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      Sarcopenia: etiology, clinical consequences, intervention, and assessment

      review-article

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          Abstract

          The aging process is associated with loss of muscle mass and strength and decline in physical functioning. The term sarcopenia is primarily defined as low level of muscle mass resulting from age-related muscle loss, but its definition is often broadened to include the underlying cellular processes involved in skeletal muscle loss as well as their clinical manifestations. The underlying cellular changes involve weakening of factors promoting muscle anabolism and increased expression of inflammatory factors and other agents which contribute to skeletal muscle catabolism. At the cellular level, these molecular processes are manifested in a loss of muscle fiber cross-sectional area, loss of innervation, and adaptive changes in the proportions of slow and fast motor units in muscle tissue. Ultimately, these alterations translate to bulk changes in muscle mass, strength, and function which lead to reduced physical performance, disability, increased risk of fall-related injury, and, often, frailty. In this review, we summarize current understanding of the mechanisms underlying sarcopenia and age-related changes in muscle tissue morphology and function. We also discuss the resulting long-term outcomes in terms of loss of function, which causes increased risk of musculoskeletal injuries and other morbidities, leading to frailty and loss of independence.

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          Most cited references180

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          The Loss of Skeletal Muscle Strength, Mass, and Quality in Older Adults: The Health, Aging and Body Composition Study

          The loss of muscle mass is considered to be a major determinant of strength loss in aging. However, large-scale longitudinal studies examining the association between the loss of mass and strength in older adults are lacking.
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            Bone "mass" and the "mechanostat": a proposal.

            H M Frost (1987)
            The observed fit of bone mass to a healthy animal's typical mechanical usage indicates some mechanism or mechanisms monitor that usage and control the three longitudinal growth, bone modeling, and BMU-based remodeling activities that directly determine bone mass. That mechanism could be named a mechanostat. Accumulated evidence suggests it includes the bone itself, plus mechanisms that transform its mechanical usage into appropriate signals, plus other mechanisms that detect those signals and then direct the above three biologic activities. In vivo studies have shown that bone strains in or above the 1500-3000 microstrain range cause bone modelling to increase cortical bone mass, while strains below the 100-300 microstrain range release BMU-based remodeling which then removes existing cortical-endosteal and trabecular bone. That arrangement provides a dual system in which bone modeling would adapt bone mass to gross overloading, while BMU-based remodeling would adapt bone mass to gross underloading, and the above strain ranges would be the approximate "setpoints" of those responses. The anatomical distribution of those mechanical usage effects are well known. If circulating agents or disease changed the effective setpoints of those responses their bone mass effects should copy the anatomical distribution of the mechanical usage effects. That seems to be the case for many agents and diseases, and several examples are discussed, including postmenopausal osteoporosis, fluoride effects, bone loss in orbit, and osteogenesis imperfecta. The mechanostat proposal is a seminal idea which fits diverse evidence but it requires critique and experimental study.
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              Notch-mediated restoration of regenerative potential to aged muscle.

              A hallmark of aging is diminished regenerative potential of tissues, but the mechanism of this decline is unknown. Analysis of injured muscle revealed that, with age, resident precursor cells (satellite cells) had a markedly impaired propensity to proliferate and to produce myoblasts necessary for muscle regeneration. This was due to insufficient up-regulation of the Notch ligand Delta and, thus, diminished activation of Notch in aged, regenerating muscle. Inhibition of Notch impaired regeneration of young muscle, whereas forced activation of Notch restored regenerative potential to old muscle. Thus, Notch signaling is a key determinant of muscle regenerative potential that declines with age.

                Author and article information

                Contributors
                +1-415-3534552 , +1-415-3539425 , thomas.lang@radiology.ucsf.edu
                Journal
                Osteoporos Int
                Osteoporosis International
                Springer-Verlag (London )
                0937-941X
                1433-2965
                25 September 2009
                25 September 2009
                April 2010
                : 21
                : 4
                : 543-559
                Affiliations
                [1 ]Department of Radiology and Biomedical Imaging, UCSF/UCB Joint Bioengineering Graduate Group, University of California, UCSF/Center for Molecular and Functional Imaging, 185 Berry Street, Suite 350, San Francisco, CA 94143-0946 USA
                [2 ]Department of Radiology and Biomedical Imaging, University of California, UCSF/Center for Molecular and Functional Imaging, 185 Berry Street, Suite 350, San Francisco, CA 94143-0946 USA
                [3 ]California Pacific Medical Center Research Institute, San Francisco, CA USA
                [4 ]Physiology and Biophysics, University of California, Irvine, CA USA
                [5 ]School of Human Movement Studies, The University of Queensland, Brisbane, Australia
                [6 ]Laboratory of Epidemiology and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD USA
                Article
                1059
                10.1007/s00198-009-1059-y
                2832869
                19779761
                acbcd83b-9a9c-4cdc-9f99-7ee3c38a8a72
                © The Author(s) 2009
                History
                : 25 April 2009
                : 18 August 2009
                Categories
                Review
                Custom metadata
                © International Osteoporosis Foundation and National Osteoporosis Foundation 2010

                Orthopedics
                imaging,aging,sarcopenia,falls,skeletal muscle,muscle strength
                Orthopedics
                imaging, aging, sarcopenia, falls, skeletal muscle, muscle strength

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