Cachexia occurs commonly and is a significant cause of morbidity and up to 20% mortality in patients with cancer. Loss of muscle mass occurs as part of the cachexia wasting process and low muscle mass is a key element of the most recent consensus cachexia definition. Measuring muscle mass and changes in skeletal muscle is important to phenotype cachectic individuals and to monitor response to anti-cachectic treatments. This thesis investigates minimally invasive or burdensome methods of measuring muscle mass and muscle protein kinetics for use in a clinical or research setting. Quantification of muscle area on routine diagnostic cross-sectional imaging offers a novel and relatively non-invasive method of assessing both regional (and by extrapolation) whole body muscle mass. The need for such a direct measurement of muscle mass was demonstrated by showing that simple anthropometric formulae are unable to predict muscularity accurately (within 25%) when compared with estimates derived from patients diagnostic CT scans. It may be that qualitative changes in muscle may be more sensitive indices of the wasting process rather than qualitative change. Myosteatosis (infiltration of muscle by fat) is known to occur in both cachexia and age related sarcopenia and can be quantified using the Hounsfield spectrum observed on routine diagnostic CT scans. However, not all patients undergo routine CT scanning and there is a need for a biomarker derived from urine or blood. Consequently, cross sectional imaging was used to phenotype patients in a proteomic analysis of urine with the aim of identifying protein or peptide biomarkers associated with myosteatosis in cancer cachexia. A biomarker model for myosteatosis was developed with good sensitivity (97%) but poor specificity (71%). Many of the potential protein / peptide markers identified had poor associations with known mechanisms of muscle wasting and further study of the identified peptides in an extended cohort would help determine the validity of the present findings. However, two proteins with potential roles in muscle repair or neuromuscular function (Agarin and Cathepsin C) were identified and these may warrant targeted investigation with evaluation against sequential measures of muscle mass to determine their value in defining muscle loss over time. As different regional measures of muscularity are available, trunk (L3 CT) and limb muscle (quadriceps MRI) cross sectional measurements were compared with functional assessments to determine the optimal site for measurement. Neither measure proved superior to the other but appeared to reflect different aspects of function. Quadriceps muscle area correlated with quadriceps strength and power whilst truncal muscle area correlated more with complex movements such as the timed-up-and-go test. Changes in regional muscle area in patients with upper gastrointestinal cancer were assessed by upper and lower limb MRI before and after surgery and by L3 CT cross sectional area before and after neo-adjuvant chemotherapy. No change in limb muscularity was seen at 220 days post operatively compared with pre-op measurements. During neo-adjuvant chemotherapy a significant loss of truncal muscle occurred in the absence of significant weight loss suggesting that sequential cross sectional imaging is capable of detecting changes in body composition that may not be apparent clinically. Whilst sequential scans may document changes in muscularity, they do not describe the underlying levels of muscle synthesis or degradation that may regulate muscle volume. The final section of this thesis describes the development of a novel tracer method to measure skeletal muscle synthesis and its application in a study of patients with cancer and healthy volunteers. This novel method was able to measure skeletal muscle fractional synthetic rate (FSR) over a longer time-period than previous methods (weeks rather than hours) and reduced the burden on the patient by the use of a single oral tracer dose and single muscle biopsy. Comparison of synthesis rates in quadriceps and rectus abdominis showed higher rates in quadriceps, 0.067% per hour vs 0.058% per hour respectively. Despite a net loss of muscle as measured by serial CT scans, skeletal muscle FSR appeared to be marginally increased in weight losing patients with cancer compared with weight stable patients and healthy controls. When FSR was combined with measures of muscle mass it was demonstrated that only small differences between synthesis and degradation are required to see the levels of muscle wasting seen in patients with cancer. In summary, routine cross sectional imaging provides a useful and unique measure of muscularity that is associated with function in patients with cancer Sequential scans can provide additional information about changes in body composition even in the absence of weight loss. There are significant regional variations in both muscle wasting and skeletal muscle fractional synthetic rate. The combination of sequential estimates of muscle mass from diagnostic CT scans along with estimates of FSR allow assessment of the contribution of altered synthesis and degradation to muscle loss. In patients with upper GI cancer it would appear that increased degradation may be more important that altered synthesis. The relative change in either process to account for absolute loss of muscle mass is small. Such findings have implications for the targeted therapy of muscle wasting in cancer patients.

