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Treinamento de Contra Resistência - Hipertrofia, Quebra de Paradigmas, Saúde, Eletromiografias e Biomecânica-20210126T152718Z-001

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Treinamento de Contra Resistência - Hipertrofia, Quebra de Paradigmas, Saúde, Eletromiografias e Biomecânica/VIAS DE SINALIZAÇÃO PARA EVITAR A ATROFIA MUSCULAR MTOR, AKT, P70.pdf
VIAS DE SINALIZAÇÃO INTRACELULAR NA ATROFIA
MUSCULAR E NO TREINAMENTO RESISTIDO
título
Intracellular pathways signaling in muscle atrophy and resistance training
Juliano Machado[a], Kleverton Krinski[b], Hassan Mohamed Elsangedy[c],
Fabricio Cieslak[d], Greicely Lopes[e], Anna Raquel Silveira Gomes[f]
[a]Educador Físico graduado pela Universidade da Região de Joinville (UNIVILLE), Mestrando em Fisiologia do Exercício da
Universidade Federal do Paraná (UFPR), Curitiba, PR - Brasil, e-mail: jumachado17@yahoo.com.br
[b]Educador Físico graduado pela Universidade Paranaense (UNIPAR), Mestrando em Atividade Física e Saúde da Universidade
Federal do Paraná (UFPR), Curitiba, PR - Brasil, e-mail: klevertonkrinski@hotmail.com
[c]Educador Físico graduado pela Universidade Paranaense (UNIPAR), Mestrando em Atividade Física Saúde pela Universidade
Federal do Paraná (UFPR), Curitiba, PR - Brasil, e-mail: hassanme20@hotmail.com
[d]Educador Físico graduado pela Universidade Estadual de Ponta Grossa (UEPG), Mestrando em Atividade Física e Saúde da
Universidade Federal do Paraná (UFPR), Curitiba, PR - Brasil, e-mail: facieslak@gmail.com
[e]Educadora Física graduada pela Universidade Federal do Paraná (UFPR), Mestrando em Fisiologia do Exercício pela
Universidade Federal do Paraná (UFPR), Curitiba, PR - Brasil, e-mail: greicielylopes@hotmail.com
[f]Fisioterapeuta graduada pela Pontifícia Universidade Católica do Paraná (PUCPR), Doutorado em Ciências Fisiológicas pela
Universidade Federal de São Carlos (UFSCAR), Professora do curso de Fisioterapia e do Programa de Mestrado e Doutorado
em Educação Física da Universidade Federal do Paraná (UFPR), Curitiba, PR - Brasil, e-mail: annaraquelsg@gmail.com
Resumo
INTRODUÇÃO: A atrofia muscular é caracterizada como um decréscimo da área de secção transversa
da fibra muscular e conteúdo de proteína muscular, reduzida produção de força, aumentada resistência à
insulina tão bem como, na maioria das vezes, transição do tipo de fibras lentas para rápidas. Os decréscimos
na taxa de síntese proteica e aumento na taxa de degradação são responsáveis pela perda de massa
muscular induzida pelo desuso, no entanto, esses mecanismos estão começando a ser elucidados por
causa da evolução das técnicas de biologia molecular, as quais permitiram um melhor entendimento das
vias de sinalização e as proteínas-chave envolvidas no processo de atrofia muscular induzida pelo desuso.
OBJETIVO: o presente estudo realizou uma revisão de literatura referente à atrofia muscular induzida
pelo desuso e suas vias de sinalização. METODOLOGIA: realizou-se uma busca de estudos indexados
às bases de dados Lilacs, Pubmed/Medline e Scielo, entre o período de 01/01/1997 a 30/06/2008, utilizando
as combinações das seguintes palavras-chave: atrophy AND skeletal muscle AND disuse AND lysosomal;
atrophy AND skeletal muscle AND disuse AND calpain; atrophy AND skeletal muscle AND disuse
AND caspase; atrophy AND skeletal muscle AND disuse AND ubiquitin-proteasome. RESULTADOS
E CONCLUSÃO: a partir dessa busca, selecionaram-se cinco artigos e, após sua leitura, buscou-se 35
artigos referenciados por estes, que além das palavras-chave anteriormente descritas incluíam o exercício
resistido como terapêutica para a atrofia muscular induzida pelo desuso. Verificou-se de acordo com os
estudos apresentados na revisão atual, que o treinamento contra a resistência pode atuar como uma
importante modalidade terapêutica para atenuar ou reverter a atrofia muscular induzida pelo desuso.
Palavras-chave: Atrofia muscular. Síntese proteica. Proteólise. Exercício.
ISSN 0103-5150
Fisioter. Mov., Curitiba, v. 22, n. 3, p. 383-393, jul./set. 2009
Licenciado sob uma Licença Creative Commons
Fisioter Mov. 2009 jul/set;22(3):383-393
384 Machado J, Krinski K, Elsangedy HM, Cieslak F, Lopes G, Gomes ARS.
Fisioter Mov. 2009 jul/set;22(3):383-393
Abstract
INTRODUCTION: The muscular atrophy is characterized as a decrease in cross-sectional area of
muscle fiber and protein content of muscle, reduced production of strength, increased resistance to
insulin as well as, commonly, transition from slow to fast fibers. The decreases in the rate of
protein synthesis and increase in the rate of degradation are responsible for loss of muscular mass
induced by disuse, however, these mechanisms are beginning to be elucidated due to of developments
in the molecular biology techniques which enabled a better understanding of signaling pathways
and the key proteins involved in muscle atrophy induced by disuse. OBJECTIVE: this study was
to make a review of literature concerning the muscular atrophy induced by disuse and their pathways
of signaling. METHODOLOGY: the search was carried in the Lilacs, Pubmed/Medline and Scielo,
limited 01/01/1997 to 30/06/2008, with the terms atrophy AND skeletal muscle AND disuse
AND lysosomal; atrophy AND skeletal muscle AND disuse AND calpain; atrophy AND skeletal
muscle AND disuse AND caspase; atrophy AND skeletal muscle AND disuse AND ubiquitin-
proteasome. RESULTS AND CONCLUSION: It was found 5 articles and after reading it was
searched 35 papers referred from them that presented resistance exercise as therapeutic to skeletal
muscle atrophy induced by disuse beyond the key-words described above. It was verified according
to studies presented in the current review that the resistance training can serve as an important
therapeutic tool to attenuate or reverse muscle atrophy induced by disuse.
Keywords: Muscle atrophy. Protein synthesis. Proteolysis. Exercise.
SIGLAS E ABREVIAÇÕES
4E-BP1 – proteína de ligação 1 do fator de iniciação eucariótico 4;
Akt – proteína quinase B, também conhecida como Akt;
Bak – antagonista/matador homólogo do Bcl-2;
Bax – proteína X associada ao Bcl-2;
Bcl-2 – linfoma 2 da célula B;
eIF – fator de iniciação eucariótico;
FoxO – fatores de transcrição “Forkhead” da família da FoxO;
GSK-3β - proteína quinase da glicogênio-3β;
IGF-1 – fator de crescimento semelhante à insulina 1;
IKB – inibidor do NF-kB;
IKKβ – proteína quinase do IKB;
IGF-1Ea – fator de crescimento semelhante à insulina sistêmica;
IGF-BP – proteína de ligação do IGF;
MAFbx – muscle atrophy F-box;
MGF – fator de crescimento mecânico;
MIKK – IKK específico do músculo;
MuRF1 – muscle RING-finger protein-1 ou atrogina;
mTOR – alvo da rapamicina de mamíferos;
MyoD – membro da família dos fatores de diferenciação miogênicos;
NF-kB – família do fator de transcrição nuclear kappa-B;
PI3K – fosfatidilinositol 3 quinase;
p70S6k – proteína quinase S6 ribossômica;
p21-Waf1 – inibidor das quinases dependentes das ciclinas;
TNF-α – fator de necrose tumoral alfa.
