Myogenic microRNAs as Therapeutic Targets for Skeletal Muscle Mass Wasting in Breast Cancer Models.

Breast cancer is the type of cancer with the highest prevalence in women worldwide. Skeletal muscle atrophy is an important prognostic factor in women diagnosed with breast cancer. This atrophy stems from disrupted skeletal muscle homeostasis, triggered by diminished anabolic signalling and heightened inflammatory conditions, culminating in an upregulation of skeletal muscle proteolysis gene expression. The importance of delving into research on modulators of skeletal muscle atrophy, such as microRNAs (miRNAs), which play a crucial role in regulating cellular signalling pathways involved in skeletal muscle protein synthesis and degradation, has been recognised. This holds true for conditions of homeostasis as well as pathologies like cancer. However, the determination of specific miRNAs that modulate skeletal muscle atrophy in breast cancer conditions has not yet been explored. In this narrative review, we aim to identify miRNAs that could directly or indirectly influence skeletal muscle atrophy in breast cancer models to gain an updated perspective on potential therapeutic targets that could be modulated through resistance exercise training, aiming to mitigate the loss of skeletal muscle mass in breast cancer patients.

Muscle Mass and Strength Gains Following Resistance Exercise Training in Older Adults 65-75 Years and Older Adults Above 85 Years.

Resistance exercise training (RET) can be applied effectively to increase muscle mass and function in older adults (65-75 years). However, it has been speculated that older adults above 85 years are less responsive to the benefits of RET. This study compares the impact of RET on muscle mass and function in healthy older adults 65-75 years versus older adults above 85 years. We subjected 17 healthy older adults 65-75 years (OLDER 65-75, n = 13/4 [female/male]; 68 ± 2 years; 26.9 ± 2.3 kg/m2) and 12 healthy older adults above 85 years (OLDER 85+, n = 7/5 [female/male]; 87 ± 3 years; 26.0 ± 3.6 kg/m2) to 12 weeks of whole-body RET (three times per week). Prior to, and after 6 and 12 weeks of training, quadriceps and lumbar spine vertebra 3 muscle cross-sectional area (computed tomography scan), whole-body lean mass (dual-energy X-ray absorptiometry scan), strength (one-repetition maximum test), and physical performance (timed up and go and short physical performance battery) were assessed. Twelve weeks of RET resulted in a 10% ± 4% and 11% ± 5% increase in quadriceps cross-sectional area (from 46.5 ± 10.7 to 51.1 ± 12.1 cm2, and from 38.9 ± 6.1 to 43.1 ± 8.0 cm2, respectively; p < .001; η2 = .67); a 2% ± 3% and 2% ± 3% increase in whole-body lean mass (p = .001; η2 = .22); and a 38% ± 20% and 46% ± 14% increase in one-repetition maximum leg extension strength (p < .001; η2 = .77) in the OLDER 65-75 and OLDER 85+ groups, respectively. No differences in the responses to RET were observed between groups (Time × Group, all p > .60; all η2 ≤ .012). Physical performance on the short physical performance battery and timed up and go improved (both p < .01; η2 ≥ .22), with no differences between groups (Time × Group, p > .015; η2 ≤ .07). Prolonged RET increases muscle mass, strength, and physical performance in the aging population, with no differences between 65-75 years and 85+ years older adults.

Effects of high-intensity interval training on lean mass, strength, and power of the lower limbs in healthy old and young people.

Introduction: Whether high-intensity interval training (HIIT) can improve lean mass, strength, and power of the lower limbs in young and older people is still under discussion. This study aimed to determine the effect of HIIT on lean mass, maximal strength, rate of force development (RFD), and muscle power of both lower limbs in healthy young and older adults. Secondarily, to compare the effects of HIIT between dominant vs. non-dominant lower limbs of each group. Materials and methods: Healthy older (n = 9; 66 ± 6 years; BMI 27.1 ± 3.1 kg m-2) and young (n = 9; 21 ± 1 years; BMI 26.2 ± 2.8 kg m-2) men underwent 12 weeks of HIIT (3x/week) on a stationary bicycle. The evaluations were made before and after the HIIT program by dual energy X-ray absorptiometry (DEXA), anthropometry, force transducer and, Sit-to-Stand test. The outcomes analyzed were limb lean mass, thigh circumference, maximal voluntary isometric strength, RFD (Time intervals: 0-50, 50-100, 100-200, and 0-200 ms), and muscle power in both lower limbs. Results: After 12 weeks of HIIT, non-dominant limb (NDL) showed increase in limb lean mass (p < 0.05) but without interaction (time*group). HIIT showed a gain in absolute maximal strength and also when adjusted for thigh circumference in the dominant lower limb (DL) in both groups. The RFD0-200 ms showed differences between groups but without interaction. The RFD0-50 ms of the NDL showed post-training improvements (p < 0.05) in both groups. Only the older group showed differences between DL vs. NDL in most of the RFD obtained post-intervention. In addition, post-HIIT muscle power gain was observed in both groups (p < 0.05), but mainly in older adults. Conclusion: HIIT promotes increases in lean mass, maximal strength, early RFD, and lower limb muscle power in healthy older and young individuals. The differences shown between the DL and the NDL must be analyzed in future studies.