We are grateful to Centro de Investigacion del Envejecimiento (CIEN) of Universidad San Martin de Porres (USMP) for providing us with the database for the study. To the faculty team of research of the medical school of Universidad de Ciencias Aplicadas (UPC) for their appreciations and comments. Jorge L. Maguiña is a doctoral candidate studying Epidemiological Research at Universidad Peruana Cayetano Heredia under FONDECYT/CIENCIACTIVA scholarship EF033-235-2015 and supported by training grant D43 TW007393 awarded by the Fogarty International Center of the US National Institutes of Health . / El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Introduction: Sarcopenia is a geriatric syndrome characterized by loss of muscle mass and strength. The prevalence in people between 60–70 years is about 5–13% and in adults over 80 years, between 11–50% in the USA. Sarcopenia increases the risk of mortality and nosocomial infections. Community-acquired pneumonia is the first infectious-related cause of death in elderly people. However, there is lack of evidence about the association between sarcopenia and pneumonia. The aim of our study was to determine the incidence and risk factors of community-acquired pneumonia in older adults with sarcopenia in a Peruvian hospital. Methods: A retrospective cohort study was conducted in the geriatrics service of Centro Medico Naval “Cirujano Mayor Santiago Tavara”. Sarcopenia was defined by “European Consensus of Sarcopenia” criteria. MultivariatePoisson regression model was conducted to estimate the effect of the independent association between sarcopenia and pneumonia. Results: A total of 1598 subjects were enrolled, 59.0% were male; with a mean age of 78.3 ± 8.6 years. The prevalence of sarcopenia was 15.1% (95% CI: 13.3–16.8) and the incidence of community-acquired pneumonia was 15.14% (95%CI 13.4–16.9). In the multivariate model, we found a higher incidence of pneumonia in sarcopenic compared to non-sarcopenic, RR(a) 3.88 (95% CI: 2.82–5.33). Discussion: Our study showed a higher incidence of community-acquired pneumonia in sarcopenic subject. Results provide information on the importance of detecting this syndrome because it gives us scientific evidence of the interest of a correct comprehensive geriatric assessment in older patients with a high risk of pneumonia. / We are grateful to Centro de Investigacion del Envejecimiento (CIEN) of Universidad San Martin de Porres (USMP) for providing us with the database for the study. To the faculty team of research of the medical school of Universidad de Ciencias Aplicadas (UPC) for their appreciations and comments. Jorge L. Maguiña is a doctoral candidate studying Epidemiological Research at Universidad Peruana Cayetano Heredia under FONDECYT/CIENCIACTIVA scholarship EF033-235-2015 and supported by training grant D43 TW007393 awarded by the Fogarty International Center of the US National Institutes of Health . / Revisión por pares / Revisión por pares

Objetivo General: Revisar sistemáticamente, la literatura científica indizada en las principales bases de datos de ciencias de la salud, en tomo a las actividades o programas de salud aplicados en personas mayores de 65 años. Material y Método: Estudio descriptivo transversal de los trabajos recuperados en la revisión bibliográfica mediante técnica sistemática. Se estudiaron ensayos clínicos aleatorizados publicados en revistas indizadas en bases de datos internacionales sujetas a revisión por pares y cuyo texto completo pudo ser recuperado. Las bases de datos consultadas fueron: MEDLINE, EMBASE, ISI, CINAHL, COCHRANE y LILACS. En la búsqueda se emplearon descriptores del Thesaurus de la Medical Subject Headings (MeSH), que fueron utilizados como Major Topic en las bases que lo permitieron. Las ecuaciones de búsqueda se limitaron a humanos y a personas mayores de 65 años, fueron desarrolladas en la base de datos MEDLINE, vía PubMed, usando conectores booleanos y adaptándose posteriormente a las otras bases de datos anteriormente mencionadas. Resultados: Las modalidades terapéuticas que han sido utilizadas para la promoción, mantenimiento o restauración de la salud física de las personas mayores de 65 años, se ven reflejadas en los 27 ensayos clínicos aleatorizados que fueron seleccionados y revisados. De los cuales surgen los 3 artículos científicos que forman el cuerpo principal de esta tesis y que han sido previamente publicados. En términos bibliométricos, dichos artículos presentaron una obsolescencia promedio de 6,33 años y un índice de Price de 40%. Conclusiones: - La implantación de programas de promoción en salud dirigidos a la población mayor que tienen en cuenta la condición de salud, han demostrado ser eficaces para fomentar cambios en el estilo de vida y producir una mejoría tanto en la condición física de los ancianos, como en el mantenimiento de su autonomía; repercutiendo así sobre su calidad de vida. - Para mejorar la eficacia de los programas, deberían realizarse por un tiempo mínimo de un año. - El entrenamiento con ejercicio excéntrico en personas mayores es una opción, para la disminución y prevención de la pérdida de estructura muscular y su consecuente disminución de fuerza y discapacidad. - Combinar el suplemento con ejercicio físico, refuerza los efectos que independientemente, cada una de estas intervenciones puede tener sobre la mejora de la masa y fuerza muscular, el balance y la velocidad, contribuyendo a la prevención de la sarcopenia y prolongando la independencia y autonomía de las personas mayores de 65 años.

