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Cited by 468Nutrition and Health in AgingMuscle Physiology and DisordersAdipose Tissue and Metabolism

Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging

Open access
Correa-de-Araujo, Rosaly, Addison, Odessa, Miljkovic, Iva, Goodpaster, Bret H., Bergman, Bryan C., Clark, Richard V., Elena, Joanne W., Esser, Karyn A. +7 more·2020·Frontiers in Physiology
DOI 10.3389/fphys.2020.00963PMC PMC7438777
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Abstract

Skeletal muscle fat infiltration (known as myosteatosis) is an ectopic fat depot that increases with aging and is recognized to negatively correlate with muscle mass, strength and mobility, and disrupt metabolism (insulin resistance, diabetes). An interdisciplinary workshop convened by the National Institute on Aging Division of Geriatrics and Clinical Gerontology on September 2018, discussed myosteatosis in the context of Skeletal Muscle Function Deficit (SMFD). Its purpose was to gain a better understanding of the roles of myosteatosis in aging muscles and metabolic disease, particularly its potential determinants and clinical consequences, and ways of properly assessing it. Special attention was given to functional status and standardization of measures of body composition (including the value of D3- Creatine dilution method) and imaging approaches (including ways to better use Dual-Energy X-Ray Absorptiometry [DXA] through the Shape and Appearance Modeling) to assess lean mass, sarcopenia, and myosteatosis. The workshop convened innovative new areas of scientific relevance to light such as the effect of circadian rhythms and clock disruption in skeletal muscle structure, function, metabolism, and potential contribution to increased myosteatosis. A muscle-bone interaction perspective compared mechanisms associated with myosteatosis and bone marrow adiposity. Potential preventive and therapeutic approaches highlighted ongoing work on physical activity, myostatin treatment, and calorie restriction. Myosteatosis’ impact on cancer survivors raised new possibilities to identify its role and to engage in cross-disciplinary collaboration. A wide range of research opportunities and challenges in planning for the most appropriate study design, interpretation of findings, and consequent translation into clinical practice were discussed and are presented here.

AI snapshot

Written from the paper’s full text.

TL;DR

This National Institute on Aging interdisciplinary workshop report reviews myosteatosis—skeletal muscle fat infiltration—as an aging-related ectopic fat depot linked to impaired muscle quality, mobility, metabolism, and mortality. It summarizes evidence across imaging, epidemiology, circadian biology, muscle-bone interactions, and interventions, and calls for standardized definitions, measures, and longitudinal studies.

Key findings

  • Myosteatosis includes intermuscular adipose tissue (IMAT), intramuscular adipose tissue, and intramyocellular lipids (IMCL); it increases with aging and is associated with lower muscle mass, strength, mobility, and disrupted metabolism, including insulin resistance and diabetes.
  • In the Health ABC Study (>3,000 men and women, 70–79 years at baseline), low muscle attenuation was associated with higher muscle fat, older age, and decreased specific force; 5-year CT data showed all individuals gained IMAT, even those who lost weight, while subcutaneous adipose tissue decreased.
  • In the LIFE pilot study, 42 older adults randomized to physical activity or control: controls showed an average 17% increase in IMAT over “one year of aging,” whereas the physical activity group had no apparent increase; physical activity prevented age-associated strength loss but not muscle mass loss.
  • The workshop highlighted unresolved issues in assessment and treatment: no gold-standard imaging method for myosteatosis, DXA bias in lean mass estimates, D3-creatine dilution variability, and potential interventions including physical activity, myostatin treatment, and calorie restriction.

Methods

  • Design: Interdisciplinary workshop convened by the National Institute on Aging Division of Geriatrics and Clinical Gerontology in September 2018; the paper is a narrative report of workshop presentations and discussions.
  • Data or sample: No new primary data were collected; the report synthesizes cited human and animal studies, including cohorts such as Health ABC, LIFE, AGES-Reykjavik, Tobago Bone Health Study, and cancer survivor cohorts.
  • Main analysis: Narrative, cross-disciplinary synthesis of evidence on myosteatosis determinants, clinical consequences, body composition and imaging assessment, metabolism, circadian clocks, muscle-bone interactions, and preventive/therapeutic approaches.

Limitations

  • Stated in the paper: lack of a standard definition and standardized assessment of myosteatosis; non-standardized measures limit cross-study comparison; few longitudinal studies, small sample sizes in some areas, limited racial/ethnic data, no established gold-standard imaging device, and conflicting mortality findings.
  • Stated in the paper: D3-creatine dilution showed large intra-subject variability between repeat measures, and DXA may substantially bias lean mass estimates relative to MRI.
  • Evident from the text: this is a workshop/consensus-style narrative report rather than a systematic review or primary study; no formal search strategy, risk-of-bias assessment, or meta-analysis is described, and many cited findings are preclinical or from selected populations.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3389/fphys.2020.00963

Cites

135 of 135 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 186 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    The higher the IMCL content, the more severe the insulin resistance.