385Vias de sinalização intracelular na atrofia muscular e no treinamento resistido
Fisioter Mov. 2009 jul/set;22(3):383-393
INTRODUÇÃO
Condições como redução nos padrões habituais de atividade física, repouso no leito,
permanência em cadeira de rodas, imobilização, câncer, sepsis, doenças autoimunes, desnervação,
exposição à microgravidade podem levar à perda de massa e capacidade músculo-esquelética (1). A
proteólise músculo esquelética induzida por estas condições é um fenômeno conhecido como atrofia
muscular, e as consequências funcionais e morfológicas comuns em todas estas formas de atrofia são:
diminuída área de secção transversa da fibra muscular e do conteúdo proteico, reduzida produção de
força e potência, aumentada fatigabilidade e aumentada resistência à insulina (2-6).
O desuso da musculatura esquelética por causa da diminuição da sobrecarga imposta leva
a um decréscimo na taxa de síntese proteica e um aumento na taxa de degradação proteica (1, 7, 8), no
entanto, muitas moléculas ativadoras que estão envolvidas na atrofia muscular são pouco conhecidas.
Muitos avanços têm ocorrido recentemente para elucidar os mecanismos envolvidos na degradação
proteica
intracelular, possibilitando um maior entendimento dos ativadores ligantes, e dos
mecanotransdutores de sinais das vias de sinalização que levam à proteólise muscular (1, 9, 10).
Diante disso, o objetivo desta revisão é relatar os achados mais recentes dos artigos
publicados nos últimos dez anos, bem como alguns estudos clássicos que permitiram construir o
conhecimento atual, sobre as moléculas de sinalização intracelular envolvidas na atrofia muscular
induzida pelo desuso e na caquexia, assim como os efeitos da terapêutica relacionada ao treinamento
contra resistência sobre estas vias de sinalização.
METODOLOGIA
O presente estudo foi realizado mediante uma pesquisa de estudos indexados às bases de dados
Lilacs, Medline, Pubmed e SciELO entre 01/01/1997 a 30/06/2008. Para seleção dos artigos utilizaram-se
parâmetros relacionados às vias de sinalização para atrofia muscular induzida pelo desuso, perfazendo as
seguintes combinações de palavras: atrofia e vias lisossomais “atrophy and skeletal muscle and disuse and
lysosomal”, atrofia e vias calpaínas “atrophy and skeletal muscle and disuse and calpain”, atrofia e vias
das caspases “atrophy and skeletal muscle and disuse and caspase” e atrofia e ubiquitina-proteasoma
“atrophy and skeletal muscle and disuse and ubiquitin-proteasome”. Como critérios de inclusão foram
utilizados artigos que continham em seu título alguma das palavras-chave das combinações descritas e que
não se repetiam em outra base de dados. Desta forma, foram encontrados 35 artigos no Pubmed e
selecionados apenas quatro artigos, já no Medline foram encontrados 43 artigos e selecionado apenas um.
Não foram encontrados artigos nas bases de dados Lilacs e SciELO com esses critérios.
Diante disto, os 5 artigos encontrados nas bases anteriormente descritas apresentavam
citações literárias que estavam de acordo com os critérios da revisão atual e que também apresentavam
o exercício contra resistência como forma terapêutica para o tratamento da atrofia muscular induzida
pelo desuso. Assim, outros 35 artigos, retirados de referências dos 5 artigos encontrados nas bases,
foram pesquisados, lidos e incluídos nesta revisão.
RESULTADOS E DISCUSSÃO
Vias de sinalização envolvidas na atrofia muscular induzida pelo desuso
Existem quatro vias proteolíticas conhecidas que levam à atrofia muscular: a via de sinalização
das catepsinas ou lisossomais, via de sinalização das calpaínas dependentes de cálcio (Ca2+), via de
sinalização das caspases e da ubiquitina proteassoma ATP-dependente (1, 9, 10). De maneira geral, parece
386
que as proteínas clivadas são degradadas no proteassoma, no entanto, o entendimento sobre as moléculas
ativadoras envolvidas no decréscimo da síntese proteica, como o IGF-1, FoxO, os sinais de mecanotransdução
da titina e os fatores de transcrição NF-kB estão começando a ser conhecidas.
Via de sinalização lisossomal
Os lisossomos são organelas encapsuladas que contêm grande número de proteases conhecidas
como catepsinas B, D, H e L, tão bem como outras hidrolases ácidas. Tem-se verificado que nove dias de
suspensão da pata traseira de ratos resulta em atrofia muscular e acentuada proteólise no sóleo (11). Além
do mais, as medidas in vitro mostraram que a atividade das catepsinas B, B+L e calpaína-m aumentaram
em 111%, 92% e 180% respectivamente, juntamente com uma aumentada concentração do RNAm destas
proteinases (11). No entanto, as vias proteolíticas, tanto dependentes de cálcio como a lisossomal,
apresentam uma pequena influência sobre a proteólise total, ou seja, 9% nos músculos controle e 18% nos
atrofiados (11). Essas observações são consistentes com a atual visão de que as catepsinas não degradam
proteínas citosólicas, como às proteínas miofibrilares, ao invés disso, seu maior papel está na degradação
de proteínas de membrana tais como receptores, canais de íons, transportadores (1).
Recentemente (12), demonstrou-se o que a proteólise dependente da autofagia/lisossomal
apresenta mecanismos mais complexos após examinarem músculos de ratos que estão se atrofiando pela
desnervação. Neste contexto, observou-se diminuída atividade da via de sinalização do IGF1/PI3K/
Akt e aumentada autofagia por meio do fator de transcrição FoxO3, mostrando uma regulação
coordenada entre os sistemas proteassomal e lisossomal (12). Essas evidências nos mostram o quanto
os mecanismos indutores de atrofia operam harmonicamente um com o outro, contudo, pouco se sabe
sobre como todos esses mecanismos operam.
Via de sinalização das calpaínas dependentes de Ca2+
As calpaínas são proteases cisteínas dependentes de Ca2+ que constituem uma grande e
diversa família. As fibras músculo-esqueléticas contêm as calpaínas-1 e -2, e uma calpaína específica
do músculo conhecida como calpaína -3 ou p94 (13). Pouco se sabe sobre os precisos papéis das
calpaínas na regulação normal da musculatura esquelética, embora provavelmente elas estejam
envolvidas na organização do citoesqueleto, ciclo celular e apoptose (13).
O aumento nas concentrações de Ca2+ intracelulares pode ativar as calpaínas concentradas
no disco-Z (9). Além do mais, as calpaínas degradam proteínas como a fodrina, um substrato bem
caracterizado das calpaínas, a nebulina, uma importante proteína da arquitetura do sarcômero (14), a
titina, proteína-C, vinculina, entre outras, nos quais são substratos conhecidos das calpaínas (1). Assim,
a clivagem da titina, proteína que mantém o alinhamento do sarcômero, permite a liberação das
miofibrilas para serem ubiquitinadas e, subsequentemente, degradadas no proteassoma (9), pois o
proteassoma não é capaz de degradar proteínas intactas. Tem-se mostrado recentemente em ratos com
a pata traseira imobilizada, que as calpaínas-1 e -2 estão envolvidas no desenvolvimento da atrofia em
músculos com a característica predominantemente oxidativa e que as vias proteolíticas parecem diferir
em músculos predominantemente lentos e rápidos (14).