Myostatin, a TGF-β superfamily member, is a key negative regulator of embryonic and postnatal muscle growth. In order to further elucidate the role of myostatin during postnatal growth, several lines of investigation were undertaken in mice. Analysis of myostatin downstream target genes identified several known and unknown genes. From these, the regulation of an androgen receptor binding co-factor, ARA70, was selected for further investigation. Reverse Northern analysis on the differentially expressed cDNA library indicated an increased expression of ARA70 in myostatin-null muscles, which was later confirmed by Northern blot and semi-quantitative PCR analysis. In corroboration, treatment of myoblast cultures with exogenous myostatin resulted in the down-regulation of ARA70, confirming that myostatin is a negative regulator of ARA70 gene expression. The role of myostatin during sarcopenia, a progressive age-related loss of skeletal muscle mass and strength, was also investigated. The atrophy associated with sarcopenia is frequently correlated with insufficient muscle regeneration, resulting from an impaired propensity of satellite cells to activate and a subsequent decline in myogenesis. Myostatin is a known inhibitor of postnatal satellite cell activation and muscle regeneration, thus muscle mass and regeneration, and satellite cell behaviour were examined in young and aged myostatin-null mice. Myostatin-null mice had increased individual muscle weights, as a consequence of massive fibre hypertrophy and hyperplasia, and an increased proportion of type IIB fibres. Aging induced oxidative fibre type changes and atrophy in the wild-type muscle while no fibre type switching was observed in the myostatin-null muscle and atrophy was minimal. No decrease in satellite cell numbers was observed with aging in both genotypes; though a gradual decline in the number of activated satellite cells was noted during aging. However, both young and aged myostatin-null mice displayed increased satellite cells and activation compared to wild-type mice, suggesting a greater myogenic potential in the myostatin-null satellite cells. Consistent with this, aged myostatin-null myoblasts proliferated faster and displayed a higher fusion index during differentiation than the aged wild-type myoblasts, confirming that the reduced sarcopenia in the myostatin-null mice was due to a preserved increase in the myoblast myogenic activity. An increase in a Pax7-only myoblast population from myostatin-null muscle indicated an enhanced satellite cell self-renewal process, consistent with the increased satellite cell number observed on the myostatin-null muscle fibres. Additionally, muscle regeneration of aged myostatin-null muscle following notexin injury was accelerated, and fibre hypertrophy and type were recovered with regeneration, unlike the aged wild-type muscle. Testing the therapeutic value of a myostatin antagonist, Mstn-ant1, indicated that a short term blockade of myostatin by the antagonist significantly enhanced muscle regeneration in aged mice after injury and during sarcopenia. Antagonism of myostatin led to satellite cell activation, increased Pax7 and MyoD protein levels, and greater myoblast and macrophage cell migration culminating in enhanced muscle regeneration in the aged mice. In conclusion, the hypertrophic phenotype associated with myostatin-null mice may in part result from increased androgen receptor (AR) activity due to the up-regulation of ARA70, given that increased expression of the AR leads to hypertrophy. Additionally, the increased muscle mass in myostatin-null mice is likely to result from an augmented myogenic potential and self-renewal process. Overall, a prolonged absence of myostatin reduced sarcopenia and the associated loss of muscle regenerative capacity. Furthermore, the antagonism of myostatin displayed significant therapeutic potential in the alleviation of sarcopenia, through the restoration of the myogenic and inflammatory responses in the aged environment. Thus, the research work clearly demonstrates the role of myostatin in sarcopenia, and documents for the first time a valid therapeutic for alleviating sarcopenia.

No description available.

Introduction: Chronic inflammation with aging is associated with sarcopenia and osteoporosis. Bovine colostrum is the first milk secreted by cows following parturition and contains bioactive substances, while ibuprofen is a non-steroidal anti-inflammatory drug. Both target the inflammatory pathway regulated by cyclooxygenase and have potential to increase muscle and bone mass when combined with resistance training. Objectives: To determine efficacy of novel anti-inflammatory nutritional (bovine colostrum) and pharmaceutical (ibuprofen) supplementation during resistance training on muscle and bone properties and strength in older adults. Methods: Older adults (≥50y) were randomly assigned to receive 38g/d of colostrum or whey protein during a resistance training program for 8 weeks; postmenopausal women (≥60y) were randomly assigned to receive ibuprofen (400 mg) or placebo post-exercise while performing a resistance training program or stretching program (3d/wk) for 9 months. Both studies utilized dual energy x-ray absorptiometry (DXA) for body composition and predicted 1-repetition maximum for strength. The bovine colostrum study further assessed muscle thickness of the biceps and quadriceps, plasma insulin-like growth factor-1, and inflammation and bone resorption markers; the ibuprofen study further assessed bone and muscle properties and estimates of bone strength (peripheral quantitative computed tomography), and dynamic balance. Results: Bovine colostrum supplementation during resistance training increased leg press strength (21%) and reduced bone resorption (-29%) versus whey protein. Both colostrum and whey protein groups improved chest press strength, muscle thickness, and lean tissue mass. Ibuprofen alone appeared beneficial for preventing loss of areal bone density at Ward’s region (3%) and bone properties at the distal radius (0.5%) and radial shaft (1.1%), while exercise alone appeared beneficial for bone properties at the distal radius (0.6%). However, the interaction of resistance training and ibuprofen negated the benefits at the distal radius (-1.5%). Neither ibuprofen nor resistance training was effective for increasing lean tissue mass, although resistance training improved body fat percentage (-2.0%), increased upper and lower body strength (23%, 110%), and preserved muscle density of the calf (-3.1%). Conclusion: While bovine colostrum could be taken within close proximity to exercise, ibuprofen should not be as it may interfere with the effects of exercise when the two interventions are combined.

