Muscle aging is associated with compromised Ca2+ spark signaling and segregated intracellular Ca2+ release

Weisleder, Noah; Brotto, Marco; Komazaki, Shinji; Pan, Zui; Zhao, Xiaoli; Nosek, Thomas M.; Parness, Jerome; Takeshima, Hiroshi; Ma, Jianjie

doi:10.1083/jcb.200604166

Cited by 123 publications

(144 citation statements)

References 38 publications

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“…Along with its binding partner, ADP/ATP translocase protein, which also shows marked increase in carbonylation with age, VDAC enables transport of ions, such as calcium ions (Ca +2 ), across the innermitochondrial membrane, critical to mitochondrial function (Pi et al, 2007). Impaired mitochondrial cycling of Ca +2 , has been associated with aging skeletal muscle (Weisleder et al, 2006). One may hypothesize that increased carbonyl modification of these proteins critical to mitochondrial inner membrane transport may contribute to this impaired cellular function in aged fast-twitch muscle.…”

Section: Carbonylation and Aging Skeletal Musclementioning

confidence: 99%

Age-related muscle dysfunction

Thompson

2009

Experimental Gerontology

200

170

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Aging is associated with a progressive decline of muscle mass, strength, and quality, a condition described as sarcopenia of aging. Despite the significance of skeletal muscle atrophy, the mechanisms responsible for the deterioration of muscle performance are only partially understood. The purpose of this review is to highlight cellular, molecular and biochemical changes that contribute to age-related muscle weakness. Keywordsactin; myosin; aged muscle; enzymatic activity; oxidative modifications SarcopeniaAging is associated with a progressive decline of muscle mass, strength, and quality, a condition described as sarcopenia. These age-related changes are observed in healthy, active adults who are 50 years and older (Hughes et al., 2002). The prevalence of sarcopenia in older adults under the age of 70 years is about 25% and increases to 40% in adults 80 years or older (Baumgartner et al., 1998). Sarcopenia represents a risk factor for frailty, loss of independence, and physical disability (Roubenoff, 2000). Loss of mobility resulting from muscle loss predicts major physical disability and mortality, and is associated with poor quality of life, social needs, and health care needs (Fried and Guralnik, 1997). The economic impact of sarcopenia and its detrimental correlates are immense (Janssen et al., 2004). Thus, understanding the mechanisms leading to muscle dysfunction (e.g., weakness) at advanced age represents a high public health priority. The purpose of this article is to highlight cellular, molecular, and biochemical changes that contribute to age-related muscle dysfunction. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Muscle physiology-short reviewFor skeletal muscle, the control of force has to be accurate and precise with the contractile machinery being switched on and off rapidly to allow for complex coordinated movements. Action potentials initiated at the neuromuscular junction propagate along the length of the fiber and the transverse tubules. As the wave of depolarization passes down the transverse tubules there is an interaction with the sarcoplasmic reticulum that results in the release of calcium, initiating the interaction of actin and myosin and muscle contraction. This process is known as excitation-contraction coupling. Thus, age-related structural changes or chemical modifications in proteins that affect excitation-contraction coupling are likely to influence muscle function.The basic contractile unit of muscle, the myofibril, consists of a linear array of sarcomeres, which contains interdigitating myosin and actin fila...

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Section: Carbonylation and Aging Skeletal Musclementioning

confidence: 99%

Age-related muscle dysfunction

Thompson

2009

Experimental Gerontology

200

170

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“…To test whether direct inhibition of mitochondrial Ca 2ϩ uniporter can affect the intracellular Ca 2ϩ release activity, Ru360 was applied to the G93A muscle fiber in which the Ca 2ϩ release events were first induced by osmotic shock. Osmotic stress-induced Ca 2ϩ activity has been previously established as an index for the integrity of the intracellular Ca 2ϩ release machinery of skeletal muscle cells (10,12,19,20).…”

Section: Inhibition Of the Mitochondrial Uniporter Promotes Propagatimentioning

confidence: 99%

Mitochondrial Calcium Uptake Regulates Rapid Calcium Transients in Skeletal Muscle during Excitation-Contraction (E-C) Coupling

Yan

et al. 2011

Journal of Biological Chemistry

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109

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Defective coupling between sarcoplasmic reticulum and mitochondria during control of intracellular Ca 2؉ signaling has been implicated in the progression of neuromuscular diseases. Our previous study showed that skeletal muscles derived from an amyotrophic lateral sclerosis (ALS) mouse model displayed segmental loss of mitochondrial function that was coupled with elevated and uncontrolled sarcoplasmic reticulum Ca 2؉ release activity. The localized mitochondrial defect in the ALS muscle allows for examination of the mitochondrial contribution to Ca 2؉ removal during excitation-contraction coupling by comparing Ca 2؉ transients in regions with normal and defective mitochondria in the same muscle fiber. Here we show that Ca 2؉ transients elicited by membrane depolarization in fiber segments with defective mitochondria display an ϳ10% increased amplitude. These regional differences in Ca 2؉ transients were abolished by the application of 1,2-bis(O-aminophenoxy)ethane-N,N,N,N-tetraacetic acid, a fast Ca 2؉ chelator that reduces mitochondrial Ca 2؉ uptake. Using a mitochondria-targeted Ca 2؉ biosensor (mt11-YC3.6) expressed in ALS muscle fibers, we monitored the dynamic change of mitochondrial Ca 2؉ levels during voltage-induced Ca 2؉ release and detected a reduced Ca 2؉ uptake by mitochondria in the fiber segment with defective mitochondria, which mirrored the elevated Ca 2؉ transients in the cytosol. Our study constitutes a direct demonstration of the importance of mitochondria in shaping the cytosolic Ca 2؉ signaling in skeletal muscle during excitation-contraction coupling and establishes that malfunction of this mechanism may contribute to neuromuscular degeneration in ALS.

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“…As Na + /K + pump has a crucial role in cell adaptation process, aging can be considered as a consequence of Na + /K + pump dysfunction [14,10], which leads to the down regulation Ca 2+ homeostasis [15][16][17][18]. Small enhancement of intracellular Ca 2+ concentration leads to the inactivation of Na…”

Section: Introductionmentioning

confidence: 99%

Age-Dependent Brain Tissue Hydration, Ca Exchange and their Dose- Dependent Ouabain Sensitivity

Ayrapetyan¹

2012

JBB

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Muscle aging is associated with compromised Ca2+ spark signaling and segregated intracellular Ca2+ release

Cited by 123 publications

References 38 publications

Age-related muscle dysfunction

Age-related muscle dysfunction

Mitochondrial Calcium Uptake Regulates Rapid Calcium Transients in Skeletal Muscle during Excitation-Contraction (E-C) Coupling

Age-Dependent Brain Tissue Hydration, Ca Exchange and their Dose- Dependent Ouabain Sensitivity

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