Via de sinalização das caspases
As caspases constituem um grupo de família de proteases de cisteína – peptidases que usam
um resíduo de cisteína como nucleófilo catalítico – que dividem uma especificidade para clivar proteínas
alvos nos sítios próximos ao ácido aspártico. As caspases são responsáveis pela apoptose ou morte
celular programada, que é essencial para o desenvolvimento embrionário e de muitas doenças (15).
Machado J, Krinski K, Elsangedy HM, Cieslak F, Lopes G, Gomes ARS.
Fisioter Mov. 2009 jul/set;22(3):383-393
387
A ativação da caspase-3 por meio da conexão entre a via de sinalização da PI3K/Akt e
ativação das vias proteolíticas tem sido mostrado recentemente, e esta, têm um importante papel na
atrofia muscular induzida por doenças como o câncer e o diabetes (16, 17).
Sabe-se que o sistema proteolítico ubiquitina proteassoma é capaz de degradar monômeros de
actina ou miosina, no entanto, esse sistema não é capaz de quebrar os complexos actomiosina intactos (10).
Neste sentido, as caspases podem ter ações similares às calpaínas em tornar as proteínas miofibrilares
disponíveis para a ubiquitinação (1). Assim, foi mostrado que o tratamento dos complexos de actomiosina
solúveis da musculatura esquelética de ratos diabéticos com caspase-3 recombinante levava a uma
acentuada proteólise (17). Embora prévios estudos tenham buscado investigar elucidar os mecanismos das
caspases, não existem evidências mostrando o seu papel na atrofia muscular induzida pelo desuso.
Via de sinalização da ubiquitina proteassoma
O proteassoma 26S é um grande complexo multiproteico que consiste do centro proteolítico
20S e dois “anéis” o 19S, nos quais regulam a ligação e a degradação das proteínas ubiquitinadas (1).
A degradação da maioria das proteínas miofibrilares decorrente da atrofia ocorre no proteassoma, e o
processo de ubiquitinação envolve a cooperativa interação das três classes de proteínas determinadas
E1 ou ativante de ubiquitina, E2 ou conjugante de ubiquitina e a E3 ou ligante de ubiquitina (1, 9, 18).
A ubiquitina é primeiramente
ativada por meio da ação da E1 num processo dependente de ATP. A
ubiquitina ativada é então transferida para a E2, e em seguida a enzima E3, a qual encontra-se ligada
à proteína substrato que será marcada para ser degradada, se liga à E2. Neste sentido, a E2 transfere a
ubiquitina para a proteína-alvo ligada na E3 marcando-a para a posterior morte no proteassoma. Esse
processo é repetido até uma cadeia de quatro ou mais moléculas de ubiquitina ter sido formada, para que
seguidamente a proteína-alvo seja degrada em pequenos peptídeos no proteassoma (9).
TRANSDUÇÃO DE SINAL E PROTEÓLISE NA ATROFIA MUSCULAR
Relação entre a via da PI3K-Akt e FoxO na atrofia muscular
Tem-se mostrado que miotúbulos em cultura no estado de atrofia, a atividade da via da PI3K/
Akt diminui, levando a ativação dos fatores de transcrição FoxO e ativação da atrogin-1/MAFbx, e que
o tratamento com IGF-1 ou a expressão exacerbada da Akt inibe a expressão da atrogin-1 (19). Assim, os
fatores de transcrição FoxO têm papel crítico no desenvolvimento da atrofia muscular, e a inibição desses
fatores é uma atrativa abordagem para combater o processo de atrofia induzida pelo desuso.
Em um estudo foi mostrado que ratos transgênicos, hiper-expressando a FoxO1, mostraram
um decréscimo significativo no tamanho das fibras do tipo I e do tipo II, além de um decréscimo no
número de fibras do tipo I (20). Por outro lado, a atividade de corrida realizada na esteira significativamente
reduziu a atividade da FoxO1 nos ratos transgênicos em comparação aos ratos controle (20).
Verificou-se recentemente que humanos com doença pulmonar obstrutiva crônica, tanto em
estado de atrofia muscular como em estado normal (controle), os níveis das proteínas FoxO1, Akt e 4E-
BP1 estavam aumentados (21). Além disto, as concentrações do RNAm das ubiquitinas ligases atrogin-
1 e MuRF1 estavam aumentadas em sujeitos com atrofia em comparação aos sujeitos controle (21).
Neste sentido, a regulação transcricional das ubiquitinas ligases ocorrem via FoxO1, porém, parece
ser independente da Akt, mostrando que estes indivíduos apresentam elevada expressão das vias de sinalização
hipertróficas na tentativa de restaurar massa muscular perdida (21). Contudo, essas respostas intracelulares
ainda não foram verificadas em humanos saudáveis com atrofia muscular. Isso mostra que os modelos de atrofia
muscular induzida pelo desuso precisam ser construídos utilizando como base os estudos experimentais com
modelos animais, pois pouco se sabe sobre os mecanismos ativadores desta via, principalmente em humanos.
Vias de sinalização intracelular na atrofia muscular e no treinamento resistido
Fisioter Mov. 2009 jul/set;22(3):383-393
388
NF-kB como molécula de sinalização na atrofia muscular
O fator de transcrição nuclear kappa-B (NF-kB) é um complexo proteico o qual foi mostrado
que está envolvido no processo de atrofia por desuso. Em mamíferos, existem cinco tipos diferentes de
NF-kB (p65 ou Rel A, Rel B, c-Rel, p52 e a p50), nos quais medeiam uma variedade de processos de
acordo com o tipo de célula e dos ativadores específicos (10).
A ativação do NF-kB se dá por meio da ubiquitinação e degradação de sua proteína inibitória
IkB, que em estado normal encontra-se ligada ao NF-kB mantendo-o no citoplasma (10). Por exemplo,
na via clássica ou canônica, o TNFá ativa a fosforilação de uma quinase do IkB, IKKâ, que por sua vez
estimula a degradação do IkB, permitindo a translocação do heterodímero p65/p50 para o núcleo,
porém, quando o IkB é ativado pelo IKKá, a via de ativação é a não-canônica do NF-kB (10).
Tem-se mostrado que sete dias de suspensão da pata traseira de ratos, marcadamente
autorregula os níveis nucleares da p50, enquanto a c-Rel é moderadamente autorregulada, a Rel B baixo-
regulada, e a p52 e p65 não sofreram mudanças (22). Foi verificado também que durante esse período,
os membros da família do NF-kB ativados pelo desuso são completamente diferentes dos membros
ativados pela caquexia (22). Outro fator que vale ressaltar é que as concentrações da proteína anti-
apoptótica Bcl-2 estavam aumentadas em quatro vezes, enquanto as proteínas pró-apoptóticas Bax e
Bak demonstravam concentrações reduzidas (22).
Recentemente demonstrou-se que um período de três a sete dias de suspensão da pata
traseira ativa genes envolvidos na atrofia como a atrogin-1, FoxO3a entre outros, nos quais parecem ser
alvos dos fatores de transcrição NF-kB (23). Neste sentido, a degradação do IkBá é um fator necessário
para atrofia induzida pelo desuso, por meio do aumento na ubiquitinação da proteína IkB e ativação da
via de sinalização do NF-kB e a expressão de genes alvos envolvidos na atrofia muscular (23).
Porém, é possível que a ativação das vias de sinalização canônica e não-canônica do NF-kB
na atrofia muscular induzida pelo desuso sejam ativadas de forma tempo dependente. Pois o NF-kB é
ativado bifasicamente na musculatura esquelética de ratos tanto jovens como idosos durante quatro
semanas de imobilização, com um decréscimo na atividade da via clássica do heterodímero p65/p50 nas
primeiras duas semanas, seguido por um aumento na atividade deste heterodímero nas próximas duas
semanas (24). Estes achados são consistentes com os achados publicados previamente nos quais
mostraram uma ativação da via alternativa do NF-kB seguindo a atrofia por desuso (22, 23).