Orientador: Henrique Luiz Monteiro / Banca: Luis Cuadrado Martin / Banca: Pasqual Barretti / Banca: Denise Rodrigues Bueno / Banca: Silvia Regina Barrile / Resumo: Objetivos: a) revisar o efeito do exercício resistido realizado durante a sessão de hemodiálise por meio de uma revisão sistemática e meta-análise, b) estimar a prevalência de sarcopenia por sexo e faixa etária em uma amostra de pacientes em hemodiálise por meio de diferentes critérios diagnósticos de massa muscular apendicular e força de preensão palmar (FPP) e analisar a concordância entre eles, e c) analisar o efeito de um protocolo de exercício resistido progressivo (ERP) contínuo intradialítico na composição corporal, função física e qualidade de vida (QV) de pacientes em hemodiálise. Métodos: para isso foram conduzidos três estudos principais. a) Uma revisão sistemática e meta-análise de estudos controlados e randomizados utilizando o treinamento resistido versus grupo controle em pacientes com doença renal crônica em hemodiálise foram realizadas. Foram pesquisadas cinco bases de dados eletrônicas (MEDLINE, EMBASE, SPORTDiscus, PEDro e The Cochrane Library) e o desfecho primário analisado foi a composição corporal e os desfechos secundários foram força muscular, capacidade funcional e qualidade de vida. As escala PEDro e GRADE avaliaram a análise de viés e qualidade das evidencias, respectivamente. b) No segundo estudo foi analisada a prevalência de sarcopenia em uma amostra de pacientes em hemodiálise, a partir de diferentes pontos de corte utilizados em estudos prévios. A sarcopenia foi diagnosticada a partir do baixo índice de massa magra apendicular e baixa FPP. A c... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Objectives: a) to review the effect of resistive training performed during the hemodialysis session through a systematic review and meta-analysis; b) to estimate the prevalence of sarcopenia by sex and age in a sample of patients on hemodialysis using different cut-points and to analyze the agreement between them; and c) to analyze the effect of a progressive resistance training (PRT) protocol on body composition, physical function and quality of life (QoL) of patients on hemodialysis. Methods: Three main studies were conducted. a) A systematic review and metaanalysis of randomised controlled trials using resistance training versus control group in people with chronic kidney disease undergoing haemodialysis treatment were conducted. Five electronic databases (MEDLINE, EMBASE, SPORTDiscus, PEDro and The Cochrane Library) were searched. The primary outcome was muscle mass and the secondary outcomes were muscle strength, functional capacity and QoL. The PEDro and GRADE scales evaluated the bias analysis and quality of the evidence, respectively. b) In the second study, the prevalence of sarcopenia in a sample of patients undergoing haemodialysis, using different cut-off points from previous studies was analyzed. Additionally the agreement between the cut-offs was performed by kappa index (κ). Sarcopenia was evaluated using appendicular lean mass index and handgrip strength (HGS). c) Finally, a randomized controlled clinical trial verified the effect of 12-week of an intradialytic PRT protocol on body composition assessed by dual energy X-ray absorptiometry (DEXA), in physical capacity assessed by HGS, sit-to-stand test (30-second) (STT), 6-minute walk test (6MWT) and sit-and-reach test (flexibility) and in the QoL using the Medical Outcomes Study Short-Form 36 questionnaire (SF-36) from hemodialysis patients. Results: the meta-analysis showed that resistance ... (Complete abstract electronic access below) / Doutor

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Departamento de Nutrição, Programa de Pós-Graduação em Nutrição Humana, 2017. / Texto parcialmente liberado pelo autor. Conteúdo restrito: Capítulo 5. Resultados, Apêndice A, Anexos A,B,C e D. / Submitted by Raquel Almeida (raquel.df13@gmail.com) on 2017-11-07T19:52:07Z No. of bitstreams: 1 2017_RobertaBorgesSilva_PARCIAL.pdf: 745465 bytes, checksum: e63147582f96788175314ed4ebdf6d7a (MD5) / Approved for entry into archive by Patrícia Nunes da Silva (patricia@bce.unb.br) on 2018-06-04T13:43:26Z (GMT) No. of bitstreams: 1 2017_RobertaBorgesSilva_PARCIAL.pdf: 745465 bytes, checksum: e63147582f96788175314ed4ebdf6d7a (MD5) / Made available in DSpace on 2018-06-04T13:43:26Z (GMT). No. of bitstreams: 1 2017_RobertaBorgesSilva_PARCIAL.pdf: 745465 bytes, checksum: e63147582f96788175314ed4ebdf6d7a (MD5) / CAPES / Introdução: sabe-se que o envelhecimento populacional, o qual é acelerado principalmente em países em desenvolvimento contribui para a ocorrência de condições crônicas e desfechos músculo-funcionais como a fragilidade, a incapacidade funcional e a sarcopenia. Estratégias nutricionais baseadas em padrões alimentares, como a dieta mediterrânea, podem agir como fatores de proteção contra estes desfechos. Objetivo: avaliar a associação entre adesão à dieta mediterrânea e fragilidade, incapacidade funcional e sarcopenia em idosos não institucionalizados, por meio de revisão sistemática da literatura com meta-análise. Métodos: foi feita busca nas principais bases de dados indexadas (MEDLINE, EMBASE, e outras) e literatura cinzenta por estudos que avaliaram a associação entre a adesão à dieta mediterrânea e fragilidade, incapacidade funcional e sarcopenia em idosos não institucionalizados com idade ≥ 60 anos. A seleção dos estudos, extração dos dados, e avaliação da qualidade metodológica dos estudos foi feita de forma independente por dois pesquisadores. Foram feitas meta-análises de efeitos randômicos com medidas de associação OR e seus respectivos intervalos de confiança (IC 95%). Resultados : Foram identificados 1666 artigos na busca nas bases de dados. Após retirada de duplicatas, rastreamento e avaliação da elegibilidade, 11 estudos foram incluídos na revisão. Um total de 19.958 indivíduos foram avaliados. Maior adesão à dieta Mediterrânea está associada negativamente com menor risco para fragilidade (OR 0,46, 95% IC: 0,26-0,81, I2=41,4%, p=0,18) e incapacidade funcional (OR 0,75, 95% IC: 0,61-0,93, I2=0,0%, p=0,78). Não foi possível calcular medida sumária para sarcopenia. Dados de uma coorte indicam que não há associação entre maior adesão à dieta Mediterrânea e sarcopenia; entretanto, resultados de um estudo transversal incluído na revisão mostram que esta associação existe. Conclusões : Maior adesão à dieta Mediterrânea tem efeito protetor contra fragilidade e incapacidade funcional, mas não sarcopenia. Mais estudos longitudinais são necessários para esclarecer a relação entre dieta Mediterrânea e sarcopenia. / Background: Population ageing is increasing, and this process and its characteristics influences on prevalence and incidence of chronic conditions and musculoskeletal-functional outcomes, such as frailty, functional disability and sarcopenia. Nutritional strategies focused on dietary patterns, such as the Mediterranean diet can be protective from these outcomes. Objective: The aim of this study was to investigate the association between adherence to Mediterranean diet and frailty, functional disability and sarcopenia in community-dwelling older people. Methods: We systematically reviewed indexed electronic databases (MEDLINE, EMBASE, and others) and grey literature for articles investigating the relationship between adherence to Mediterranean diet and frailty, functional disability and sarcopenia in community-dwelling older people aged 60 and over. Studies selection, quality of studies assessment and data extraction were held independently by two researchers. Random effects meta-analyses were performed and pooled ORs were obtained. Results: After search, screening and eligibility investigation, we included 11 studies, with a total of 19,958 subjects. A higher adherence to Mediterranean diet is negatively associated with frailty (OR 0.46, 95% CI: 0.26-0.81, I2=41.4%, p=0.18) and functional disability (OR 0.75, 95% CI: 0.61-0.93, I2=0.0%, p=0.78). We could not perform meta-analysis for sarcopenia. Cohort data indicates no association between adherence to Mediterranean diet and sarcopenia; however, cross-sectional results show a positive relationship. Conclusion: Mediterranean diet is protective of frailty and functional disability, but not sarcopenia. More longitudinal studies are needed to understand the relationship between Mediterranean diet and sarcopenia.