High-intensity interval training reduces the induction of neutrophil extracellular traps in older men using live-neutrophil imaging as biosensor.

Neutrophil extracellular trap formation (NETosis) is a mechanism used by neutrophils to capture pathogens with their own DNA. However, the exacerbation of this immune response is related to serious inflammatory diseases. Aging is known to lead to an excessive increase in NETosis associated with various diseases. Under this scenario, the search for strategies that regulate the release of NETosis in older people becomes relevant. High-intensity interval training (HIIT) involves repeated bouts of relatively intense exercise with alternating short recovery periods. This training has shown beneficial effects on health parameters during aging and disease. However, little is known about the potential role of HIIT in the regulation of NETosis in healthy older people. The aim of this study was to evaluate the induction of NETosis by serum from healthy young and older men, before and after 12 weeks of HIIT using healthy neutrophils as a biosensor. HIIT was performed 3 times per week for 12 weeks in young (YOUNG; 21 ± 1 years, BMI 26.01 ± 2.64 kg⋅m-2, n = 10) and older men (OLDER; 66 ± 5 years, BMI 27.43 ± 3.11 kg⋅m-2, n = 10). Serum samples were taken before and after the HIIT program and NETosis was measured with live cell imaging in donated neutrophils cultured with serum from the participants for 30 h. Our results showed that serum from older men at baseline induced greater baseline NETosis than younger men (p < 0.05; effect size, ≥0.8), and 12 weeks of HIIT significantly reduced (Interaction Effect, p < 0.05; effect size, 0.134) the induction of NETosis in older men. In conclusion, HIIT is a feasible non-invasive training strategy modulating NETosis induction. Additionally, the use of neutrophils as a biosensor is an effective method for the quantification of NETosis induction in real time.

Characterization of muscle mass, strength and mobility of critically ill patients with SARS-CoV-2 pneumonia: Distribution by sex, age, days on mechanical ventilation, and muscle weakness.

Objective: Quantify and categorize by sex, age, and time spent on mechanical ventilation (MV), the decline in skeletal muscle mass, strength and mobility in critically ill patients infected with SARS-CoV-2 and requiring mechanical ventilation while at intensive care unit (ICU). Design: Prospective observational study including participants recruited between June 2020 and February 2021 at Hospital Clínico Herminda Martin (HCHM), Chillán, Chile. The thickness of the quadriceps muscle was evaluated by ultrasonography (US) at intensive care unit admission and awakening. Muscle strength and mobility were assessed, respectively, through the Medical Research Council Sum Score (MRC-SS) and the Functional Status Score for the Intensive Care Unit Scale (FSS-ICU) both at awakening and at ICU discharge. Results were categorized by sex (female or male), age (<60 years old or ≥60 years old) and time spent on MV (≤10 days or >10 days). Setting: Intensive care unit in a public hospital. Participants: 132 participants aged 18 years old or above (women n = 49, 60 ± 13 years; men n = 85, 59 ± 12 years) admitted to intensive care unit with a confirmed diagnosis of severe SARS-CoV-2 and requiring MV for more than 48 h were included in the study. Patients with previous physical and or cognitive disorders were excluded. Interventions: Not applicable. Results: Muscle thickness have significantly decreased during intensive care unit stay, vastus intermedius (-11%; p = 0.025), rectus femoris (-20%; p < 0.001) and total quadriceps (-16%; p < 0.001). Muscle strength and mobility were improved at intensive care unit discharge when compared with measurements at awakening in intensive care unit (time effect, p < 0.001). Patients ≥60 years old or on MV for >10 days presented greater muscle loss, alongside with lower muscle strength and mobility. Conclusion: Critically ill patients infected with SARS-CoV-2 and requiring MV presented decreased muscle mass, strength, and mobility during their intensive care unit stay. Factors associated with muscle mass, such as age >60 years and >10 days of MV, exacerbated the critical condition and impaired recovery.