Um estudo recente mostrou existir um componente acima do NF-kB, a IkB quinase-â
(MIKK), o qual causa intensa proteólise (25). Foi verificada uma perda de massa muscular através da
proteólise dependente da ubiquitina, pois a expressão da ubiquitina ligase MuRF1 estava aumentada em
ratos com a forma constitutivamente ativa do MIKK (25). Além do mais, a inibição farmacológica do
eixo IKKâ/NF-kB/MuRF1 reverteu a atrofia, levando a uma atenuada proteólise induzida pela
desnervação ou tumor seguido de uma aumentada taxa de sobrevivência (25).
Neste sentido, a sinalização do NF-kB é um componente central do processo de atrofia
e pode estar envolvida na ativação dos processos proteolíticos. A partir desses achados, pode-se
sugerir que os músculos imobilizados ou aqueles que estão em estado de atrofia por desuso, sofram
um processo inflamatório, o qual pode apresentar uma variação tempo dependente levando à ativação
da via do NF-kB.
Efeitos do treinamento contra resistência sobre a atrofia muscular
Tem-se mostrado que a aumentada sobrecarga, resultante do exercício crônico, conduz a
uma aumentada expressão do gene que codifica o IGF-1 tanto em modelos animais (26) como em
humanos (27). Além do mais, duas seletivas isoformas do IGF, o IGF-1Ea e o fator de crescimento
mecânico (MGF) parecem ser seletivamente expressos na musculatura esquelética e regulados pela
sobrecarga mecânica, nos quais apresentam efeitos parácrino e autócrino (28).
Machado J, Krinski K, Elsangedy HM, Cieslak F, Lopes G, Gomes ARS.
Fisioter Mov. 2009 jul/set;22(3):383-393
389
Desta forma, a ativação da PI3K por meio de um ligante em seu receptor específico, tal como
o IGF-1, fosforila o fosfolipídeo de membrana fosfatidilinositol-4,5-bifosfato para fosfatilinositol-
3,4,5-trifosfato, criando um sítio de ligação na membrana plasmática para a proteína serina/treonina
Akt (29, 30). A Akt em seu estado ativado/fosforilado, fosforila a proteína quinase alvo da rapamicina
dos mamíferos (mTOR), produz um aumento na síntese proteica por meio da ativação da p70S6K e da
4E-BP1, os quais são reguladores-chave envolvidos na tradução e síntese proteica (29, 30).
A ativação das vias de sinalização do mTOR tem importante papel em regular o crescimento
muscular e a hipertrofia músculo-esquelética (31). O treinamento resistido de alta intensidade tem
mostrado alterar o perfil dos polissomos, sugerindo que a taxa de iniciação da tradução é aumentada por
esse tipo de treinamento (32). Além do mais, existe uma forte correlação entre a ativação da p70S6K,
um regulador da iniciação da tradução, com os aumentos na massa muscular (32). Neste sentido,
é
possível inferir que realizar um treinamento com intensidades superiores à intensidade de treino
observada em protocolos clássicos como o de De Lorme, possam causar melhores resultados sobre a
atrofia muscular induzida pelo desuso, porém é preciso estudos que comprovem essa teoria.
O exercício resistido também induz um transitório aumento na fosforilação do mTOR (33),
PKB/Akt (34), 4E-BP (35) e S6K1 (32), assim como na atividade do eIF2 (36, 37). Além do mais,
parece existir uma ativação dependente do tempo dos mecanismos anabólicos e miogênicos que levam
ao aumento miofibrilar. Um único período de exercício de contrações isométricas máximas em humanos,
por meio da estimulação elétrica neuromuscular do músculo vasto lateral, com estímulos de 5 segundos
e repouso de 15 segundos durante 30 minutos, onde as contrações evocadas eram em séries de 50 Hz
e pulsos bifásicos de 450 µs, com o intuito de mimetizar um período de exercício resistido, resultou em
uma série de alterações anabólicas na musculatura exercitada (38). Este protocolo resultou em
aumentados níveis do RNAm para a proteína de ligação-4 do IGF, a IGFBP-4 (84%), MyoD (83%),
miogenina (aproximadamente 3 vezes), ciclina D1 (50%), p21-Waf1 (16 vezes), um transitório
decréscimo no RNAm do IGF-1 (38). Já os RNAm para o MGF, IFGBP-5 e do receptor do IGF-1 não
apresentaram alteração, no entanto, 72 horas após a sessão, todos estes RNAm estavam aumentados
(38), mostrando um efeito anabólico do treinamento resistido.
Outra característica importante do treinamento resistido é a combinação de ações musculares
(concêntrica, excêntrica e isométrica) com o objetivo de reverter ou minimizar a atrofia muscular
induzida pelo desuso. Tem-se mostrado que a combinação das ações dinâmicas com as isométricas com
suficiente volume apresenta importante estímulo anabólico e miogênico que se contrapõem aos estágios
inicias da atrofia muscular induzida pelo desuso. Além destes efeitos, o treinamento resistido também
elevou a expressão e fosforilação das proteínas quinases envolvidas nas respostas anabólicas, como a
Akt, mTOR e a proteína glicogênio sintase quinase-3b (GSK-3b), em paralelo com um decréscimo do
conteúdo da FoxO1 no núcleo (fator de transcrição envolvido na atrofia muscular) (39). Esses
resultados mostram a nível molecular que umas das adaptações do treinamento resistido são os
aumentos nas alterações anabólicas juntamente com um leve decréscimo nas alterações catabólicas,
resultando em um equilíbrio nitrogenado positivo e aumento da massa muscular.
Diante de todas essas informações, é importante salientar também a necessidade de se
manter os níveis de treinamento para que os ganhos positivos sobre a massa muscular esquelética
sejam mantidos, pois o treinamento resistido de oito semanas em humanos resultou em hipertrofia
muscular (10%) juntamente com um aumento no conteúdo das proteínas Akt, GSK-3b e mTOR em
seus estados fosforilados, em paralelo com um decréscimo do conteúdo da FoxO1 nuclear (39).
Porém um período de destreinamento de oito semana o qual simulou o desuso, causou 5% de atrofia
muscular, um decréscimo na Akt e GSK-3b nos seus estados fosforilados e um aumento na FoxO1
nuclear, em relação aos resultados obtidos no período pós-treinamento (39). Além do mais, logo após
o período de treinamento foi observado um aumento nas ubiquitinas ligases atrogina 1 e MuRF1 (fase
de hipertrofia), no entanto, ocorreu um decréscimo destas ubiquitinas logo após o período de
destreinamento (fase de atrofia) (39).
Vias de sinalização intracelular na atrofia muscular e no treinamento resistido
Fisioter Mov. 2009 jul/set;22(3):383-393
390
Uma atual teoria mostra que um decréscimo na atividade/sobrecarga muscular diminui a
sinalização dos fatores de crescimento, resultando num decréscimo da fosforilação da FoxO pela Akt. Na
sua forma hipofosforilada, a FoxO transloca para o núcleo e aumenta a expressão de genes da atrofia como
as proteínas ubiquitinas ligases atrogin-1 e a MuRF1 (8), além do mais, esta última também é regulada pelo
NF-kB (40). As proteínas MuRFs (-1, -2, -3) interagem com o domínio quinase da titina, num músculo ativo
e, assim, mantendo-se fortemente ligada à titina, porém, quando a ligação é quebrada, tal como pela
inatividade, a MuRF é liberada e lançada para o núcleo, aumentando a expressão de genes da degradação
proteica (8). Isto justifica a importância de se manter os níveis de treinamento físico para autorregular a
via de hipertrofia muscular, ou ao menos manter a massa muscular, principalmente se o organismo vir a
se encontrar em estado de atrofia muscular induzida pelo desuso, pois ao contrário da caquexia, a atrofia
pelo desuso pode ser completamente revertido pelo treinamento resistido.