    “The higher the IMCL content, the more severe the insulin resistance.”
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    • cites Goodpaster et al., 2000 source

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    • cites Kelley and Goodpaster, 2001

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  • Premisecitation

    This was the first study demonstrating a correlation between myosteatosis, muscle quality, and weakness in older subjects.

    “This represented the first study demonstrating a correlation between myosteatosis, muscle quality, and weakness in older subjects.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    Various studies in mice and rats demonstrated a strong relationship between muscle DAG content and muscle insulin resistance.

    “various studies in mice and rats having demonstrated a strong relationship between muscle DAG content and muscle insulin resistance (Petersen and Shulman, 2017, 2018).”
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    • cites Petersen and Shulman, 2017 source

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    • cites Petersen and Shulman, 2018 source

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  • Premisecitation

    Myosteatosis disrupts metabolism, including insulin resistance and diabetes.

    “and disrupt metabolism (insulin resistance, diabetes)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Krssak et al., 1999 source

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  • Interpretationreasoning

    Increases in IMAT are a more consistent signature of aging than traditional sarcopenia.

    “This suggests that increases in IMAT are a more consistent signature of aging than traditional sarcopenia.”
    Quote in the paperSubstantial claim
  • May combine two claims. 98
  • Classified as probably not a substantial claim. 26

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    Premisecitation

    In highly trained athletes, an inverse relationship between insulin sensitivity and IMCL content is not observed; despite high insulin sensitivity, they show high IMCL storage (athlete's paradox).

    “In contrast to those who are obese, an inverse relationship between insulin sensitivity and IMCL content is not observed in highly trained athletes. Despite having a high insulin sensitivity, these athletes show a high amount of IMCL storage (“athlete’s paradox”; Goodpaster et al., 2001b).”
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    • cites Goodpaster et al., 2001b

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    Premisenone given

    Obese, sedentary subjects and normal-weight trained subjects had about the same amount of muscle triglyceride, consistent across muscle fiber types.

    “Obese, sedentary subjects and normal-weight trained subjects (men and women, late 60s to early 70s), had about the same amount of muscle triglyceride, and this was consistent across muscle fiber types.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Myosteatosis negatively correlates with muscle mass, strength, and mobility.

    “is recognized to negatively correlate with muscle mass, strength, and mobility”
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    • cites Goodpaster et al., 2000 source

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    • cites Goodpaster et al., 2001a

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    Premisecitation

    In obese and type 2 diabetic patients, muscle DAG content and PKCθ translocation show a strong relationship with muscle insulin resistance, whereas muscle ceramide content shows no correlation.

    “Szendroedi et al. (2014) showed a strong relationship between muscle DAG content, PKCθ translocation and muscle insulin resistance in obese and type 2 diabetic patients, whereas no correlation with muscle ceramide content and muscle insulin resistance was seen in these subjects.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Szendroedi et al., 2014 source

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    Premisecitation

    Low muscle attenuation (low muscle density) is associated with higher fat content in the muscles, age, and decreased specific force.

    “Low muscle attenuation (low muscle density) was associated with higher fat content in the muscles, age, and decreased specific force (the functional outcome of reduced muscle quality; Goodpaster et al., 2000, 2001a).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Goodpaster et al., 2000 source

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    • cites Goodpaster et al., 2001a

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  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    The potential determinants of myosteatosis have not been clearly established, with numerous gaps in understanding the pathophysiologic mechanisms that compromise muscle mass, strength, and quality and disrupt metabolism.

    “The potential determinants of myosteatosis have not been clearly established, with numerous gaps in the understanding of the pathophysiologic mechanisms that compromise muscle mass, strength, and quality and disrupt metabolism.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Myosteatosis is not synonymous with sarcopenia; it appears to be independent of muscle mass and perhaps acts synergistically.

    “Myosteatosis is not synonymous with sarcopenia (loss of muscle mass and function); it does appear to be independent of muscle mass and perhaps act synergistically.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    In the Health ABC Study, traditional sarcopenia was observed in cross-sectional analyses, with a significant decline in muscle size as people age.

    “Traditional sarcopenia was observed in cross-sectional analyses, with a significant decline in muscle size as people age.”
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    • cites Newman et al., 2003

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  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Intermuscular, intramuscular, and intramyocellular fat provide slightly different measures of myosteatosis and may represent different risk factors to metabolic and muscle health, particularly in older adults.

    “Intermuscular, intramuscular, and intramyocellular fat all provide a slightly different measure of myosteatosis and may represent different risk factors to metabolic and muscle health particularly in older adults.”
    Quote in the paperNot a substantial claim

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    Premisenone given

    Obese subjects with and without diabetes who lose weight reduce their IMCL content and improve insulin sensitivity.