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Educação Física, Programa de Pós-Graduação em Educação Física, 2016. / Submitted by Fernanda Percia França (fernandafranca@bce.unb.br) on 2016-12-08T17:19:29Z No. of bitstreams: 1 2016_MarciaMendesCarvalho.pdf: 981579 bytes, checksum: eb5d2bef592b64f0e5bbb9f7ad882777 (MD5) / Approved for entry into archive by Raquel Viana(raquelviana@bce.unb.br) on 2017-01-09T20:23:41Z (GMT) No. of bitstreams: 1 2016_MarciaMendesCarvalho.pdf: 981579 bytes, checksum: eb5d2bef592b64f0e5bbb9f7ad882777 (MD5) / Made available in DSpace on 2017-01-09T20:23:41Z (GMT). No. of bitstreams: 1 2016_MarciaMendesCarvalho.pdf: 981579 bytes, checksum: eb5d2bef592b64f0e5bbb9f7ad882777 (MD5) / A sarcopenia é um processo multifatorial caracterizado pela perda da força e de massa do músculo esquelético, o que leva à redução da área de secção transversa (AST) muscular. O treinamento resistido (TR) é uma ferramenta importante para reduzir a sarcopenia, porém, a análise proteômica do músculo de ratos velhos após TR ainda é pouco estudado. O objetivo do presente estudo foi analisar o perfil proteômico de ratos velhos após o TR. Vinte e quatro Rattus norvegicus com 3 meses (298,74 ± 32,32g) e 21 meses (517,83 ± 76,30g) de idade foram divididos em grupo sedentários jovens (SJ, n = 6), treinados jovens (TJ, n = 6), sedentários velhos (SV, n = 6) e treinados velhos (TV, n = 6). Foram realizados 12 semanas de treinamento resistido, que consistiam em subir uma escada vertical (1,1 m, 0,18 m, 2 cm entre as grades e 80° de inclinação) com uma carga fixada na cauda do animal. O tamanho da escada induzia os animais a realizar de 8 a 12 movimentos por subida e foi realizado três vezes por semana (segundas, quartas e sextas-feiras) durante 12 semanas. As cargas eram definidas de acordo com a capacidade de carregamento dos animais e aumentadas progressivamente com 65, 85, 95 e 100% da capacidade de carga máxima de carregamento de cada animal. Após a última sessão de treino, o músculo gastrocnêmio foi extraído e os compostos proteicos foram analisados por cromatografia líquida acoplada a uma fonte de ionização por Electrospray tandem Espectrometria de Massas (LC-ESI-MS/MS). As amostras foram identificadas utilizando banco de dados UniProt / Swissprot. As proteínas foram consideradas reguladas, quando o escore dos peptídeos esteve maior que o escore mínimo para o limite de confiança de 95% (p<0.05). A normalidade dos dados foi testada utilizando o teste de Shapiro-Wilk e Levene (p> 0,05) e os dados apresentados em média e desvio padrão. Foram identificadas 131 proteínas, sendo que 28 destas foram comuns a todos os grupos. 12 semanas de treinamento resistido em ratos modula proteínas que favorecem as adaptações celulares benéficas ao exercício. Porém, a inatividade, representada pelo sedentarismo, promove aumento de proteínas que podem levar ao maior comprometimento do tecido muscular. ________________________________________________________________________________________________ ABSTRACT / Sarcopenia is a multifactorial process characterized by loss of strength and skeletal muscle mass, which leads to a reduction of muscle cross-sectional area (CSA). Resistance training (RT) have been indicated as an import tool to reduce sarcopenia, however, the proteomic analysis of the muscle of old rats after TR is poor studied. The aim of the present study was to analyze the effect of RT on gastrocnemius proteome profile of old rats. Twenty-four Rattus norvegicus with 3 months (298,74 ± 32,32g) and 21 months (517,83 ± 76,30g) were divided into young sedentary (YS, n = 6), young trained (YT, n = 6), old sedentary (OS, n = 6) and old trained (OT, n = 6). Twelve-weeks of resistance training period was performed, which consisted of climbing a vertical ladder (1.1 m, 0.18 m, 2-cm grid, 80 ° incline) with a load secured to their tails. The size of the ladder induced the animals to perform 8–12 movements per climb. TF was carried out three times a week (Mondays, Wednesdays and Fridays) for 12 weeks. The climbs were to carry a progressive load of 65, 85, 95 and 100% of the maximum load capacity of each animal. After the last training session, the gastrocnemius muscle was extracted and protein compounds were analyzed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Samples were identified using Uniprot / Swissprot database. Proteins were considered covered when the score of the peptides was greater than the minimum score for the 95% confidence level (p <0.05). Data normality was tested using the Shapiro-Wilk and Levene test (p> 0.05) and data presented as mean and standard deviation. One-hundred and third-one proteins were identified, 28 were common between all groups. 12 weeks of training resistance in rats modulates proteins that promote cell beneficial adaptations to exercise. However, inactivity, represented by sedentary, promotes an increase of protein that may lead to further impairment of muscle tissue.