CONSIDERAÇÕES FINAIS
A presente revisão demonstrou a interação dos mecanismos envolvidos nas vias de
sinalização da atrofia muscular induzida pelo desuso bem como no treinamento resistido. Diante de
todas as citações acima, é verificado que apesar de existirem diversas vias de sinalização intracelular que
atuam na atrofia muscular induzida pelo desuso (lisossomal, calpaínas, apoptóticas e proteassomal), a
autorregulação da via da PI3k/Akt é essencial para a manutenção da musculatura esquelética, pois ela
proporciona um efeito cascata integrando as vias de hipertrofia e atrofia muscular no desuso (Figura 1).
Desta forma, modalidades terapêuticas como o treinamento resistido têm mostrado ser eficaz em
autorregular a via de síntese proteica, o qual está baixo-regulada em estado de atrofia muscular induzida
pelo desuso, assim, o treinamento resistido estimula um aumento ou mantém a massa muscular
esquelética, contrapondo-se aos efeitos negativos gerados pela atrofia muscular causada pelo desuso.
FIGURA 1 - Comparação das vias ativadas pelo desuso e treinamento resistido
Legenda – As setas apontadas para cima indicam um aumento na expressão, as setas apontadas para baixo indicam uma diminuição da expressão da
respectiva proteína intracelular. Os sinais positivos representam ativação, já os sinais negativos inibição de uma dada proteína. No estado treinado,
existe uma maior atividade das vias anabólicas em comparação com as vias catabólicas, porém no desuso, a proteólise predomina sobre a síntese
protéica. Contudo, deve-se salientar que tanto em estado treinado como no desuso da musculatura esquelética, as vias de síntese e de degradação
protéica são ativadas, a diferença está no grau de predomínio de uma sobre a outra.
Machado J, Krinski K, Elsangedy HM, Cieslak F, Lopes G, Gomes ARS.
Fisioter Mov. 2009 jul/set;22(3):383-393
391
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Recebido: 18/08/2008
Received: 08/18/2008
Aprovado: 21/05/2009
Approved: 05/21/2009
Revisado: 23/09/2009
Reviewed: 09/23/2009
Vias de sinalização intracelular na atrofia muscular e no treinamento resistido
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Treinamento de Contra Resistência - Hipertrofia, Quebra de Paradigmas, Saúde, Eletromiografias e Biomecânica/TREINAMENTO RESISTIDO COM DIFERENTES FREQUENCIAS SEMANAIS E RESULTADOS.pdf
 ISSN 1750-9823 (print) 
 
 
International Journal of Sports Science and Engineering
Vol. 05 (2011) No. 02, pp. 112-118
Effects of 8 Weeks Equal-Volume Resistance Training with 
Different Workout Frequency on Maximal Strength, 
Endurance and Body Composition 
Hamid Arazi , Abbas Asadi 
Department of physical education and sport science, University of Guilan, Rasht, Iran 
(Received March 15, 2011, accepted May 9, 2011) 
Abstract. The purpose of this study was to determine the effects of short-term equal-volume resistance 
training with different workout frequency on maximal strength, endurance, and body composition in novice 
subjects. Thirty-nine healthy males comprised four groups; total-body resistance training (12 exercises for 
one session per week) (part I=10), total-body resistance training (12 exercises for two sessions per week) 
(part II=10), lower-body, upper-body, and upper-body resistance training (12 exercises for three sessions per 
week) (part III=9), and control group (CG=10). Assessments of body composition, leg and arm 
circumferences, body weight, strength (one repetition maximum in bench and leg press) and endurance 
(bench and leg press) were determined before and after 8 weeks of training. One repetition maximum in 
bench and leg press was improved significantly in all training groups (P < 0.05). All groups increased body 
weight, body composition, and bench and leg press endurance (P < 0.05),
but PIII group showed a little 
improvement rather than other groups (P > 0.05). The PIII group not only increased thigh circumference but 
also improved arm circumference, whereas the PI and PII groups changed either arm circumference or thigh 
circumference (P < 0.05). It is concluded that in healthy young men, whole and split weight training routine 
produce similar results over the first 2 months of training, with minimal differences among groups. 
Keywords: split routine, exercise performance, resistance training. 
1. Introduction 
Resistance training, also known as strength or weight training, has become one of the most popular 
forms of exercise for enhancing and individual's physical fitness as well as for conditioning athletes. 
Resistance training has been used extensively to increase fitness and sport performance. It has been 
demonstrated to augment maximum strength, power, and jumping ability (1,2,3). It is well known that a 
variety of resistance training programs can stimulate an increase in one repetition maximum (1RM) strength 
(4,5,6). However, only few studies have attempted to make direct comparisons of different styles of 
resistance training programs to determine adaptational differences. With short-term training, Marcinik et al. 
(7) compared high intensity (i.e., 70% of 1-RM) versus low intensity (i.e., 40% of 1-RM) aerobic/circuit 
resistance training in women who were U.S. Naval recruits. After 8 wk, 1-RM bench press performance was 
significantly greater in the high-intensity group, whereas no difference was observed between groups in 1-
RM leg press performances. American College of Sports Medicine (ACSM) recommends split routines to 
maximize strength gains among intermediate-advanced resistance-trained individuals and athletes. With split 
routine training paradigm, individuals train different body parts on each training session within a week to 
allow proper muscle recovery and to maximize training loads. The ACSM expands this recommendation 
suggesting that split training routines should also require the periodization of the training load (8). This has 
been shown to be an effective initial frequency whereas 1-2 d·wk_1 appears to be an effective maintenance 
frequency for those individuals already engaged in a resistance training program (9). In a few studies: 4-5 
d·wk_1 were superior to 3, 3 d·wk_1 superior to 1 and 2 d, and 2 d·wk_1 superior to 1 for increasing maximal 
strength (9,10). Performing upper/lower body split or muscle groups split routines during a workout are 
common at this level of training in addition to total-body workouts (5). 
Hakkinen et al. (11) reported greater increases in muscle cross-sectional area and strength when training 
 
 Corresponding author. Tel.: +98 911 139 9207; Fax: +98-131 6690675. 
 E-mail address: h_arazi2003@yahoo.com. 
Published by World Academic Press, World Academic Union 
International Journal of Sports Science and Engineering, 5 (2011) 2, pp 112-118 113
 
volume was divided into two sessions rather than one. Previous studies designed resistance training to upper-
body, lower-body and or total-body workouts. They reported that upper-body and total-body resistance 
training resulted in similar improvements in performances and or total conditioning program directed at 
development of muscle tissue mass (12,13). In our knowledge, no study compared the effects of designing 
resistance training, which divided into three parts; total-body resistance training one session per week (part I), 
total-body resistance training two sessions per week (part II), and upper-body, lower-body, and upper-body 
resistance training three sessions per week (part III), together. No data are available to address this question 
that; Is resistance training for 1 session better than 2, or 3 sessions, and or 3 sessions is better than 1, or 2 
sessions with equal-volume in novice subjects? Are important exercise sessions to design resistance training 
for novices and beginners? Are differences among exercise sessions for increasing physical fitness? Those 
are current questions that we want to answer in this study. Therefore, the purpose of this investigation was to 
examine the effect of three differences periodized resistance training programs (part I, part II, and part III) on 
strength, endurance, and body composition in novice subjects. 