    “Obese subjects with and without diabetes who lose weight essentially reduce their IMCL content and improve their insulin sensitivity.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Physical activity prevented the age-associated loss of strength, but this finding could not be explained by prevention of loss of muscle mass.

    “Physical activity prevented the age-associated loss of strength, but this finding could not be explained by the prevention of loss of muscle mass.”
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    • cites Goodpaster et al., 2008

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    Premisecitation

    Amati et al. found ceramides related to insulin resistance, whereas total DAG was not; electron microscopy recapitulated the athlete's paradox.

    “In contrast, Amati et al. (2011) found that ceramides were related to insulin resistance, whereas total DAG assessed in a cross-sectional comparison of percutaneous muscle biopsies in insulin-sensitive vs. insulin-resistant subjects was not; analyses of lipid droplet content by electron microscopy recapitulated the athlete’s paradox.”
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    • cites Amati et al., 2011

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    Premisecitation

    The physical activity group showed no apparent increase in IMAT but a significant attenuation.

    “The physical activity group showed no apparent increase in IMAT but a significant attenuation.”
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    • cites Goodpaster et al., 2008

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    Premisecitation

    In individuals who lost weight, SAT decreased substantially, but all individuals gained IMAT.

    “In individuals who lost weight, SAT was decreased in a substantial way, but in contrast, all individuals gained IMAT.”
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    • cites Delmonico et al., 2009 source

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    Premisecitation

    Ceramide levels were higher in obese and insulin-resistant individuals compared to insulin-sensitive muscle, but DAG content (total and saturated) was higher in insulin-sensitive muscle.

    “Ceramide levels were higher in obese and insulin-resistant individuals compared to insulin-sensitive muscle, but DAG content (total and saturated) was actually higher in insulin-sensitive muscle.”
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    • cites Perreault et al., 2018 source

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    Premisecitation

    IMAT responded uniquely compared to other fat depots as no effect of physical activity was detected in SAT.

    “IMAT responded uniquely compared to other fat depots as no effect of physical activity was detected in the SAT.”
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    • cites Goodpaster et al., 2008

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    Interpretationcitation

    These findings re-emphasize the mechanistic importance of lipid characteristics, as well as the intracellular distribution of lipids in mediating insulin resistance.

    “These findings re-emphasize the mechanistic importance of lipid characteristics, as well as the intracellular distribution of lipids in mediating insulin resistance (Cantley et al., 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cantley et al., 2013

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    Premisecitation

    Fatty infiltration is inversely related to muscle specific force, suggesting that as IMAT increases, even when normalized for muscle cross-sectional area, muscle quality decreases.

    “As previously mentioned, fatty infiltration is inversely related to muscle specific force, suggesting that as IMAT increases, even when normalized for muscle cross-sectional area, muscle quality decreases (Goodpaster et al., 2001a; Hilton et al., 2008).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Goodpaster et al., 2001a

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    • cites Hilton et al., 2008

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    Premisecitation

    Following a tenotomy and neurotomy in the rotator cuff injury in a mouse model, a large and accelerated increase in the accumulation of adipose tissue was observed, with this increase generally related to a negative prognostic factor for recovery from a rotator cuff tear.

    “Following a tenotomy and neurotomy in the rotator cuff injury in a mouse model, a large and accelerated increase in the accumulation of adipose tissue was observed (Kim et al., 2012), with this increase generally related to a negative prognostic factor for recovery from a rotator cuff tear.”
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    • cites Kim et al., 2012

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    Premisecitation

    Using P16-expressing cells, Justice et al. showed a very strong link between the abundance of senescent-like cells and IMAT, and that this was strongly and inversely associated with functional measures like gait speed and SPPB score.

    “Using P16-expressing cells (associated with cellular senescence), Justice et al. (2018) showed a very strong link between the abundance of senescent-like cells and IMAT, and that this was strongly and inversely associated with functional measures like gait speed and Short Physical Performance Battery (SPPB) score.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Justice et al., 2018 source

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    Premisecitation

    Individuals with African ancestry have greater levels of myosteatosis but lower levels of other ectopic fat depots such as fat in the liver or other visceral adipose tissue (VAT).

    “Individuals with African ancestry have greater levels of myosteatosis but lower levels of other ectopic fat depots such as fat in the liver or other visceral adipose tissue (VAT).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The Health ABC study did not find significant racial differences in the rate of myosteatosis with aging likely because of its much older and relatively healthy population.

    “The Health ABC study did not find significant racial differences in the rate of myosteatosis with aging likely because of its much older and relatively healthy population (Delmonico et al., 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Delmonico et al., 2009 source

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    Premisecitation

    Some found no interaction between age and sex, implying that aging was not responsible for the sex difference in myosteatosis rates.

