 10), exercised (Ex, n = 10), injected with 3-mg of TiO2 (TiO2, n = 10), and injected with 3-mg of TiO2 and exercised (TiO2 + Ex, n = 10) for a total of 8-weeks. KEY FINDINGS: Eight-week of 3 mg of TiO2 joint administration promoted characteristics of chronic inflammation such as elevated histopathological score, inflammation, edema and pain. Hallmarks of sarcopenia were also observed such as muscle atrophy and loss of strength. Furthermore, voluntary exercise running reduced TiO2-induced chronic inflammation and pain, attenuating chronic arthritis-related muscle atrophy, strength loss and impairment of locomotion capacity. In addition, exercise was also able to prevent TiO2-induced collagen degradation, an important marker of functional and structural integrity loss of cartilage and chronic arthritis disease progression. SIGNIFICANCE: TiO2 joint administration mimed titanium prosthesis release-induced joint chronic arthritis and sarcopenia-related chronic arthritis, disturbances that were attenuated by voluntary exercise.

Costly immunometabolic remodelling in disused muscle buildup through physical exercise.

The mechanisms underlying the immunometabolic disturbances during skeletal muscle atrophy caused by a plethora of circumstances ranging from hospitalization to spaceflight missions remain unknown. Here, we outline the possible pathways that might be dysregulated in such conditions and assess the potential of physical exercise to mitigate and promote the recovery of muscle morphology, metabolism and function after intervals of disuse. Studies applying exercise to attenuate disuse-induced muscle atrophy have shown a pivotal role of circulating myokines in the activation of anabolic signalling pathways. These muscle-derived factors induce accretion of contractile proteins in the myofibers, and at the same time decrease protein breakdown and loss. Regular exercise plays a crucial role in re-establishing adequate immunometabolism and increasing the migration and presence in the muscle of macrophages with an anti-inflammatory phenotype (M2) and T regulatory cells (Tregs) after disease-induced muscle loss. Additionally, the switch in metabolic pathways (glycolysis to oxidative phosphorylation [OXPHOS]) is important for achieving rapid metabolic homeostasis during muscle regeneration. In this review, we discuss the molecular aspects of the immunometabolic response elicited by exercise during skeletal muscle regeneration. There is not, nevertheless, consensus on a single optimal intensity of exercise required to improve muscle strength, mass and functional capacity owing to the wide range of exercise protocols studied so far. Despite the absence of agreement on the specific strategy, physical exercise appears as a powerful complementary strategy to attenuate the harmful effects of muscle disuse in different scenarios.

Sarcopenia Related to Human Immunodeficiency Virus: Protective Effects of Exercise.

We discuss recent evidence supporting the hypothesis that sarcopenia is an emerging health concern among people with human immunodeficiency virus (HIV) because of increasing life expectancy and HIV- and treatment-related comorbidities. We also hypothesize that combined exercise at higher intensity has a key role in managing sarcopenia in this population because it directly (increases muscle strength and stimulates hypertrophy) and indirectly (prevents mitochondrial dysfunction, oxidative stress, and persistent inflammation) counteracts sarcopenia hallmarks.

Voluntary Exercise Attenuates Hyperhomocysteinemia, But Does not Protect Against Hyperhomocysteinemia-Induced Testicular and Epididymal Disturbances.

The hyperhomocysteinemia (HHcy) is toxic to the cells and associated with several diseases. Clinical studies have shown changes in plasma concentrations of Hcy after physical exercise. This study aimed to assess the effect of HHcy on testis, epididymis and sperm quality and to investigate whether voluntary exercise training protects this system against damage caused by HHcy in Swiss mice. In this study, 48 mice were randomly distributed in the control, HHcy, physical exercise, and HHcy combined with physical exercise groups. HHcy was induced by daily administration of dl-homocysteine thiolactone via gavage throughout the experimental period. Physical exercise was performed through voluntary running on the exercise wheels. The plasma concentrations of homocysteine (Hcy) and testosterone were determined. The testes and epididymis were used to assess the sperm count, histopathology, lipoperoxidation, cytokine levels, testicular cholesterol, myeloperoxidase, and catalase activity. Spermatozoa were analyzed for morphology, acrosome integrity, mitochondrial activity, and motility. In the testes, HHcy increased the number of abnormal seminiferous tubules, reduced the tubular diameter and the height of the germinal epithelium. In the epididymis, there was tissue remodeling in the head region. Ultimately, voluntary physical exercise training reduced plasma Hcy concentration but did not attenuate HHcy-induced testicular and epididymal disturbances.