2. Methods 
2.1. Subjects 
Thirty-nine healthy males were volunteered to participate in this study. Subjects were randomly divided 
into four groups; part I group (PI; n=10), part II group (PII; n=10), part III group (PIII; n=9), and control 
group (CG; n=10). Subjects were informed as to the experimental procedures and signed informed consent 
statements and medical history forms in adherence with the human subjects’ guidelines of the University of 
Guilan Health Sciences Center before any data collection. Subjects had been never involved any type of 
resistance training and had normal dietary intake during the study. There were no significant differences 
among groups in age, height, weight, and percent body fat at pre training (Table 1). 
Table 1. Subjects characteristics. Data are mean ± SD. 
 PI PII PIII CG 
Age (yr) 20.20±1.87 20.40±2.31 20.33±1.80 20.40±2.06 
Height (cm) 173.60±3.80 174.20±5.18 175.67±5.29 174.40±5.05 
Weight (kg) 70±4.49 72.15±8.28 73.33±7.63 74.15±5.61 
Body fat (%) 13.54±2.72 13.74±2.92 14.13±2.86 13.20±3.49 
2.2. Testing Procedures 
The subjects were familiarized with the resistance training program about one week before the start of 
training period. During the familiarization session, subject initial characteristics such as; age, height, body 
weight, percent body fat, thigh and arm circumference, one repetition maximum (1RM) and endurance (60% 
1RM) for bench press and leg press, were obtained. 
Subjects were tested pre training and post training (8 weeks). The same researchers conducted all tests. 
Pre and post training anthropometric measures of weight, and percent body fat were taken. Height was 
measured to a nearest to 0.1 cm using height rod. Body weight with minimal clothing was measured to the 
nearest 0.1 kg on a lever-type balance in a fasted state after emptying the bladder. Subjects had 3 skin fold 
sites (chest, abdominal, and thigh) measured to determine body composition or percent body fat. The 
measurement was used the method of Jackson and Pollock (14). The circumference of mid thigh and mid 
upper arm of the dominant limbs was assessed. 
A bilateral leg press test was selected to provide data on maximal strength through the full range of 
motion of the muscles involved. Maximal strength of the lower extremity muscles was assessed using 
concentric 1RM leg press action. Bilateral leg press tests were completed using standard leg press equipment 
(NIROO, KING BODY, IRAN), with the subjects assuming a sitting position and the weight sliding 
obliquely at 45˚. On command, the subjects performed a concentric leg extension (as fast as possible) 
starting from the flexed position to reach the full extension against the resistance determined by the weight. 
Warm-up consisted of a set of 10 repetitions at loads of 40-60% of the perceived maximum. 
For the bench press, each participant lowered the bar until contact with the chest was achieved and 
subsequently lifted the bar back to the fully extended elbow position. Any trials failing to meet the 
standardized technique criteria were discarded. A warm-up consisting of 5-10 repetitions with approximately 
40-60% of perceived maximum was performed. The rest period between the actions was always 2 minutes. 
SSci email for subscription: publishing@WAU.org.uk 
Hamid Arazi, et al: Effects of 8 Weeks Equal-Volume Resistance Training with Different Workout Frequency 114
Subjects
were allowed to perform maximum 8 repetitions during bench press and leg press, and were used 
equation of Brzycki (15) for the determine of 1RM. 
)0278.0(0278.1
)(
1
srepetitionofnumber
kgweight
RM

 
The local muscular endurance test was conducted 24 hours after maximal strength tests. The test was 
accomplished by execution of repetitions to exhaustion. After a short period of light aerobic warm-up, 
participants performed as many repetitions as possible without stopping or pausing between repetitions. The 
resistance comprised 60% of 1RM (16). The exercises selected for the application of this test were the bench 
and leg press. 
2.3. Resistance Training 
All workouts started with a general warm-up and included cool-down periods (i.e., low-intensity aerobic 
exercise, stretching, etc.) of approximately 5-10 min. A trainer supervised all subjects so that all essential 
program characteristics were strictly enforced. Specifically, trainers were responsible for seeing that exercise 
prescriptions were properly carried out and achieved during a workout (e.g., velocity of movement, 
appropriate spotting, appropriate safety considerations, prescribed rest periods, and proper hydration 
requirements). Also, it has been recently demonstrated that direct supervision of resistance training is vital to 
optimize strength performance adaptations (17). The 8 weeks program consisted of free weight and machine 
exercises. The part I group performed all upper- and lower-body exercises in one training session per week 
(Saturday) for 8 weeks. Resistance training program included; leg press, leg curl, leg extension, calf raise, lat 
pull-down, lat pull-row, bench press, pack fly, arm curl, dumbbell arm curl, triceps push-down, and 
dumbbell triceps extension (Table 2). The part II group performed upper- and lower-body exercises in two 
training sessions per week (Saturday and Tuesday) for 8 weeks. Resistance training program included; leg 
press, leg curl, lat pull-down, bench press, arm curl, and triceps push-down on Saturday; and leg extension, 
calf raise, lat pull-row, pack fly, dumbbell arm curl, and dumbbell triceps extension on Tuesday (Table 2). 
The part III group performed lower-body, upper-body and upper-body exercises in three training sessions per 
week (Saturday, Monday, and Wednesday) for 8 weeks. Resistance training program included; leg press, leg 
curl, leg extension, and calf raise on Saturday; lat pull-down, lat pull-row, triceps push-down, and dumbbell 
triceps extension on Monday; bench press, pack fly, arm curl, and dumbbell arm curl on Wednesday, (Table 
2). Subjects were tested every 2 weeks, and resistance exercises were designed based on new 1RM for each 
exercise. Total training volume was not different among groups, yet training frequency was different among 
the three programs. 
Table 2. Resistance training for PI, PII, PIII groups. 
Group Exercises Week 1-2 Week 3-4 Week 5-6 Week 7-8 Rest periods 
 Reps-intensity 
PI I 12-60% 1RM 10-12-70% 1RM 8-10-75% 1RM 6-8-80%1RM 2-3 min 
PII II 12-60% 1RM 10-12-70% 1RM 8-10-75% 1RM 6-8-80%1RM 2-3 min 
PIII III 12-60% 1RM 10-12-70% 1RM 8-10-75% 1RM 6-8-80%1RM 2-3 min 
I; 12 exercises on Saturday 
II; 12 exercises on Saturday and Tuesday 
III; 12 exercises on Saturday, Monday and Friday 
1RM; one repetition maximum 
2.4. Statistical Analysis 
All data are presented as mean ± SD. A one-way analysis of variance (ANOVA) was used to determine 
significant differences among groups. In the event of a significant F ratio, Scheffe post hoc tests were used 
for pairwise comparisons. Paired t-tests were used to identify any significant differences between the groups 
at the pre and post tests for the dependent variables. A criterion α level of P ≤ 0.05 was used to determine 
statistical significance. 
3. Results 
The results of this study are presented in figure 1. There were significant changes in the percent body fat, 
weight, 1RM bench press and 1RM leg press after a 8-week resistance training for all training groups (P < 
0.05). The PII and PIII groups showed significant improvements rather than baseline in the thigh 
SSci email for contribution: editor@SSCI.org.uk 
International Journal of Sports Science and Engineering, 5 (2011) 2, pp 112-118 115
 
circumference (P < 0.05). Whereas, The PI and PIII groups showed significantly increases rather than 
baseline in the arm circumference (P < 0.05). In the bench press and leg press endurance, all training groups 
increased significantly from corresponding pre training and control group (except bench press endurance for 
PI group) (P < 0.05). There were no significant differences among groups at pre and post training for the all 
variables (P > 0.05). 
 
 
 
 
Fig 1. Differences in weight, percent body fat, arm and thigh circumference, one repetition maximum (1RM) at leg and 
bench press, and leg and bench press endurance (mean ± SD). 