Calidad de vida, nivel de actividad física y pruebas funcionales en personas adultas y mayores laboralmente activas / Quality of life, level of physical activity and functional tests in actively working adults and older people

BACKGROUND: The population of actively working older people is growing rapidly. The relationship between quality of life, levels of physical activity and functionality in this population is not entirely clear. AIM: To determine the association between quality of life, levels of physical activity and functional tests in actively working adults and older people. MATERIAL AND METHODS: Cross sectional assessment of 138 adults aged 40 to 50 years (53% women) and 119 older people aged 60 to 75 years (53% women) who were actively working in two public services. Quality of life was measured with the SF-36 questionnaire and usual physical activity was assessed with the International Physical Activity Questionnaire (IPAQ-short). Handgrip strength, the timed up and go (TUG) and chair stand test (CST) were used as functional tests. RESULTS: Compared to older people, adults had better physical functional tests (P < 0.01). Older people had better scores in the mental health component (MHC) of quality of life (p < 0.05). In adults, the physical health component of quality of life (CSF) had a positive association with physical activity (Spearman Rho (rs)= 0.270; p = 0.01), grip strength (rs = 0.330; p < 0.01) and the TUG (rs = −0.229; p < 0.01). In older patients, CSM and CST were positively correlated (rs = 0.201; P = 0.029). In both groups, a correlation was observed between CSM, grip strength (adults rs = 0.283; p < 0.01; older people rs = 0.211; P = 0.02) and with TUG (adults rs = −0.197; P = 0.021; older people rs = - 0.212; p = 0.02). CONCLUSIONS: There is a positive correlation between quality of life and level of physical activity in working adults, which is not observed in older people. Adequate performance in physical functional tests is positively correlated with better quality of life (CSF and CSM) in adults and only with the mental health component in older people.

Physical therapy protocols to attenuate skeletal muscle atrophy in critically ill patients: narrative review / Protocolos de terapia física para atenuar la atrofia del músculo esquelético en pacientes críticos: revisión narrativa

SUMMARY: To describe the physical therapy protocols used in critically ill patients to attenuate skeletal muscle atrophy. We conducted a search in PubMed and Embase from inception to November 2020. Observational or experimental studies published in English or Spanish that evaluated the effect of physical therapy protocols on the attenuation of skeletal muscle atrophy in critically ill patients through muscle strength or mass measurement were considered eligible. Studies were only included if they reported a detailed description of the dosing of the interventions. Seventeen studies met the eligibility criteria. We included randomised clinical trials (n = 16) and observational studies (n = 1). The total population of the included studies was 872 critically ill patients. The studies aimed to evaluate the reliability, safety or effectiveness of neuromuscular electrical stimulation (n = 10) protocols, early mobilisation (n = 3), ergometer training (n = 2), transfers in tilt table (n = 1), and blood flow restriction (n = 1). Physical therapy protocols are part of the critically ill patient's integral management. Strategies such as passive mobilisation, in-bed and out-of-bed transfers, gait training, ergometer training, and neuromuscular electrical stimulation substantially impact critically ill patients' prognoses and quality of life after hospital discharge.

RESUMEN: Describir los protocolos de terapia física usados en pacientes críticos para atenuar la atrofia muscular esquelética. Realizamos una búsqueda en PubMed y Embase desde el inicio hasta noviembre de 2020. Se consideraron los estudios observacionales o experimentales publicados en inglés o español que evaluaron el efecto de los protocolos de terapia física en la atenuación de la atrofia del músculo esquelético en pacientes críticos a través de la medición de la fuerza o la masa muscular. Los estudios solo se incluyeron si informaron una descripción detallada de la dosificación de las intervenciones. Diecisiete estudios cumplieron los criterios de elegibilidad. Se incluyeron ensayos clínicos aleatorizados (n = 16) y estudios observacionales (n = 1). La población total de los estudios incluidos fue de 872 pacientes en estado crítico. Los estudios tuvieron como objetivo evaluar la confiabilidad, seguridad o efectividad de los protocolos de estimulación eléctrica neuromuscular (n = 10), movilización temprana (n = 3), entrenamiento con ergómetro (n = 2), transferencias en mesa basculante (n = 1) y restricción del flujo sanguíneo (n = 1). Los protocolos de terapia física forman parte del manejo integral del paciente crítico. Es- trategias como la movilización pasiva, los traslados dentro y fuera de la cama, el entrenamiento de la marcha, el entrenamiento con ergómetro y la estimulación eléctrica neuromuscular tienen un impacto sustancial en el pronóstico y la calidad de vida de los pacientes críticos después del alta hospitalaria.