    “Some found no interaction between age and sex, implying that aging was not responsible for the sex difference in myosteatosis rates (Anderson et al., 2013; Xiao et al., 2018).”
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    • cites Anderson et al., 2013

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    Premisecitation

    Those who maintained their thigh muscle area also maintained their gait speed, whereas those with greatest accumulation of thigh IMAT had greater declines in gait speed.

    “Those who maintained their thigh muscle area also maintained their gait speed, whereas those with greatest accumulation of thigh IMAT had greater declines in gait speed.”
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    • cites Beavers et al., 2013

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    Premisenone given

    Sphingolipid and ceramide content in muscle biopsies show a robust association with mitochondrial function, with cardiolipin and some genes/proteins related to atrophy signaling strongly associated with muscles' ceramide content.

    “Sphingolipid and ceramide content in muscle biopsies show a robust association with mitochondrial function, with cardiolipin (a marker of mitochondrial content) and some of the genes and proteins related to atrophy signaling (atrogin-1 and caspase-9) being strongly associated with muscles’ ceramide content.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    In community-dwelling adult fallers and non-fallers, while lean tissue was similar, fallers had increased amounts of myosteatosis across all muscles, with significantly higher amounts in the gluteus maximus and medius/minimus muscles.

    “While lean tissue was similar between both groups, fallers had increased amounts of myosteatosis across all muscles, with significantly higher amounts noted in the gluteus maximus and medius/minimus muscles, suggesting more proximal muscles may be vulnerable to myosteatosis and relevant to balance function in older adults.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Inacio et al., 2014

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    Premisecitation

    Shoulder injury in animals and humans shows that fatty infiltration characterizes the disease course and its degree is associated with poorer recovery.

    “Shoulder injury in animals and humans shows that fatty infiltration characterizes the disease course and its degree is associated with poorer recovery.”
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    • cites Kim et al., 2012

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    Premisecitation

    Gallagher et al. showed that IMAT was greater in African-Americans but only at greater levels of total body fat.

    “Gallagher et al. (2005) showed that IMAT was greater in African-Americans but only at greater levels of total body fat.”
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    • cites Gallagher et al., 2005

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    Premisecitation

    Myosteatosis is related to increased frailty and decreased muscle and mobility function in both the upper and lower extremities.

    “Myosteatosis is related to increased frailty and decreased muscle and mobility function in both the upper and lower extremities.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Song et al. followed a small sample of 26 African-American older women over 2 years and showed significant increases in IMAT.

    “Song et al. (2004) followed a small sample of 26 African-American older women over 2 years and showed significant increases in IMAT.”
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    • cites Song et al., 2004 source

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    Premisecitation

    Increases in myosteatosis in the abdominal, psoas and hip muscles relate to increased gait variability, kyphosis progression, decreased balance, and an increased risk of falls.

    “These studies generally report that increases in myosteatosis in the abdominal, psoas and hip muscles, relate to increased gait variability (Addison et al., 2014a,b), kyphosis progression (Lorbergs et al., 2019), decreased balance (Addison et al., 2014a,b), and an increased risk of falls (Visser et al., 2002; Addison et al., 2014a,b, 2017; Inacio et al., 2014).”
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    • cites Addison et al., 2014a,b

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    • cites Lorbergs et al., 2019

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    Premisecitation

    Although increased age affects accumulation of fat in all abdominal muscles, such effect might be larger in the paraspinal compared to the psoas muscle.

    “Although increased age affects accumulation of fat in all abdominal muscles, such effect might be larger in the paraspinal compared to the psoas muscle (Anderson et al., 2013).”
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    • cites Anderson et al., 2013

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    Premisecitation

    These individuals showed higher amounts of myosteatosis in their hip abductors and a lower hip abductor torque production, suggesting fatty infiltration of the hip abductors may be important to evaluate when looking at balance and mobility changes in older adults.

    “These individuals showed higher amounts of myosteatosis in their hip abductors and a lower hip abductor torque production, suggesting fatty infiltration of the hip abductors may be important to evaluate when looking at balance and mobility changes in older adults.”
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    • cites Addison et al., 2017

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    Premisecitation

    MRI assessment of the calf identified higher amounts of lipid in the gastrocnemius muscle; lipid in the tibialis and soleus were similar in normal-weight and obese subjects.

    “Magnetic resonance imaging (MRI) assessment of the calf identified higher amounts of lipid in the gastrocnemius muscle; lipid in the tibialis and soleus were similar in normal-weight and obese subjects (Perreault et al., 2018).”
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    • cites Perreault et al., 2018 source

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    Premisecitation

    Some ceramides and sphingolipids in the cytosol are related to insulin resistance and some DAGs relate to better insulin sensitivity; some ceramides or DAGs in the nucleus are linked to either insulin resistance or better insulin sensitivity.