Tese (doutorado)—Universidade de Brasília, Faculdade de Ceilândia, Programa de Pós-Graduação em Ciências e Tecnologia em Saúde, 2015. / Submitted by Fernanda Percia França (fernandafranca@bce.unb.br) on 2015-11-20T20:37:44Z No. of bitstreams: 1 2015_LuizSinésioSilvaNeto.pdf: 2387947 bytes, checksum: 074381404e2a2bd8cf737fbc85733053 (MD5) / Approved for entry into archive by Raquel Viana(raquelviana@bce.unb.br) on 2016-05-12T20:49:12Z (GMT) No. of bitstreams: 1 2015_LuizSinésioSilvaNeto.pdf: 2387947 bytes, checksum: 074381404e2a2bd8cf737fbc85733053 (MD5) / Made available in DSpace on 2016-05-12T20:49:12Z (GMT). No. of bitstreams: 1 2015_LuizSinésioSilvaNeto.pdf: 2387947 bytes, checksum: 074381404e2a2bd8cf737fbc85733053 (MD5) / Introdução: A tese é composta de 3 artigos descritos a seguir. O Artigo 1 teve como objetivo identificar a sarcopenia em idosos quilombolas utilizando o algoritmo proposto pelo European Working Group on Sarcopenia in Older People (EWGSOP) e verificar a sua associação com os domínios de qualidade de vida estado geral de saúde (EGS) e capacidade funcional. Métodos: Estudo transversal com 70 participantes de ambos os sexos, com idade média de 65,58±6,67 anos. Dados sociodemográficos foram coletados. A sarcopenia foi definida de acordo com as recomendações do EWGSOP. Para isso, a massa muscular (MM) foi analisada por meio do DEXA, a força de preensão palmar (FPP) por meio do dinamômetro de mão, e o desempenho físico por meio do teste de velocidade de marcha (VM). A qualidade de vida foi avaliada utilizando o questionário The Medical Outcomes Study 36-item short-form healthy survey (SF-36). Resultados: Foi identificada uma prevalência de 10% de sarcopenia na população quilombola participante. Não foram encontradas diferenças significativas para os domínios de qualidade de vida EGS e capacidade funcional entre sarcopênicos e não sarcopênicos. Conclusões: O algoritmo proposto pelo EWGSOP teve aplicabilidade clínica na população idosa quilombola. A prevalência de sarcopenia em idosos quilombolas é alta. O Artigo 2 teve como objetivo caracterizar a sarcopenia em idosos quilombolas a partir de dois critérios de classificação – Baumgartner e EWGSOP– e investigar a associação entre sarcopenia e qualidade de vida. Métodos: Estudo transversal com 70 participantes de ambos os sexos com idade média de 65,58±6,67 anos. A sarcopenia foi definida de acordo com o ponto de corte proposto por Baumgartner e com as recomendações do EWGSOP A MM e o percentual de gordura forem analisados pelo DEXA, a FPP por meio do dinamômetro de mão, e o desempenho físico pelo teste de VM. Para avaliação da qualidade de vida, foi aplicado o questionário SF-36. Resultados: A prevalência de sarcopenia foi de 15% conforme o ponto de corte proposto por Baumgartner, e de 10% considerando os critérios do EWGSOP. Idosos quilombolas muito ativos e ativos tiveram 6 vezes menos chance de desenvolver sarcopenia quando comparados com os irregularmente ativos e sedentários. A FPP teve correlação negativa com sarcopenia para ambos os critérios. Os domínios aspectos físicos e dor foram significativamente inferiores em idosos com sarcopenia, para ambos critérios de classificação. Conclusões: Dessa forma, foi verificada correlação positiva entre a sarcopenia e as variáveis de qualidade de vida em idosos quilombolas, independentemente do critério de classificação para sarcopenia proposto neste estudo. Além disso, destacamos que é importante verificar a perda de massa magra concomitantemente com a funcionalidade e o desempenho físico, pois foi observado que alguns indivíduos quilombolas com baixa massa magra não apresentaram alterações na funcionalidade e desempenho físico. O ponto de corte proposto por Baumgartner apresentou ter menor acurácia do que o viii EWGSOP por não considerar funcionalidade e desempenho físico. Porém, esse ponto de corte apresentou uma maior sensibilidade na identificação da sarcopenia, uma vez que a perda de massa magra é preditora de alterações de força e VM. O Artigo 3 teve como objetivo examinar a associação entre obesidade sarcopênica e força muscular com os domínios de qualidade de vida em idosas quilombolas e não quilombolas. Métodos: A amostra foi composta por 95 voluntárias com idade 64,91±6,05 anos, do sexo feminino, sendo 39 quilombolas e 56 não quilombolas. Todas se submeteram à análise de composição corporal (IMC e absortometria de raio-x de dupla energia DEXA). Foram classificadas como obesas sarcopênicas (OS) as idosas acometidas concomitantemente com sarcopenia, de acordo com os critérios de Baumgartner, e obesidade, de acordo com os critérios da American College of Sports Medicine ACSM. A FPP foi mensurada por meio do dinamômetro Jamar. Os indivíduos foram categorizados em grupo 1, indivíduos quilombolas obesos sarcopênicos, grupo 2, indivíduos quilombolas não obesos sarcopênicos, grupo 3, indivíduos não quilombolas obesos sarcopênicos, e grupo 4, indivíduos não quilombolas não obesos sarcopênicos. Para análise de qualidade de vida, usou-se o questionário SF-36. Resultados: A prevalência de obesidade sarcopênica na amostra foi de 23,72%, ocorrendo uma maior incidência nas idosas não quilombolas. Todos os grupos apresentaram valor de percentual de gordura inadequado. As idosas quilombolas obesas sarcopênicas apresentaram piores valores de força de preensão palmar quando comparados com os grupos 2,3 e 4. Foram