[Quality of life, level of physical activity and functional tests in actively working adults and older people]. / Calidad de vida, nivel de actividad física y pruebas funcionales en personas adultas y mayores laboralmente activas.

BACKGROUND: The population of actively working older people is growing rapidly. The relationship between quality of life, levels of physical activity and functionality in this population is not entirely clear. AIM: To determine the association between quality of life, levels of physical activity and functional tests in actively working adults and older people. MATERIAL AND METHODS: Cross sectional assessment of 138 adults aged 40 to 50 years (53% women) and 119 older people aged 60 to 75 years (53% women) who were actively working in two public services. Quality of life was measured with the SF-36 questionnaire and usual physical activity was assessed with the International Physical Activity Questionnaire (IPAQ-short). Handgrip strength, the timed up and go (TUG) and chair stand test (CST) were used as functional tests. RESULTS: Compared to older people, adults had better physical functional tests (P < 0.01). Older people had better scores in the mental health component (MHC) of quality of life (p < 0.05). In adults, the physical health component of quality of life (CSF) had a positive association with physical activity (Spearman Rho (rs)= 0.270; p = 0.01), grip strength (rs = 0.330; p < 0.01) and the TUG (rs = -0.229; p < 0.01). In older patients, CSM and CST were positively correlated (rs = 0.201; P = 0.029). In both groups, a correlation was observed between CSM, grip strength (adults rs = 0.283; p < 0.01; older people rs = 0.211; P = 0.02) and with TUG (adults rs = -0.197; P = 0.021; older people rs = - 0.212; p = 0.02). CONCLUSIONS: There is a positive correlation between quality of life and level of physical activity in working adults, which is not observed in older people. Adequate performance in physical functional tests is positively correlated with better quality of life (CSF and CSM) in adults and only with the mental health component in older people.

Anthropometric parameters, lower limb functionality and quality of life after high-intensity interval training in healthy young people versus older adults / Parámetros antropométricos, funcionalidad de miembros inferiores y calidad de vida posterior al entrenamiento interválico de alta intensidad en jóvenes versus personas mayores

SUMMARY: The aim of this study was to determine the effects of High-intensity interval training (HIIT) on the quality of life in healthy young people (YNG) and older adults (OLD)and its correlation with physical health status (anthropometric parameters and lower limb functionality) YNG (21 ? 2 years, BMI 26.37 ? 2.69 n = 12) and OLD (67 ? 5 years, BMI 27.16 ? 3.04 n = 12) groups underwent 12weeks of HIIT. Before and after the HIIT, anthropometric assessments, lower limb functionality tests, and SF-36 quality-of-life questionnaire were performed. There were no significant changes in the SF-36 dimensions (P>0.05). After HIIT, there were improvement percentage changes in Mental Component Summary (MCS) (YNG, +8.51 ? 25.80 % vs. OLD, +2.30 ? 9.05 %) and in Physical Component Summary (PCS) (YNG, +2.66 ? 20.54 % vs. OLD, +4.34 ? 22.71 %). Negative correlations were observed between body mass index (BMI) with PCS (R=-0.570, P=0.009) and with MCS (R=-0.649, P=0.002) in OLD as well as between MCS and waist circumference (R=-0.557, P?0.001) in both groups. Also, correlations were observed between PCS and the sit-to-stand test (R=-0.424, P=0.006) in both groups and gait speed (R=0.458, P=0.042) only in YNG. HIIT promotes positive percentage changes in quality of life, with YNG showing better results in PCS and OLD in MCS. Quality of life and physical health status were correlated in both groups.