    “Some of the ceramides and sphingolipids in the cytosol are related to insulin resistance and some of the DAGs relate to better insulin sensitivity; some of the ceramides or DAGs in the nucleus are linked to either insulin resistance or better insulin sensitivity (Perreault et al., 2018).”
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    Premisenone given

    In general, Hispanic adolescents have more myosteatosis compared to whites independent of total adiposity.

    “In general, Hispanic adolescents have more myosteatosis compared to whites independent of total adiposity.”
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    Premisenone given

    In men, muscle attenuation or IMAT shows a clear positive association with mortality; in women, only muscle attenuation (not IMAT) is associated with mortality.

    “When muscle attenuation or IMAT was examined, men showed a clear positive association with mortality, while in women only muscle attenuation (not IMAT) was associated with mortality.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Increased fatty infiltration of cardiac muscles is observed in diabetes and correlates with diastolic dysfunction.

    “Myosteatosis implication in the prognosis and survival post liver transplantation (Hamaguchi et al., 2014), increased fatty infiltration of cardiac muscles observed in diabetes and correlation with diastolic dysfunction have been documented (McGavock et al., 2007).”
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    • cites McGavock et al., 2007

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    Premisenone given

    Myosteatosis quantification can be performed invasively using muscle biopsy and noninvasively using CT, pQCT, and MRI.

    “Myosteatosis quantification can be performed using invasive analysis such as a muscle biopsy, but it can also be conducted noninvasively using imaging devices such as CT, peripheral quantitative computed tomography (pQCT), and MRI.”
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  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The conflicting findings on myosteatosis and mortality may relate to the definitions and measures used to assess myosteatosis, as well as the muscle(s) examined.

    “These conflicting findings may relate to the definitions and measures used to assess myosteatosis, as well as the muscle(s) examined.”
    Quote in the paperSubstantial claim

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    Premisecitation

    In a group of 100 participants with pancreatic and periampullary adenocarcinomas, 40% were sarcopenic, 25% had myosteatosis, and 11% had both.

    “In a group of 100 participants with pancreatic and periampullary adenocarcinomas, 40% were sarcopenic, 25% had myosteatosis, and 11% had both (Stretch et al., 2018).”
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    • cites Stretch et al., 2018 source

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  • May combine two claims.

    Premisenone given

    Inter and intramuscular adipose tissue are identifiable with CT and MRI; IMCL requires more specialized imaging techniques such as MRS or muscle biopsies.

    “While inter and intramuscular adipose tissue are identifiable with CT and MRI, IMCL requires more specialized imaging techniques to visualization and quantification such as magnetic resonance spectroscopy (MRS) or muscle biopsies.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    There is no established gold standard device to quantify myosteatosis.

    “However, there is no established gold standard device to quantify myosteatosis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Myosteatosis has been reported as an independent risk factor for hip fracture, diabetes, disability, hospitalization, mortality, severe illness outcome, and surgery in the very ill.

    “Myosteatosis has been reported as an independent risk factor for hip fracture, diabetes, disability, hospitalization, mortality, severe illness outcome, and surgery in the very ill.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premiseown data

    Low muscle mass and poorer strength are independent risk factors.

    “Low muscle mass and poorer strength continued to be independent risk factors.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Recommended cutpoint for grip strength is 26 kg for men and 16 kg for women.

    “Efforts to create cutpoints for muscle mass and muscle strength from population studies (community-dwelling older adults) recommended cutpoint for grip strength of 26 kg for men vs. 16 kg for women, and for appendicular lean body mass (measured with DXA) of 19.75 kg for men vs. 15.02 kg for women (Alley et al., 2014; Cawthon et al., 2014).”
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    • cites Alley et al., 2014 source

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    • cites Cawthon et al., 2014

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    Premisecitation

    The biological mechanisms of increased myosteatosis are currently unknown, though multiple theories have been presented including defective leptin signaling, involvement of skeletal muscle precursor stem cells or fibroadipogenic precursor (FAP) cells, neuromuscular changes resulting in decreased regenerative capacity, and mitochondrial dysfunction.

    “The biological mechanisms of increased myosteatosis are currently unknown, though multiple theories have been presented including defective leptin signaling (Koteish and Diehl, 2001), the involvement of skeletal muscle precursor stem cells (Kirkland et al., 2002) or fibroadipogenic precursor (FAP) cells (Farup et al., 2015), neuromuscular changes resulting in decreased regenerative capacity (Tak”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Koteish and Diehl, 2001

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    • cites Farup et al., 2015

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  • May combine two claims.

    Interpretationnone given

    Myosteatosis has been implicated in numerous negative aging-related outcomes, with resultants such as mobility-disability, metabolic impairments, and increased mortality making myosteatosis a priority research area to help clinicians identify and manage at risk older adults.

    “Myosteatosis has been implicated in numerous negative aging-related outcomes, with resultants such as mobility-disability, metabolic impairments, and increased mortality making myosteatosis a priority research area to help clinicians identify and manage at risk older adults.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Low muscle density is associated with poor survival and increased risk of hospitalization.

