scholarly journals Protection From Contraction-Induced Injury Provided to Skeletal Muscles of Young and Old Mice by Passive Stretch Is Not Due to a Decrease in Initial Mechanical Damage

2006 ◽  
Vol 61 (6) ◽  
pp. 527-533 ◽  
Author(s):  
N. C. Lockhart ◽  
S. V. Brooks
2005 ◽  
Vol 98 (4) ◽  
pp. 1562-1566 ◽  
Author(s):  
Troy A. Hornberger ◽  
R. D. Mateja ◽  
E. R. Chin ◽  
J. L. Andrews ◽  
K. A. Esser

The capacity for skeletal muscle to recover its mass following periods of unloading (regrowth) has been reported to decline with age. Although the mechanisms responsible for the impaired regrowth are not known, it has been suggested that aged muscles have a diminished capacity to sense and subsequently respond to a given amount of mechanical stimuli (mechanosensitivity). To test this hypothesis, extensor digitorum longus muscles from young (2–3 mo) and old (26–27 mo) mice were subjected to intermittent 15% passive stretch (ex vivo) as a source of mechanical stimulation and analyzed for alterations in the phosphorylation of stress-activated protein kinase (p38), ribosomal S6 kinase (p70S6k), and the p54 jun N-terminal kinase (JNK2). The results indicated that the average magnitude of specific tension (mechanical stimuli) induced by 15% stretch was similar in muscles from young and old mice. Young and old muscles also revealed similar increases in the magnitude of mechanically induced p38, p70S6k (threonine/serine 421/424 and threonine 389), and JNK2 phosphorylation. In addition, coincubation experiments demonstrated that the release of locally acting growth factors was not sufficient for the induction of JNK2 phosphorylation, suggesting that JNK2 was activated by a mechanical rather than a mechanical/growth factor-dependent mechanism. Taken together, the results of this study demonstrate that aging does not alter the mechanosensitivity of the p38, p70S6k, and JNK2 signaling pathways in skeletal muscle.


2015 ◽  
Vol 308 (2) ◽  
pp. C123-C138 ◽  
Author(s):  
E. Giacomello ◽  
M. Quarta ◽  
C. Paolini ◽  
R. Squecco ◽  
P. Fusco ◽  
...  

Muscle-specific ankyrins 1 (sAnk1) are a group of small ankyrin 1 isoforms, of which sAnk1.5 is the most abundant. sAnk1 are localized in the sarcoplasmic reticulum (SR) membrane from where they interact with obscurin, a myofibrillar protein. This interaction appears to contribute to stabilize the SR close to the myofibrils. Here we report the structural and functional characterization of skeletal muscles from sAnk1 knockout mice (KO). Deletion of sAnk1 did not change the expression and localization of SR proteins in 4- to 6-mo-old sAnk1 KO mice. Structurally, the main modification observed in skeletal muscles of adult sAnk1 KO mice (4–6 mo of age) was the reduction of SR volume at the sarcomere A band level. With increasing age (at 12–15 mo of age) extensor digitorum longus (EDL) skeletal muscles of sAnk1 KO mice develop prematurely large tubular aggregates, whereas diaphragm undergoes significant structural damage. Parallel functional studies revealed specific changes in the contractile performance of muscles from sAnk1 KO mice and a reduced exercise tolerance in an endurance test on treadmill compared with control mice. Moreover, reduced Qγcharge and L-type Ca2+current, which are indexes of affected excitation-contraction coupling, were observed in diaphragm fibers from 12- to 15-mo-old mice, but not in other skeletal muscles from sAnk1 KO mice. Altogether, these findings show that the ablation of sAnk1, by altering the organization of the SR, renders skeletal muscles susceptible to undergo structural and functional alterations more evident with age, and point to an important contribution of sAnk1 to the maintenance of the longitudinal SR architecture.