* Significant difference from corresponding pre-training 
† Significant difference from corresponding CG 
PI; part I, PII; part II, PIII; part III, CG; control group 
4. Discussion 
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Hamid Arazi, et al: Effects of 8 Weeks Equal-Volume Resistance Training with Different Workout Frequency 116
The purpose of the present study was to compare the effect of three equal-volume resistance training 
programs on physiological abilities in novice subjects. We hypothesized that, resistance training for 3 days 
are better than 1 or 2 days. The main finding of the present study was that, there were no significant 
differences among groups on 1RM bench and leg press, and leg and bench press endurance. Also, the PIII 
and PII groups showed significant improvements than pre training on arm circumference, and PIII and PI 
groups indicated significant increases from corresponding pre values on thigh circumference. 
Upper and lower body strength increased significantly in all groups after a 8-week resistance training. In 
the contrast of our study, Berger (18) compared of one, two, and three sessions per week training the bench 
press or squat concluded that three sessions were superior to one or two sessions in bringing about strength 
increases. Another comparison of training frequency for the bench press also concluded that three sessions 
were superior to one or two sessions (19). The findings of the percent study are in line with Graves et al. (20) 
who reported that one session was equally as effective as two or three sessions per week when training for 
isolated lumbar extension strength. DeMichele et al. (21) found that two sessions per week was equivalent to 
three and superior to one session per week when training for torso rotation. These studies indicate that three 
sessions per week are superior to one or two sessions per week when training arm and leg musculature, 
whereas when training spine muscles, one or two sessions per week result in equivalent gains compared to 
three sessions per week. The training frequency of three sessions per week when training the arms and legs 
results in a 20 to 30% greater strength gain than a frequency of two sessions per week (22). Rhea et al. (23) 
determined the dose-response for strength development, reporting that untrained individuals see a consistent 
response as the training frequency increases up to 3 days/week. Strength coach and athletes believe that split 
routines allow individuals to train at a maximal effort level for given intensity, producing higher muscle 
strain on a specific session. These routines would facilitate recovery due to the alternation in the muscle 
group trained. But, it appears that split
training routine were not more effective than whole body training 
routines used by other, irrespectively of the training status (24,25). 
Only the PIII training group significantly increased in the arm and thigh circumference, whereas the PI 
and PII training groups increased either arm circumference or thigh circumference. All of the subjects 
improved their body weight and percent body fat (except CG). Increases in thigh CSA were only observed 
for the total body groups in the kraemer's et al study (13). Hakkkinen et al. (11) reported greater increases in 
muscle CSA when training volume was divided into two sessions per day rather than one. Huffman et al. (26) 
examined the effects of 10 weeks varying self-selected training frequencies among collegiate football players 
using different body-part training programs, and reported significant changes in the chest and thigh 
circumference, and sum of skinfold following four or five session-per-week training. Previous study reported 
increases in lean tissue mass after 10 weeks of training (27). Changes in muscle mass and CSA can be 
increases in; myofilaments, actin and myosin filaments, sarcoplasm, and connective tissue (28). A 
comparison of total body training routine and split system routine in young women who were previously not 
weight trained demonstrated no significant differences between groups in fat-free mass, or percent body fat 
changes (29). The results indicated that total-body and split-routine systems using the same total training 
volume produce similar results in healthy young women (29). Additionally, Carroll et al. (30) reported that 
when resistance training was equated for both time and number of sessions, 2 days/week resulted in a 
significant increase in the proportion of myosin heavy chain IIa compared with 3 days/week. The rest period 
between sessions must be sufficient to allow for muscular recuperation and development while alleviating 
the potential for overtraining (31). Split routine can allow performance of more assistance exercises and so 
many also be useful for enhancing physiological development. 
All experimental groups improved significantly rather than pre training and control group in leg and 
bench press endurance (except bench press endurance for the PI group). Kraemer et al. (12) compared the 
effects of total-body and upper-body resistance training on endurance performance, and reported similar 
improvements in the squat endurance, push-ups, and sit-ups. A split routine system allows the training 
intensity for a particular body part or group of exercises to be higher than would be possible if the four to six 
sessions were combined into two or three long sessions of equivalent training volume. It is also possible to 
develop split routines in which the total training volume per body part is higher than that in a typical total 
body training session because in a split routine each training session is dedicated to a smaller number of 
body parts or muscle groups (5). In the present study, we not found any significant changes among groups, 
but part III showed minimal improvement rather than other groups. We think that, the lack of change in the 
anthropometric profiles suggests that neural factors may have been more important to the observed increases 
in strength and endurance than morphological adaptations. Moritani and DeVries (32) described that neural 
SSci email for contribution: editor@SSCI.org.uk 
International Journal of Sports Science and Engineering, 5 (2011) 2, pp 112-118 117
 
adaptations would occur during the first weeks of training, it has been suggested that strength increments due 
to neural adaptations should also occur in highly trained athletes (33). Collectively, we recommend that, 
novice individuals had better use the split routine training for improving performance and promoting 
muscular adaptations. 
5. Acknowledgments 
The authors wish to thanks all the subjects for their participation and commitment to the study. 
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Treinamento de Contra Resistência - Hipertrofia, Quebra de Paradigmas, Saúde, Eletromiografias e Biomecânica/TREINAMENTO RESISTIDO PARA SAÚDE E PERFORMANCE.pdf
Resistance Training for 
Health and Performance
William J. Kraemer, PhD, Nicholas A. Ratamess, MS, and Duncan N. French, MS
Address
The Human Performance Laboratory, Department of Kinesiology, Unit 
1110, The University of Connecticut, Storrs, CT 06269-1110, USA. 
E-mail: kraemer@uconnvm.uconn.edu
Current Sports Medicine Reports 2002, 1:165–171
Current Science Inc. ISSN 1537-890x
Copyright © 2002 by Current Science Inc.
Introduction
Traditionally, strength athletes seeking to improve muscle
strength, hypertrophy, power, and sports-specific fitness
almost exclusively performed resistance training. Although
it has been shown to have profound effects on these
physical fitness components, only recently have the health-
related benefits of resistance training been elucidated. It is
now a popular form of exercise that is recommended by
national health organizations such as the American
College of Sports Medicine (ACSM), American Heart
Association, and the American Association for Cardiovas-
cular and Pulmonary Rehabilitation, in conjunction with
other modalities of exercise (ie, aerobic, flexibility), for the
maintenance and improvement of health and performance
[1••,2]. Particularly when incorporated into a comprehen-
sive fitness program, resistance training reduces several
risk factors associated with many diseases and physical
ailments, and improves the quality of life by preserving
and improving functional capacity [2]. In addition, it can
improve athletic performance by increasing muscular
strength, power, speed, size, endurance, balance, and
coordination [3••]. The vast body of literature examining
resistance training supports its inclusion into the daily
exercise regimens of the adolescent, adult, and elderly
populations. However, it is important that each individual
participating in a resistance training program has adequate
understanding of fundamental principles and techniques,
and in certain cases be supervised by qualified profession-
als (eg, inexperienced trainees, children) for the prevention
of injury and for maximizing the associated benefits [4•].
Important Qualities of 
Resistance Training Programs
In order to maximize the benefits of resistance training,
adherence to three basic principles is mandatory. These
principles are 1) progressive overload, 2) specificity, and 3)
variation. Progressive overload is the gradual increase of
stress placed on the body during resistance training. In
reality, resistance training is only effective for improving
health and performance if the human body is continually
required to exert a greater magnitude of force to meet
higher physiologic demands. Thus, a gradual increase in
demand of the resistance training program is necessary for
long-term improvement in muscular fitness and health.