    “Low muscle density has also been associated with poor survival and increased risk of hospitalization (Cawthon et al., 2009; Looijaard et al., 2016).”
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    • cites Cawthon et al., 2009 source

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    • cites Looijaard et al., 2016 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    QUS is emerging as a feasible, inexpensive, and easy device to use for myosteatosis quantification.

    “Quantitative ultrasound (QUS) is emerging as a feasible, inexpensive, and easy device to use for the same purpose.”
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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    CT is one of the most widely used imaging tools to indirectly assess myosteatosis, especially in large cohorts.

    “CT is one of the most widely used imaging tools to indirectly assess myosteatosis, especially in large cohorts.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premiseown data

    In the Kaiser Permanente colorectal cancer cohort, a 30% increase in mortality for those with low muscle and a 20% increase in mortality for those with high adiposity were observed.

    “In the cohort of colorectal cancer, a 30% increase in mortality for those with low muscle and a 20% increase in mortality for those with high adiposity were observed.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Inter-machine validity and optimal methods/criteria to characterize muscle tissue for ultrasound are currently unknown.

    “The inter-machine validity as well as the optimal methods and criteria to characterize muscle tissue are currently unknown.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    MRI can be expensive and time intensive.

    “MRI can also be expensive and time intensive.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    pQCT cannot isolate individual muscle groups and cannot clearly distinguish intra vs. IMAT.

    “Individual muscle groups cannot be isolated with pQCT, and intra vs. IMAT cannot be clearly distinguished.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given

    Creatine is a key component of muscle energetics, acts on regeneration of ATP from ADP, and is 95% exclusively located in muscles.

    “Creatine is a key component of muscle energetics and acts on the regeneration of adenosine triphosphate (ATP) from adenosine biphosphate (ADP) and has a unique feature of being 95% exclusively located in muscles.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    IMCL measurement can be done with MRI/MRS, but device is unlikely available at most facilities and cannot be applied to all muscles or individuals with metal implants.

    “While the measurement of IMCL can be done with MRI (utilizing MRS), the device is unlikely to be available at most facilities and cannot be applied to all muscles or in individuals with metal implants such as joint replacements.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Obesity is associated with increased risk for cardiovascular disease.

    “While obesity is associated with an increased risk for cardiovascular disease, there is a need for further stratification of patients’ risks that existing body phenotypes cannot provide (Vecchie et al., 2018).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Vecchie et al., 2018

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    MRI can quantitate amount of fat within muscle, but quantitative assessment of muscle density with MRI is not available.

    “The amount of fat within a muscle can be quantitated (i.e., cross-sectional area of volume), however, at this time a quantitative assessment of muscle density with MRI is not available.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    pQCT devices are portable.

    “pQCT devices are portable, making them useful for research populations in difficult-to-reach locations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In single-dose human studies, DXA vs MRI comparison showed a great deal of bias; DXA resulted in almost a doubling of total lean mass estimated by DXA.

    “In single-dose human studies where muscle mass was evaluated in all subjects by MRI (serial cross-sections) and total lean body mass as well as appendicular lean mass were evaluated by DXA, comparison of DXA vs. MRI showed a great deal of bias in that measurements resulted in almost a doubling of the total lean mass estimated by DXA.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Clark et al., 2014

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    DXA is commonly available for clinical use due to lower radiation levels and ease of use.

    “DXA is a commonly available option for clinical use due to its lower radiation levels and ease of use.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    DXA-derived subcutaneous fat thickness was a strong marker for hip fracture; thigh muscle attenuation evaluated by DXA had no predictive value for fracture risk.

    “Although DXA derived subcutaneous fat thickness was a strong marker for hip fracture, thigh muscle attenuation evaluated by DXA had no predictive value for fracture risk.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Malkov et al., 2015

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    MRI provides high-quality images allowing distinction of muscle groups and fat depots with excellent reproducibility and reliability.

    “MRI provides a high-quality image allowing for muscle groups and fat depots (intra vs. IMAT) to be distinguished and visualized with excellent reproducibility and reliability.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    CT has excellent reproducibility and reliability that allows 3D reconstruction and selection of axial or appendicular anatomical sites.

    “CT has excellent reproducibility and reliability that allows 3D reconstruction and selection of axial or appendicular anatomical sites, though the use of a phantom may be necessary to standardize attenuation values across studies.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The lower leg is most often used with highest reproducibility in the area where the muscle belly is the largest.

    “While the thigh can be measured in scanners with a larger gantry, the lower leg (generally two-thirds of the length of the lower leg serve as a site for analysis) is most often used with a highest reproducibility in the area where the muscle belly is the largest.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    There are issues with psychomotor components of scanning such as consistency of probe placement, pressure, and angle of incidence.