encontradas diferenças nos domínios EGS e aspectos sociais de qualidade de vida entre os grupos 2 e 4. Conclusões: A FPP apresentou ser uma medida importante na avaliação de OS, em especial nas idosas quilombolas obesas sarcopênicas. Não foi encontrada associação entre obesidade sarcopênica e força com domínios de qualidade de vida nas idosas, independentemente da raça/etnia. _______________________________________________________________________________________________ RESUMEN / Introducción. Esta tesis está compuesta de los tres artículos descritos a continuación. El primer artículo tuvo como objetivo identificar sarcopenia en ancianos de comunidades quilombolas utilizando el algoritmo propuesto por el European Working Group on Sarcopenia in Older People (EWGSOP) y verificar su asociación con los dominios de calidad de vida. Metodología: Un estudio transversal fue realizado con 70 participantes de ambos sexos, con edad media de 65,58 ± 6,67 años. Se colectaron datos sociodemográficos. La sarcopenia fue definida de acuerdo con el algoritmo del EWGSOP. Para ello, se determinó la pérdida de masa muscular (MM) por el método DEXA, la fuerza de prensión palmar (FPP) con dinamómetro de mano, y el desempeño físico con la prueba de velocidad de la marcha (VM). La calidad de vida se estimó a través del cuestionario The Medical Outcomes Study 36-item short-form healthy survey (SF-36). Resultados: Los resultados mostraron una prevalencia del 10% de sarcopenia en la muestra. No fueron encontradas diferencias estadísticamente significativas para los dominios de calidad de vida estado general de salud (EGS) y capacidad funcional entre los sarcopénicos y no sarcopénicos. Conclusiones: El algoritmo propuesto por el EWGSOP tuvo aplicabilidad clínica en la población de adultos mayores de comunidades quilombolas. La prevalencia de sarcopenia fue elevada. El segundo artículo tuvo como objetivo caracterizar la sarcopenia en ancianos de comunidades quilombolas por medio de dos instrumentos: Baumgartner y EWGSOP Y determinar la relación entre la sarcopenia y calidad de vida. Metodología: Un estudio transversal fue realizado con 70 participantes de ambos sexos, con edad media de 65,58 ± 6,67 años. La sarcopenia fue definida de acuerdo con el punto de corte propuesto por Baumgartner y las recomendaciones del EWGSOP. La MM y el porcentaje de grasa fueron analizados por el método DEXA, la fuerza de prensión palmar (FPP) con dinamómetro de mano, y el desempeño físico con la VM. Para evaluar la calidad de vida, se aplicó el cuestionario SF-36. Resultados: La prevalencia de sarcopenia fue del 15% de acuerdo con el punto de corte propuesto por Baumgartner y del 10% según los criterios del EWGSOP. Los ancianos pertenecientes a comunidades quilombolas muy activos y activos físicamente mostraron seis veces menos posibilidades de desarrollar sarcopenia comparados con los irregularmente activos y sedentarios. La FPP presentó una correlación negativa con la sarcopenia para ambos criterios. Los dominios aspectos físicos y dolor fueron significativamente inferiores en ancianos con sarcopenia para los dos criterios de clasificación. Conclusiones: Independientemente del criterio de clasificación propuesto en el presente estudio para sarcopenia, se verificó una correlación positiva entre la sarcopenia y las variables de calidad de vida en ancianos de comunidades quilombolas. Además, fue decisivo verificar la pérdida de masa magra simultáneamente con la funcionalidad y el desempeño físico, pues fueron observados individuos con baja x masa magra que no tuvieron alteraciones en la funcionalidad y en el desempeño físico. El punto de corte propuesto por Baumgartner fue menos preciso que el propuesto por el EWGSOP, debido a que no consideró la funcionalidad y el desempeño físico. Sin embargo, Baumgartner tuvo mayor sensibilidad en la identificación de la sarcopenia, ya que la pérdida de masa magra predice las variaciones en la fuerza y VM. Finalmente, el tercer artículo tuvo como objetivo examinar la relación entre obesidad sarcopénica y fuerza muscular con los dominios de calidad de vida en ancianas pertenecientes o no a comunidades quilombolas. Metodología: La muestra estaba compuesta por 95 voluntarias con edad de 64,91 años±6,05 años, del sexo femenino, siendo que 39 pertenecían a la comunidad quilombola y 56 no. Todas se sometieron al análisis del índice de masa corporal (IMC) y absorciometría con rayos X de doble energía DEXA. Fueron clasificadas como obesas sarcopénicas (OS) las ancianas que mostraron concomitantemente sarcopenia (Baumgartner et al, 1998) y obesidad (ACSM, 2009). La FPP fue determinada por medio del dinamómetro Jamar. La clasificación fue realizada de la siguiente manera: grupo 1: quilombolas obesos sarcopénicos, grupo 2: quilombolas no obesos sarcopénicos, grupo 3: no quilombolas obesos sarcopénicos y grupo 4: no quilombolas no obesos sarcopénicos. La calidad de vida se estimó a través del cuestionario SF-36. Resultados: La prevalencia de obesidad sarcopénica en la muestra fue del 23,72% y la mayor incidencia fue en las ancianas no quilombolas. Todos los grupos evaluados mostraron un porcentaje de grasa inadecuado. Las ancianas de comunidades quilombolas obesas sarcopénicas (grupo 1) presentaron los menores valores de FPP comparadas con los grupos 2, 3 y 4. Se encontraron diferencias estadísticamente significativas entre el EGS y los aspectos