RESUMEN: Determinar los efectos del entrenamiento interválico de alta intensidad (HIIT) sobre la calidad de vida en jóvenes sanos (YNG) y personas mayores (OLD) y su correlación con el estado de salud física (parámetros antropométricos y funcionalidad de miembros inferiores). Ambos grupos, YNG (21 ? 2 años, IMC 26,37 ? 2,69 n = 12) y OLD (67 ? 5 años, IMC 27,16 ? 3,04 n = 12) realizaron 12 semanas de HIIT. Antes y después del HIIT, se realizaron evaluaciones antropométricas, pruebas de funcionalidad de miembros inferiores y cuestionario de calidad de vida SF-36. No hubo cambios significativos en las dimensiones del SF-36 (P >0,05). Después del HIIT, hubo cambios porcentuales de mejora en el componente sumario mental (MCS) (YNG, +8.51 ? 25.80 % vs. OLD, +2.30 ? 9.05 %) y el componente sumario física (PCS) (YNG, +2,66 ? 20,54 % vs. OLD, +2,30 ? 9,05 %), correspondientes a la calidad de vida. Se observaron correlaciones negativas entre el índice de masa corporal (IMC) con PCS (R=-0,570; P=0,009) y con MCS (R=0,649; P=0,002) en OLD, así como entre MCS y circunferencia de cintura (R = - 0,557, P?0,001) en ambos grupos. Además, se observaron correlaciones entre PCS y la prueba de sentarse y levantarse (R = -0,424; P = 0,006) en ambos grupos y la velocidad de la marcha (R = 0,458; P = 0,042) solo en YNG. HIIT promueve cambios porcentuales positivos en la calidad de vida, con YNG mostrando mejores resultados en PCS y OLD en MCS. La calidad de vida y el estado de salud física se correlacionaron en ambos grupos.

High-intensity interval training on body composition, functional capacity and biochemical markers in healthy young versus older people.

BACKGROUND: The aim of the following study was to identify the effects of a 12-week high-intensity interval training (HIIT) program on the modification of parameters of body composition, functional capacity as well as lipid and glucose homeostasis markers in healthy young people versus older adults. DESIGN: Experimental trial. METHODS: Healthy young (YNG, 21 ± 1 years, BMI 26.01 ± 2.64 kg·m-2, n = 10) and older (OLD, 66 ± 5 years, BMI 27.43 ± 3.11 kg·m-2, n = 10) males were subjected to 12 weeks of HIIT. Prior to and immediately after the HIIT program, dual-energy X-ray absorptiometry, dominant leg strength one-repetition maximum (1-RM), maximal oxygen uptake (VO2max) and physical performance tests were performed. Blood samples were also taken. RESULTS: Flexibility (P = 0.000), static balance (P = 0.004), timed up and go test (TUG) (P = 0.015), short physical performance battery (SPPB) (P = 0.005), dominant leg strength 1-RM (P = 0.012), and VO2max (P = 0.000) were better in YNG versus OLD. HIIT improved the % whole-body fat mass (P = 0.031), leg lean mass (P = 0.047), dominant leg strength 1-RM (P = 0.025), VO2max (P = 0.000), fasting cholesterol (P = 0.017) and fasting glucose (P = 0.006). TUG was improved by the training only in the OLD group (P = 0.016), but insulin (P = 0.002) and the homeostasis model assessment - insulin sensitivity (HOMA-IS) (P = 0.000) decreased only in the YNG group. HOMA-IS was correlated positive with BMI (R = 0.474, P = 0.035) and with whole-body fat mass (R = 0.517, P = 0.019). CONCLUSIONS: HIIT for 12 weeks improves parameters of body composition, functional capacity and fasting serum lipid and glucose homeostasis markers in healthy young and older participants. Young people are shown as benefiting more.

Skeletal Muscle Aging Atrophy: Assessment and Exercise-Based Treatment.

In the ordinary course of aging, individuals change their body composition, mainly reducing their skeletal muscle mass and increasing their fat mass. In association, muscle strength and functionality also decrease. The geriatric assessment allows knowing the baseline situation of the patients, determines the impact of diseases, and defines specific treatments. There are various tools to evaluate the health condition of older people. These tools include the assessment scales of necessary Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL), physical and functional assessment scales, and instruments that assess the cognitive state of the person. There are several strategies that have been proposed to combat skeletal muscle atrophy due to aging, such as physical exercise, nutritional supplements, or drugs. Some researchers have highlighted the efficacy of the combination of the mentioned strategies. In this chapter, we will focus only on physical exercise as a strategy to reduce skeletal muscle loss during aging.