    “There are also issues with the psychomotor components of scanning such as consistency of probe placement, pressure, and the angle of incidence.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    With aging, magnitude of echogenicity measures is higher in older adults, but pattern between muscles does not differ between younger and older individuals.

    “With aging the magnitude of echogenicity measures are higher in older adults, but the pattern between muscles does not differ between younger and older individuals.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    There are likely differences in body shape between those with high and low muscle density; someone with poor-quality muscle and high myosteatosis is unlikely to physically resemble someone with high-quality muscle.

    “It is likely that there are differences in the way that the body is shaped in those with high and low muscle density and unlikely that someone with poor-quality muscle and high levels of myosteatosis physically resembles someone with high-quality muscle.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Major methods to evaluate muscle mass include MRI, DXA, and 24-h urine collection.

    “Major methods utilized to evaluate muscle mass include MRI, DXA, and a 24-h urine collection.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Echogenicity may be used to examine tissue composition and is associated with general muscle performance and metabolic parameters.

    “Echogenicity (ultrasound’s brightness) may be used to examine tissue composition (Akima et al., 2016) and is associated with general muscle performance, as well as metabolic parameters (Harris-Love et al., 2018).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Akima et al., 2016

      Not checked in the free run.

    • cites Harris-Love et al., 2018

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    MRI can quantify myosteatosis and has no ionizing radiation.

    “MRI can be used to quantify myosteatosis with one clear advantage over CT devices: no ionizing radiation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    There is no standard analysis protocol for pQCT, and manual segmentation of muscles may be necessary.

    “While pQCT permits the assessment of muscle density, there is no standard analysis protocol, and manual segmentation of muscles may be necessary, creating problems with reproducibility and comparison across studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    pQCT devices have lower cost and significantly lower emission of ionizing radiation compared to whole-body CT.

    “When used to measure muscles, pQCT devices have the benefit of a lower cost and significantly lower emission of ionizing radiation compared to whole-body CT (Erlandson et al., 2016).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Erlandson et al., 2016

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Skeletal muscles and liver are major organs involved in insulin resistance; skeletal muscle is a major site of insulin-stimulated glucose disposal.

    “The skeletal muscles and the liver are the major organs involved in the cellular and molecular basis of the insulin resistance process, and the skeletal muscle is a major site of insulin stimulated glucose disposal.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    The ratio of rectus to deltoid echogenicity is maintained in 20-year-olds and 65-year-olds, but absolute echogenicity values increase in older adults.

    “When comparing the rectus to the deltoid muscle, the ratio of how bright the rectus muscle is compared to the deltoid is maintained in the 20-year-olds as well as in the 65-year-olds, but the echogenicity absolute values (i.e., change in muscle composition) increase in older adults.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    For appendicular lean mass, DXA had good correlation (r=0.957) but underestimated lean mass compared to MRI.

    “When looking at just appendicular lean mass estimates with DXA, there was a good correlation (r = 0.957), but DXA underestimated lean mass resulting in a significant lower amount of appendicular lean mass than the actual value was per MRI.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Clark et al., 2014

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Detailed models of body shape and tissue distribution with DXAs accurately identify sex and race and predict mortality.

    “Importantly, these detailed models of body shape and tissue distribution with DXAs were able to accurately identify sex and race, as well as predict mortality.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Shepherd et al., 2017

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The decrease in specific force indicates changes in muscle quality, as there were no changes in muscle size.

    “The decrease in specific force is a clear indication that there are changes in muscle quality as there were no changes in muscle size.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    These data demonstrate importance of genetic predispositions to reductions in mitochondrial activity, development of ectopic lipid, insulin resistance, and diabetes.

    “These data demonstrate the importance of genetic predispositions to reductions in mitochondrial activity, development of ectopic lipid, insulin resistance, and diabetes.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Circadian clocks exist in virtually all cells including skeletal muscle and regulate certain metabolic and cell physiologic processes.

    “Circadian clocks exist in virtually all cells in the body including skeletal muscles and is a ubiquitous mechanism that functions to temporarily regulate certain metabolic and cell physiologic processes (Harfmann et al., 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Harfmann et al., 2015 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Circadian rhythm changes with aging.

    “There is growing recognition that circadian rhythm changes with aging (Hood and Amir, 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Hood and Amir, 2017

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Loss of Bmal1 only in skeletal muscle is enough to induce significant weakness with diminished forelimb grip strength and loss of specific force in mice.

    “What both studies found was that loss of Bmal1 only in skeletal muscle was enough to induce significant weakness with diminished forelimb grip strength and a loss of specific force (determined as the maximum isometric force normalized to muscle cross sectional area).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Dyar et al., 2014

      Not checked in the free run.

    • cites Schroder et al., 2015

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In mice with NAT-1 knockout, there is reduced whole body energy expenditure and reduced oxygen consumption in white adipose tissue, brown adipose tissue, and liver.

