Muscle Quality in Skeletal Muscle Function Deficit: Recent Advances and Potential Clinical and Therapeutic Implications

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Background

While current consensus-driven sarcopenia staging algorithms relates loss of muscle strength, loss of muscle mass, and diminished functioning, the larger concept of age-related Skeletal Muscle Function Deficit (SMFD) needs to incorporate muscle quality and metabolic health. A growing body of evidence indicates that factors underpinning muscle quality play a critical role in decreased muscle function, impaired mobility and metabolic dysfunction in older adults. Changes in muscle composition based on myosteatosis (excessive levels of inter and intramuscular adipose tissue and intramyocellular lipids) adversely affect metabolism and peak muscle force generation, and are further associated with a multitude of other negative outcomes. The need remains to reach a consensus on standardized approaches to assessing the aspects of muscle quality that influence major muscle functions and contribute to SMFD. These methods need to allow for the rapid assessment of muscle tissue composition in multiple clinical setting with minimal patient burden.

Garnering consensus on the major domains of muscle quality, and measurement methods suitable for a variety of clinical settings may help advance knowledge of SMFD and identify individuals who would benefit from interventions directed at improving muscle quality. The major goal of this Research Topic is to gather manuscripts with the latest information including, but not limited to, the following existent research gap areas:
1) Measured approach(es) to scaling factors regarding timed tests of performance and force production that add value to the clinical assessment of SMFD and the monitoring of patient status following exercise-based interventions and other forms of treatment.
2) Clinically feasible imaging assessment tools to reliably evaluate muscle quality in a variety of settings. New validation studies remain essential to move toward a wider adoption of alternate imaging methods.
3) Features of skeletal muscle related to tissue characteristics that aid the sarcopenia and SMFD diagnosis including discriminating between patient groups, predicting incidence of metabolic disorders or disablement.
4) New evidence on other biologic causative factors including reactive oxygen species (ROS) known to closely relate to muscle aging and to negatively impact muscle quality.
5) As therapies for preserving muscle mass, such as myostatin inhibitors and irisin-activating compounds, are already in development there is a need for studies focusing on biological determinants of myosteatosis and muscle quality which may have a potential therapeutic implications.
6) Determine the magnitudes and significance of the associations between lifestyle risk factors such as objective measures of physical activity and sedentary behavior with muscle quality and myosteatosis, particularly among older adults.

Other specific studies on muscle quality particularly related to myosteatosis' in aging muscles and metabolic disease include:
1) Standardized definition and imaging tools and measurement of myosteatosis applicable across studies/populations that can enhance clinical translation of findings.
2) Best practices for the method of acquisition for cross-sectional and longitudinal studies, data acquisition and analysis using the same cutpoints nomenclature, followed by cross-talk between imaging modalities to ensure that what is being assessed, for example, from CTs is the same being assessed with MRIs.
3) Bridging molecular, pathologic, and population studies to identify what is being examined in the tissue and promote a better understanding of the risk factors and mechanisms for myosteatosis, and whether the condition is reversible and to what extent.
4) Longer longitudinal cohorts examining a variety of muscles across sex/gender and racial/ethnic groups, and disease populations. Identification of which muscles should be examined and measured (how), as well as the establishment of widely accepted cutpoints will enhance clinical practice toward identification of individuals at risk for poor outcomes.
5) Multidisciplinary collaborations examining the combination of diet, physical activity, and medications essential to manage individuals at risk. Combined examination of interventions will likely result in more useful information/provide new treatment options.
6) Investigation into the commonality between myosteatosis and changes that occur in other cells in the body may also lead to new discoveries and treatments options.
7) Myosteatosis role as a newly defined independent risk factor.

This Research Topic calls for submissions of manuscripts primarily from original studies focusing on the biology, epidemiology, clinical and interventional research that documents advances in knowledge of the role of muscle quality in aging-related SMFD. In addition to research gaps identified above, further sources of information on research gaps include but are not limited to:
1) The Need for Standardized Assessment of Muscle Quality in Skeletal Muscle Function Deficit and Other Aging-Related Muscle Dysfunctions: A Symposium Report
2) Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging

Research Topic Research topic image

Keywords: muscle quality, myosteatosis, sarcopenia, mobility-disability, skeletal muscle function deficit

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