sociales de la calidad de vida entre los grupos 2 y 4. Conclusiones: La FPP fue una medida importante en la determinación de las OS, especialmente en las ancianas obesas sarcopénicas de comunidades quilombolas. No fue encontrada una relación entre obesidad sarcopénica y fuerza con dominios de la calidad de vida en las ancianas, independientemente de la raza/etnia. ______________________________________________________________________________________________ ABSTRACT / Introduction: This thesis consists of the three papers described below. The first paper aimed to identify sarcopenia in older people from quilombola communities using the algorithm of the European Working Group on Sarcopenia in Older People (EWGSOP) and to determine its association with the quality of life domains overall health status (OGS) and functional capacity. Method: A transversal study was conducted with 70 participants of both sexes with a mean age of 65.58 ± 6.67 years. Sociodemographic data were collected. Sarcopenia was defined by recommendations of EWGSOP's algorithm. The algorithm suggests to determine the muscle mass (MM) loss by DEXA method, handgrip strength (HGS) with hand-held dynamometer and physical performance assessed through a gait speed (GS) test. Quality of life was estimated using the The Medical Outcomes Study 36-item short-form healthy survey (SF-36). Results: Sample showed 10% prevalence of sarcopenia. There was no statistically significant difference between sarcopenic and not sarcopenic for the domains of quality of lifeOGS and functional capacity. Conclusions: The algorithm proposed by the EWGSOP had clinical applicability in quilombola older people. Sarcopenia prevalence was high. The second paper aimed to characterize the sarcopenia and quality of life in Quilombola's Community older people through two instruments: Baumgartner and EWGSOP and to determine the association between sarcopenia and quality of life. Method: This was a cross-sectional study of 70 male and female participants with a mean age of 65.58 ± 6.67 years). Sarcopenia was diagnosed according to the Baumgartner cut-off for appendicular skeletal muscle mass, and the criteria recommended by the EWGSOP. Muscle mass (MM) and percent fat mass were analyzed by DEXA, while handgrip strength (HGS) was evaluated using a hand-held dynamometer. Physical performance was assessed through a gait speed (GS) test. Quality of life was evaluated using the SF-36. Results: The prevalence of sarcopenia was 15% according to the Baumgartner cutoff, and 10% according to EWGSOP criteria. Quilombola older people classified as physically active or very active are six times less likely to develop sarcopenia than those classified as irregularly active or sedentary. HGS was negatively associated with a diagnosis of sarcopenia according to both sets of criteria. Subjects with sarcopenia reported lower scores than those without the condition in the physical role functioning and bodily pain domains of the SF-36.Conclusions: Quality of life was positively associated with sarcopenia in this sample of quilombola older people. Additionally, the present results showed that diagnostic criteria for sarcopenia should include reductions in lean mass in addition to measures of functioning and physical performance, since some subjects showed the former symptom without any alteration of the latter two variables. Baumgartner cut-off was less precise than that proposed by the EWGSOP because it did not consider the functionality and physical performance. However, Baumgartner was more sensitive in the identification of sarcopenia, since the loss of lean body mass xii predicts changes in the strength and gait speed. Eventually, the third paper aimed to examine the relation between sarcopenic obesity and muscle strength with the domains of quality of life in older people belonging to the Quilombola's community or not. Method: Sample was composed of 95 female volunteers aged 64.91 ± 6.05 years. Thirty-nine volunteers belong to the Quilombola's community and 56 no. Body mass index (BMI) and Dual-Energy X-Ray Absorptiometry (DEXA) were analyzed for all of them. Sarcopenic Obesity (OS) was defined for female older people who showed simultaneously sarcopenia, according to Baumgartner criteria) and obesity (according to the American College of Sports Medicine). HGS was determined by Jamar dynamometer. There was the following classification: Group 1: Quilombolas sarcopenic obeses; group 2: Quilombolas no sarcopenic-obeses, group 3: no Quilombolas sarcopenic obeses and group 4: no Quilombolas no sarcopenic-obeses. Quality of life was estimated using the SF-36. Results: Sample showed 23.72% prevalence of sarcopenia. Major incidence was in older people who not belong Quilombola's Community. All tested groups showed a percentage of inadequate fat. Older people Quilombolas sarcopenic obeses (group 1) had the lowest values of HGS compared to groups 2, 3 and 4. There was statistically significant difference between State General Health (SGH) and Social Aspects (SA) of quality of life between groups 2 and 4. Conclusions: Handgrip strength was an important measurement in determining the Sarcopenic Obesity, especially in older people sarcopenic obese of Quilombola's Community. There was not relation between sarcopenic obesity and strength with domains of quality of life in older people, being independent of race / ethnicity.