Author(s):  
А.А. Пальцын

Группа исследователей из Гарвардского университета в 2013 и последующих годах опубликовала серию статей об одном из трансформирующих факторов роста b - GDF-11. По данным этого коллектива, концентрация GDF-11 в крови и тканях млекопитающих с возрастом снижается. Искусственное повышение содержания GDF-11 у старых мышей путем ежедневных инъекций рекомбинантного GDF-11 или парабиоза в течение месяца с молодыми мышами существенно снижало и даже устраняло свойственные старости неблагоприятные изменения сердца, скелетных мышц, мозга. Статьи Гарвардской группы привлекли большое внимание научного сообщества, были комментированы в сотнях публикаций, и в них GDF-11 стали часто называть белком молодости. Капитальность заявки Гарварда стимулировала капитальность проверочных экспериментов с привлечением максимально надежных методик. Эти эксперименты расширили знания о GDF-11, но не подтвердили его права называться белком молодости. A research group at the Harvard University in 2013 and the next years has published a series of articles focusing on one of transforming growth factors b, GDF-11. According to these reports mammalian blood and tissue concentrations of GDF-11 decrease with age. Increasing the GDF-11 content in old mice using daily injections of recombinant GDF-11 or one-month parabiosis induced in young mice significantly reduced and even eliminated adverse, old age-specific changes in the heart, skeletal muscles, and brain. The reports of the Harvard group have attracted much attention of the scientific community, and were cited in hundreds of publications where GDF-11 was often called the protein of youth. The solidity of the Harvard team statement warranted solidity of test experiments, which used the most reliable methods. These experiments have expanded the knowledge of GDF-11 but did not confirm its right to be called a protein of youth.


2017 ◽  
Vol 313 (2) ◽  
pp. E222-E232 ◽  
Author(s):  
Marin Jane McBride ◽  
Kevin P. Foley ◽  
Donna M. D’Souza ◽  
Yujin E. Li ◽  
Trevor C. Lau ◽  
...  

The mechanisms underpinning decreased skeletal muscle strength and slowing of movement during aging are ill-defined. “Inflammaging,” increased inflammation with advancing age, may contribute to aspects of sarcopenia, but little is known about the participatory immune components. We discovered that aging was associated with increased caspase-1 activity in mouse skeletal muscle. We hypothesized that the caspase-1-containing NLRP3 inflammasome contributes to sarcopenia in mice. Male C57BL/6J wild-type (WT) and NLRP3−/− mice were aged to 10 (adult) and 24 mo (old). NLRP3−/− mice were protected from decreased muscle mass (relative to body mass) and decreased size of type IIB and IIA myofibers, which occurred between 10 and 24 mo of age in WT mice. Old NLRP3−/− mice also had increased relative muscle strength and endurance and were protected from age-related increases in the number of myopathic fibers. We found no evidence of age-related or NLRP3-dependent changes in markers of systemic inflammation. Increased caspase-1 activity was associated with GAPDH proteolysis and reduced GAPDH enzymatic activity in skeletal muscles from old WT mice. Aging did not alter caspase-1 activity, GAPDH proteolysis, or GAPDH activity in skeletal muscles of NLRP3−/− mice. Our results show that the NLRP3 inflammasome participates in age-related loss of muscle glycolytic potential. Deletion of NLRP3 mitigates both the decline in glycolytic myofiber size and the reduced activity of glycolytic enzymes in muscle during aging. We propose that the etiology of sarcopenia involves direct communication between immune responses and metabolic flux in skeletal muscle.


1989 ◽  
Vol 21 (Supplement) ◽  
pp. S28
Author(s):  
Y. Atomi ◽  
S. Yamada ◽  
H. Hatta ◽  
Y. Yamamoto ◽  
S. Shinohara

2006 ◽  
Vol 17 (6) ◽  
pp. 615-628 ◽  
Author(s):  
Arimantas Lionikas ◽  
David A. Blizard ◽  
David J. Vandenbergh ◽  
Joseph T. Stout ◽  
George P. Vogler ◽  
...  

2006 ◽  
Vol 100 (2) ◽  
pp. 656-661 ◽  
Author(s):  
Erik P. Rader ◽  
John A. Faulkner

With aging, the skeletal muscles of humans sustain decreases of ∼30% in mass and maximum force. Contraction-induced injury may contribute to these declines. When a 225 lengthening contraction protocol (LCP) was administered to small, non-weight-bearing muscles of mice, muscles of young/adult mice recovered completely, whereas those of old mice sustained permanent deficits of 20% in muscle mass and maximum force. Despite these observations, whether a large, frequently recruited, weight-bearing muscle sustains such permanent damage is not known. The hypothesis tested is that after a severe contraction-induced injury, large, weight-bearing muscles of old mice sustain permanent reductions in mass and force. The LCP was administered to plantar flexor muscles of adult and old, male C57BL/6 mice. At 3 days, 1 mo, and 2 mo after the LCP, maximum isometric forces were measured, anesthetized mice were euthanized, and muscles were removed and weighed. Two months after the LCP, the muscles of the adult mice regained control values of mass and force, whereas for muscles of old mice the mass decreased by 24% and the maximum force decreased by 32%. We conclude that a severe contraction-induced injury to large, weight-bearing muscles of old mice causes permanent deficits in mass and force.


Author(s):  
Francesca M. Alves ◽  
Kai Kysenius ◽  
Marissa K. Caldow ◽  
Justin P. Hardee ◽  
Peter J. Crouch ◽  
...  

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