Specificity refers to the body’s responses and subsequent
adaptations to certain program variables. The physiologic
adaptations to resistance training are specific to the muscle
actions involved [5], velocity of movement [6], exercise
range of motion [7], muscle groups trained [2], energy
systems involved [2], and the intensity and volume of
training [8]. The most effective resistance training
programs are designed individually to bring about specific
adaptations. Variation is the systematic alteration of the
resistance training program over time to allow for the
training stimulus to remain optimal. It has been shown
that systematic program variation is most effective for
long-term progression [9].
How much resistance training can improve health and
performance depends on the individual’s genetic makeup,
program design and implementation, and training status
or level of fitness. The rate of performance enhancement
differs considerably between previously untrained and
Resistance training is recommended by national health 
organizations for incorporation into a comprehensive 
fitness program that includes aerobic and flexibility 
exercise. Its potential benefits on health and performance 
are numerous; it has been shown to reduce body fat, 
increase basal metabolic rate, decrease blood pressure and 
the cardiovascular demands to exercise, improve blood 
lipid profiles, glucose tolerance, and insulin sensitivity, 
increase muscle and connective tissue cross-sectional area, 
improve functional capacity, and relieve low back pain. Many 
improvements in physical function and athletic performance 
are associated with the increases in muscle strength, power, 
endurance, and hypertrophy observed during resistance 
training. The
key element to effective resistance training is 
supervision by a qualified professional and the proper 
prescription of the program variables. Proper program 
design, ie, that which uses progressive overload, variation, 
and specificity, is essential to maximize the benefits 
associated with resistance training.
166 Training
trained individuals, as trained individuals have shown
much slower rates of improvement [10]. These data
demonstrate the difficulty in improving with greater levels
of fitness, and stress the importance of a proper resistance
training program design in order to progress further. It is
important to note that progression is not always the major
goal. Once a certain level of fitness is attained, many
individuals tailor their programs to maintain that level. In
either scenario, training programs are designed accordingly
through proper manipulation of program variables.
The key quality to an individualized resistance training
program is the acute manipulation of program variables
targeting certain areas of muscular fitness. The program
variables are 1) intensity (or loading), 2) volume (the
number of sets and repetitions), 3) exercises selected, 4)
the order of the exercises, 5) rest intervals between sets, 6)
velocity of contraction, and 7) frequency. Altering one or
more of these variables significantly affects the acute
responses and subsequent physiologic adaptations to
resistance training. Recently, the ACSM published a
position stand on recommended progression models
during resistance training [1••]. This document provides
recommendations for novice, intermediate, and advanced
levels of training for specific improvements in muscular
strength, power, hypertrophy, endurance, and motor
performance. Although it is beyond the scope of this
article, we encourage readers to refer to this document
[1••] for more information.
Resistance Training and Health Improvements
The potential health benefits associated with resistance train-
ing have significant impact on the quality of life and func-
tional capacity of individuals of all ages. The safe and proper
prescription of resistance exercise has been shown to reduce
body fat and increase basal metabolic rate, decrease blood
pressure and cardiovascular demands to activity, improve
blood lipid profiles, improve glucose tolerance and insulin
sensitivity, attenuate muscle sarcopenia, reduce the risk of
osteoporosis and colon cancer, and maintain long-term
independence and functional capacity [2,11,12,13••]. These
benefits, as well as the performance-related benefits, have
been shown to improve the quality of life in the elderly and
clinical populations, such as those with low back pain,
osteoarthritis, cardiovascular disease, HIV, neuromuscular
disease (eg, myasthenia gravis, myotonic dystrophy), obesity,
renal failure, chronic obstructive pulmonary disease, and
type 2 diabetes mellitus, and those recovering from a stroke,
[13••,14–18]. Although research has clearly demonstrated
the value of resistance training for improving muscular
performance, the influence of resistance exercise on health
and physical well-being continues to be elucidated.
Resistance training and function in the elderly
Advancing age, particularly in sedentary individuals, is
associated with a number of changes detrimental to health
and performance. Sarcopenia, or the loss of skeletal muscle
with advancing age, results in a lower basal metabolic rate,
weakness, reduced activity levels, decreased bone mineral
density, and increased risk of falls or injury [11,18]. This
reduction in skeletal muscle mass can result in frailty and
physical disability, which contribute to escalating health
care costs. Resistance training is considered a promising
intervention for reversing the loss of muscle function and
deterioration of muscle structure that is associated with
sarcopenia. Increasing evidence now indicates that elderly
subjects respond favorably to weight training in a
qualitatively similar manner as younger individuals. For
example, in a study of physically frail 76- to 92-year-old
men and women, Yarasheski et al. [19] reported that
muscle protein synthesis was significantly greater follow-
ing 3 months of supervised weight training. Other studies
have shown that resistance training significantly increases
the mass and quality of skeletal muscle [18]. These
findings indicate that elderly individuals can respond
favorably to the increased contractile activity associated
with progressive resistance training.
Cross-sectional and longitudinal data indicate that
muscle strength declines by approximately 15% per decade
in the sixth and seventh decades of life, and by about 30%
thereafter [2], leading to reductions in the ability to
perform daily functions. Therefore, a resistance training
intervention may be warranted to minimize these
reductions in strength and performance in the elderly. A
number of studies have demonstrated substantial increases
in muscle strength in the elderly following resistance
training [20,21]. For example, Charette et al. [20] reported
increases in strength of 28% to 115% following 12 weeks
of lower body resistance training in elderly women (mean
age = 70 years). Pertinent to daily function in the elderly,
other studies have shown significant improvements in
local muscular endurance, balance, coordination, and
functional ability (eg, ability to carry groceries, walk, and
climb stairs, reduced risk of falls, and so forth) [22]. These
studies indicate that resistance training can be performed
safely by the elderly, and that such exercise significantly
increases muscle strength and performance, due in part to
the mechanisms associated with muscle hypertrophy. Such
mechanisms serve to reverse the characteristic loss in lean
body mass that is associated with sarcopenia.
Body composition and weight loss
Obesity is a chronic metabolic disorder that is associated
with cardiovascular disease and increased morbidity and
mortality. Multiple epidemiologic studies now show an
association between body mass index and body fat with
coronary heart disease, type 2 diabetes and insulin resis-
tance, stroke, hypertension, and colon cancer [23]. The
mortality rate increases by 50% to 100% when body mass
index is equal to or greater than 30 kg/m2. Central obesity
appears to serve as a platform for a cascade of events that
can result in a variety of clinical health problems. Proper
Resistance Training for Health and Performance • Kraemer et al. 167
diet and aerobic exercise are important to weight loss and
body fat reductions. In addition, resistance training is
beneficial to body fat reduction and increase in lean
body mass.
A review of the literature has shown that body fat
reductions of 1% to 9% are possible following resistance
training programs of various durations [24]. Increases in
lean tissue mass and daily metabolic rates, in addition to
greater energy expenditure while exercising, are observed
during resistance training, which in turn may result in
body fat reductions [3••]. For example, Van Etten et al. [25]
reported a 9.5% increase in average daily metabolic rate
after 18 weeks of resistance training. High-volume work-
outs with short rest periods using a large muscle mass
appear most conducive to body fat reductions [3••].
Weight loss, and the associated dieresis, aid in reducing
blood pressure in both overweight hypertensive and
nonhypertensive individuals, reducing serum triglyceride
concentrations, increasing high-density lipoprotein (HDL)
cholesterol concentrations, and producing reductions in
low-density lipoprotein (LDL) cholesterol concentrations.
Blood pressure
Hypertension, defined as resting systolic or diastolic blood
pressure greater than or equal to 140/90 mm Hg, is a major
public health problem affecting approximately 24% of
noninstitutionalized adults in the United States [26].
Increasing scientific evidence now indicates that progres-
sive resistance training is an effective nonpharmacologic
intervention that

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