Progressive Disorganization of the Excitation-Contraction Coupling Apparatus in Aging Human Skeletal Muscle as Revealed by Electron Microscopy: A Possible Role in the Decline of Muscle Performance

Boncompagni, Simona; D’Amelio, L.; Fulle, Stefania; Fanò, Giorgio; Protasi, Feliciano

doi:10.1093/gerona/61.10.995

Cited by 80 publications

(89 citation statements)

References 61 publications

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“…We have already demonstrated that in adult muscle fibers of elderly there are alterations of CRU (Boncompagni et al, 2006). Sarcopenia is characterized by progressive denervation with loss of motor units (McNeil et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation

Pietrangelo¹,

Puglielli²,

Mancinelli³

et al. 2009

Experimental Gerontology

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ular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation. Experimental Gerontology, Elsevier, 2009, 44 (8) 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 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. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT AbstractSarcopenia is the age-related loss of muscle mass, strength and function. Human muscle proteins are synthesized at a slower rate in the elderly than in young adults, leading to atrophy and muscle mass loss with a decline in the functional capability. Additionally, aging is accompanied by a decrease in the ability of muscle tissue to regenerate following injury or overuse due to the impairment of intervening satellite cells, in which we previously reported oxidative damage evidences. The aim of the present study was to determine the effects of aging on myoblasts and myotubes obtained from human skeletal muscle, and characterize the transcriptional profile as molecular expression patterns in relation to age-dependent modifications in their regenerative capacity. Our data show that the failure to differentiate does not depend on reduced myogenic cell number, but difficulty to complete the differentiation program. Data reported here suggested the following findings: i) oxidative damage accumulation in molecular substrates, probably due to impaired antioxidant activity and insufficient repair capability, ii) limited capability of elderly myoblasts to execute a complete differentiation program; restricted fusion, possibly due to altered cytoskeleton turnover and extracellular matrix degradation, and iii) activation of atrophy mechanism by activation of a specific FOXO-dependent program.

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Section: Discussionmentioning

confidence: 99%

Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation

Pietrangelo¹,

Puglielli²,

Mancinelli³

et al. 2009

Experimental Gerontology

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“…In contrast with the tubular aggregates, the extent of these defects correspond with the size of the uncoupled Ca 2+ pool in a given muscle type. Additionally, electron microscopy studies of aged human muscle revealed similar disruptions of the triad junctions, but not an increased presence of large tubular aggregates (Boncompagni et al, 2006). Thus, it is likely that one factor contributing to the compromised Ca 2+ spark signaling in aged skeletal muscle may originate from the disruption of the connection between the t-tubule and SR membrane surfaces.…”

Section: Alteration Of Intracellular Membrane Ultrastructure During Mmentioning

confidence: 92%

“…Interestingly, some of these ultrastructural defects were also observed in aged wild type muscle, raising the possibility that defective membrane integrity or membrane cross-talk may be partially responsible for defects associated with aging (Boncompagni et al, 2006;Weisleder et al, 2006).…”

Section: Mg29 As a Marker Of Age-related Dysfunction In Skeletal Musclementioning

confidence: 99%

Altered Ca2+ sparks in aging skeletal and cardiac muscle

Weisleder

2008

Ageing Research Reviews

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Ca 2+ sparks are the fundamental units that comprise Ca 2+ -induced Ca 2+ release (CICR) in striated muscle cells. In cardiac muscle, spontaneous Ca 2+ sparks underlie the rhythmic CICR activity during heart contraction. In skeletal muscle, Ca 2+ sparks remain quiescent during the resting state and are activated in a plastic fashion to accommodate various levels of stress. With aging, the plastic Ca 2+ spark signal becomes static in skeletal muscle, whereas loss of CICR control leads to leaky Ca 2+ spark activity in aged cardiomyocytes. Ca 2+ spark responses reflect the integrated function of the intracellular Ca 2+ regulatory machinery centered around the triad or dyad junctional complexes of striated muscles, which harbor the principal molecular players of excitation-contraction coupling. This review highlights the contribution of age-related modification of the Ca 2+ release machinery and the effect of membrane structure and membrane cross-talk on the altered Ca 2+ spark signaling during aging of striated muscles.

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“…7 Some peculiar features allowed us to clearly distinguish large striated fibers in our patients from fibers of controls. 25 The myofibrillar apparatus, while quite well preserved, is in general less ordered than in normal muscle (Figure 5c, black arrows). In addition, large and abnormal areas filled with glycogen granules, mitochondria and vesicles were also frequent (Figures 5c and 6a, empty arrows).…”

Section: Force Measurementmentioning

confidence: 96%

“…[23][24][25] The contractile apparatus, formed by long cylinders called myofibrils, is formed by basic elements, the sarcomeres, which are delimited by Z lines (Figure 5a, black arrows). Sarcomeres of adjacent myofibrils are usually quite well aligned, forming the dark-pale cross striation that characterizes skeletal muscle.…”

Section: Force Measurementmentioning

confidence: 99%

Stable muscle atrophy in long-term paraplegics with complete upper motor neuron lesion from 3- to 20-year SCI

et al. 2007

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Study design: Unrandomized trial. Objectives: To investigate the structural and functional relationships and the progression of muscle atrophy up to 20 years of spastic paraplegia. Setting: Clinical follow-up in Vienna, Austria; muscle biopsies analyzed by light microscopy in Padova and by electron microscopy (EM) in Chieti, Italy. Methods: Force was measured as knee extension torque; trophism by computer tomography scan; tissue composition and fiber morphology by histopathology and EM. Results: In the long-term group of patients (17.0 ± 2.6 years), force and size of thigh muscles were only slightly different from those of mid-term subjects (2.2 ± 0.5 years). Histology and ultrastructure confirm that the difference in average size of muscle fibers between long-term and mid-term paralyzed leg muscles is actually very small. In addition, muscle fibers maintain the striated appearance characteristic of normal skeletal fibers even after 14-20 years of paralysis. Ultrastructural alterations of the activating and metabolic machineries, and the presence of fibers with lower motor neuron denervation features, may explain the low-force output and the reduced endurance of paretic muscles. Conclusion: The stable muscle atrophy that characterizes long-lasting spastic paraplegia suggests that there are no upper-time limits to begin a training program based on functional electrical stimulation.

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Progressive Disorganization of the Excitation-Contraction Coupling Apparatus in Aging Human Skeletal Muscle as Revealed by Electron Microscopy: A Possible Role in the Decline of Muscle Performance

Cited by 80 publications

References 61 publications

Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation

Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation

Altered Ca2+ sparks in aging skeletal and cardiac muscle

Stable muscle atrophy in long-term paraplegics with complete upper motor neuron lesion from 3- to 20-year SCI

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