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      Evolving concepts on the age-related changes in “muscle quality”

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          Abstract

          The deterioration of skeletal muscle with advancing age has long been anecdotally recognized and has been of scientific interest for more than 150 years. Over the past several decades, the scientific and medical communities have recognized that skeletal muscle dysfunction (e.g., muscle weakness, poor muscle coordination, etc.) is a debilitating and life-threatening condition in the elderly. For example, the age-associated loss of muscle strength is highly associated with both mortality and physical disability. It is well-accepted that voluntary muscle force production is not solely dependent upon muscle size, but rather results from a combination of neurologic and skeletal muscle factors, and that biologic properties of both of these systems are altered with aging. Accordingly, numerous scientists and clinicians have used the term “muscle quality” to describe the relationship between voluntary muscle strength and muscle size. In this review article, we discuss the age-associated changes in the neuromuscular system—starting at the level of the brain and proceeding down to the subcellular level of individual muscle fibers—that are potentially influential in the etiology of dynapenia (age-related loss of muscle strength and power).

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          Most cited references206

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          The cholinergic hypothesis of geriatric memory dysfunction.

          Biochemical, electrophysiological, and pharmacological evidence supporting a role for cholinergic dysfunction in age-related memory disturbances is critically reviewed. An attempt has been made to identify pseudoissues, resolve certain controversies, and clarify misconceptions that have occurred in the literature. Significant cholinergic dysfunctions occur in the aged and demented central nervous system, relationships between these changes and loss of memory exist, similar memory deficits can be artificially induced by blocking cholinergic mechanisms in young subjects, and under certain tightly controlled conditions reliable memory improvements in aged subjects can be achieved after cholinergic stimulation. Conventional attempts to reduce memory impairments in clinical trials hav not been therapeutically successful, however. Possible explanations for these disappointments are given and directions for future laboratory and clinical studies are suggested.
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            Calcium signaling

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              Ryanodine receptor oxidation causes intracellular calcium leak and muscle weakness in aging.

              Age-related loss of muscle mass and force (sarcopenia) contributes to disability and increased mortality. Ryanodine receptor 1 (RyR1) is the skeletal muscle sarcoplasmic reticulum calcium release channel required for muscle contraction. RyR1 from aged (24 months) rodents was oxidized, cysteine-nitrosylated, and depleted of the channel-stabilizing subunit calstabin1, compared to RyR1 from younger (3-6 months) adults. This RyR1 channel complex remodeling resulted in "leaky" channels with increased open probability, leading to intracellular calcium leak in skeletal muscle. Similarly, 6-month-old mice harboring leaky RyR1-S2844D mutant channels exhibited skeletal muscle defects comparable to 24-month-old wild-type mice. Treating aged mice with S107 stabilized binding of calstabin1 to RyR1, reduced intracellular calcium leak, decreased reactive oxygen species (ROS), and enhanced tetanic Ca(2+) release, muscle-specific force, and exercise capacity. Taken together, these data indicate that leaky RyR1 contributes to age-related loss of muscle function. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                russd@ohio.edu
                clarkb2@ohio.edu
                Journal
                J Cachexia Sarcopenia Muscle
                J Cachexia Sarcopenia Muscle
                Journal of Cachexia, Sarcopenia and Muscle
                Springer-Verlag (Berlin/Heidelberg )
                2190-5991
                2190-6009
                3 February 2012
                3 February 2012
                June 2012
                : 3
                : 2
                : 95-109
                Affiliations
                [ ]Ohio Musculoskeletal and Neurological Institute (OMNI), Ohio University, 236 Irvine Hall, Athens, OH 45701 USA
                [ ]Division of Physical Therapy, School of Rehabilitation and Communication Sciences, Ohio University, Grover Center W279, Athens, OH 45701 USA
                [ ]Department of Biomedical Sciences, Ohio University, 236 Irvine Hall, Athens, OH 45701 USA
                Article
                54
                10.1007/s13539-011-0054-2
                3374023
                22476917
                f0343df9-6aee-408d-982e-3b4f04a2fe50
                © The Author(s) 2012
                History
                : 9 September 2011
                : 26 December 2011
                Categories
                Review
                Custom metadata
                © Springer-Verlag 2012

                Orthopedics
                muscle,aging,strength,weakness,sarcopenia,dynapenia
                Orthopedics
                muscle, aging, strength, weakness, sarcopenia, dynapenia

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