Myofilament Protein Alterations Promote Physical Disability in Aging and Disease

Miller, Mark S.; Toth, Michael J.

doi:10.1097/jes.0b013e31828bbcd8

Cited by 32 publications

(24 citation statements)

References 34 publications

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“…Specific to this point, the development of fatigue in the young and old was similar during the isometric task. This finding confirms accumulating evidence suggesting an age‐related preservation, or even improvement, in fatigue resistance during isometric tasks, possibly occurring as a result of slowed contractile properties and greater myofilament stiffness leading to greater force generation during isometric contractions (Miller & Toth, ). However, unique to the study by Rudroff et al .…”

supporting

confidence: 89%

Heterogeneity of blood flow: impact of age on muscle specific tissue perfusion during exercise

Trinity

Layec

Lee

2014

The Journal of Physiology

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supporting

confidence: 89%

Heterogeneity of blood flow: impact of age on muscle specific tissue perfusion during exercise

Trinity

Layec

Lee

2014

The Journal of Physiology

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“…2016), and/or impaired cross‐bridge mechanics and Ca 2+ handling (Frontera et al . 2000; Miller & Toth, ; Lamboley et al . 2015; Lamboley et al .…”

Section: Discussionmentioning

confidence: 99%

Effects of elevated H⁺ and P_i on the contractile mechanics of skeletal muscle fibres from young and old men: implications for muscle fatigue in humans

Sundberg

Hunter

Trappe

et al. 2018

The Journal of Physiology

105

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The present study aimed to identify the mechanisms responsible for the loss in muscle power and increased fatigability with ageing by integrating measures of whole-muscle function with single fibre contractile mechanics. After adjusting for the 22% smaller muscle mass in old (73-89 years, n = 6) compared to young men (20-29 years, n = 6), isometric torque and power output of the knee extensors were, respectively, 38% and 53% lower with age. Fatigability was ∼2.7-fold greater with age and strongly associated with reductions in the electrically-evoked contractile properties. To test whether cross-bridge mechanisms could explain age-related decrements in knee extensor function, we exposed myofibres (n = 254) from the vastus lateralis to conditions mimicking quiescent muscle and fatiguing levels of acidosis (H ) (pH 6.2) and inorganic phosphate (P ) (30 mm). The fatigue-mimicking condition caused marked reductions in force, shortening velocity and power and inhibited the low- to high-force state of the cross-bridge cycle, confirming findings from non-human studies that these ions act synergistically to impair cross-bridge function. Other than severe age-related atrophy of fast fibres (-55%), contractile function and the depressive effects of the fatigue-mimicking condition did not differ in fibres from young and old men. The selective loss of fast myosin heavy chain II muscle was strongly associated with the age-related decrease in isometric torque (r = 0.785) and power (r = 0.861). These data suggest that the age-related loss in muscle strength and power are primarily determined by the atrophy of fast fibres, but the age-related increased fatigability cannot be explained by an increased sensitivity of the cross-bridge to H and P .

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“…For example, after 3 weeks of hindlimb unloading, levels of contractile proteins decreased by 40–70 %, and the ratio of actin/myosin filaments decreased by 31 % [8]. Reduction in muscle quality caused by alterations in myofilament contractile proteins (myosin and actin) may scale up from the molecular to the single fiber and tissue level to impact muscle performance [29]. Thus, up-regulation of myosin-2 is one of the most important mechanisms to maintain the integrity of the SOL muscle fiber in the 60-d hibernation ground squirrels.…”

Section: Discussionmentioning

confidence: 99%

iTRAQ-based proteomic analysis of myofibrillar contents and relevant synthesis and proteolytic proteins in soleus muscle of hibernating Daurian ground squirrels (Spermophilus dauricus)

et al. 2016

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BackgroundDaurian ground squirrels (Spermophilus dauricus) deviate from significant increase of protein catabolism and loss of myofibrillar contents during long period of hibernation inactivity.MethodsHere we use iTRAQ based quantitative analysis to examine proteomic changes in the soleus of squirrels in pre-hibernation, hibernation and post-hibernation states. The total proteolysis rate of soleus was measured by the release of the essential amino acid tyrosine from isolated muscles. Immunofluorescent analysis was used to determine muscle fiber cross-sectional area. Western blot was used for the validation of the quantitative proteomic analysis.ResultsThe proteomic responses to hibernation had a 0.4- to 0.8-fold decrease in the myofibrillar contractile protein levels of myosin-3, myosin-13 and actin, but a 2.1-fold increase in myosin-2 compared to pre-hibernation group. Regulatory proteins such as troponin C and tropomodulin-1 were 1.4-fold up-regulated and 0.7-fold down-regulated, respectively, in hibernation compared to pre-hibernation group. Moreover, 10 proteins with proteolytic function in hibernation, which was less than 14 proteins in the post-hibernation group, were up-regulated relative to the pre-hibernation group. The total proteolysis rates of soleus in hibernation and post-hibernation groups were significantly inhibited as compared with pre-hibernation group.ConclusionThese findings suggest that the myofibrillar remodeling and partial suppression of myofibrillar proteolysis were likely responsible for preventing skeletal muscle atrophy during prolonged disuse in hibernation. This is the first study where the myofibrillar contents and relevant synthesis and proteolytic proteins in slow soleus was discussed based on proteomic investigation performed on wild Daurian ground squirrels. Our results lay the foundation for further research in preventing disuse-induced skeletal muscle atrophy in mammals.Electronic supplementary materialThe online version of this article (doi:10.1186/s12953-016-0105-x) contains supplementary material, which is available to authorized users.

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Myofilament Protein Alterations Promote Physical Disability in Aging and Disease

Cited by 32 publications

References 34 publications

Heterogeneity of blood flow: impact of age on muscle specific tissue perfusion during exercise

Heterogeneity of blood flow: impact of age on muscle specific tissue perfusion during exercise

Effects of elevated H⁺ and P_i on the contractile mechanics of skeletal muscle fibres from young and old men: implications for muscle fatigue in humans

iTRAQ-based proteomic analysis of myofibrillar contents and relevant synthesis and proteolytic proteins in soleus muscle of hibernating Daurian ground squirrels (Spermophilus dauricus)

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Myofilament Protein Alterations Promote Physical Disability in Aging and Disease

Cited by 32 publications

References 34 publications

Heterogeneity of blood flow: impact of age on muscle specific tissue perfusion during exercise

Heterogeneity of blood flow: impact of age on muscle specific tissue perfusion during exercise

Effects of elevated H+ and Pi on the contractile mechanics of skeletal muscle fibres from young and old men: implications for muscle fatigue in humans

iTRAQ-based proteomic analysis of myofibrillar contents and relevant synthesis and proteolytic proteins in soleus muscle of hibernating Daurian ground squirrels (Spermophilus dauricus)

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Effects of elevated H⁺ and P_i on the contractile mechanics of skeletal muscle fibres from young and old men: implications for muscle fatigue in humans