    “In mice with a NAT-1 knockout, there is reduced whole body energy expenditure (Camporez et al., 2017) and reduced oxygen consumption in white adipose tissue, brown adipose tissue, and the liver.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Camporez et al., 2017

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Aged wild type mice develop muscle insulin resistance associated with increased muscle lipid (TAG/DAG) content (but no change in ceramide) and reduced muscle mitochondrial function.

    “Like humans, it was found that aged wild type mice develop muscle insulin resistance, which was associated with increased muscle lipid (TAG/DAG) content (but no change in muscle ceramide content) and reduced muscle mitochondrial function.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lee et al., 2010 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both VAT and IMAT cause insulin resistance in vitro, with IMAT showing similar potency to VAT.

    “Using condition media generated from SAT, VAT, and IMAT, it was shown that both VAT and IMAT cause insulin resistance in vitro, with IMAT showing a similar potency to VAT (Sachs et al., 2019).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Sachs et al., 2019 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In response to 2-h glucose tolerance test, 70-year-olds showed slightly higher plasma glucose but much larger increases in plasma insulin reflecting whole body insulin resistance.

    “In response to the 2-h glucose tolerance test, the 70-year-olds showed slightly higher plasma concentrations of glucose, but much larger increases in the plasma concentration of insulin reflecting whole body insulin resistance.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Petersen et al., 2003 source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Infusion of lipid in healthy rats or mice results in profound insulin resistance within 4-5 h, with plasma fatty acids going up.

    “Infusion of lipid in healthy rats or mice results in profound insulin resistance within 4–5 h, with plasma fatty acids going up.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A fatty acid derived metabolite (e.g., DAG) has been suggested to mediate reduced insulin signaling and insulin action.

    “IMCL is a strong predictor of insulin resistance in sedentary individuals (Krssak et al., 1999) and muscle insulin resistance can be induced within 5-hours of a lipid infusion in healthy individuals (Dresner et al., 1999), and a fatty acid derived-metabolite (e.g., DAG) has been suggested to be responsible for mediating reduced insulin signaling and insulin action.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Pre-clinical data suggest that mitochondrial function decreases with aging, in part due to cumulative ROS damage, and predisposes individuals to ectopic lipid (DAG) build-up in muscle and muscle insulin resistance.

    “Taken together, these pre-clinical data suggest that mitochondria function decreases with aging, in part due to cumulative ROS damage, and predisposes individuals to ectopic lipid (DAG) build-up in muscle and muscle insulin resistance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    RNAseq analysis showed higher levels of macrophage infiltration in obesity and type 2 diabetes that correlated with insulin resistance in all individuals.

    “RNAseq analysis showed higher levels of macrophage infiltration in those with obesity and type 2 diabetes that correlated with insulin resistance in all individuals.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Sachs et al., 2019 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the study, VAT and IMAT were taken from two separate populations: SAT and VAT from bariatric surgery patients with average BMI 45, IMAT from mid-BMI range (around 33) and likely more metabolically healthy.

    “Importantly, the VAT and IMAT in this study were taken from two separate populations. SAT and VAT were taken from patients undergoing bariatric surgery with an average BMI of 45 kg/m2. The IMAT came from individuals who were mid-BMI range (around 33 kg/m2) and most likely more metabolically healthy.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Sachs et al., 2019 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Healthy older adults had twice the amount of IMCL compared to younger individuals, associated with a 35-40% reduction of muscle mitochondrial fat oxidation and ATP synthesis.

    “The healthy older adults also had twice the amount of IMCL compared to the younger individuals as assessed by 1H MRS, which was associated with a 35–40% reduction of muscle mitochondrial fat oxidation as assessed by 13C MRS and muscle mitochondrial ATP synthesis as assessed by 31P MRS (Petersen et al., 2003).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Petersen et al., 2003 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NAT-1 knockout mice display increased ectopic lipid in liver and muscle, and muscle and liver insulin resistance.

    “The NAT-1 knockout mice also display increased ectopic lipid in the liver and muscle, as well as muscle and liver insulin resistance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    More sedentary individuals are more likely to have their muscle clocks affected, which in combination with reduced physical activity may lead to myosteatosis.

    “Thus, the more sedentary individuals become the more likely they are to have their muscle clocks affected, which, in combination with the reduced physical activity, may lead to myosteatosis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In OPTIMA, intramuscular fat in the thigh decreased in proportion to overall fat loss, but no significant change in muscle attenuation was seen.

    “Intramuscular fat in the thigh decreased in proportion to overall fat loss, but no significant change in muscle attenuation was seen.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Shea et al., 2011 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Pericardial fat is related to increased coronary calcification and stiffness in large arteries.

    “Pericardial fat is related to increased coronary calcification and stiffness in large arteries (McClain et al., 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites McClain et al., 2013

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Increased myosteatosis likely decreases ability to activate a muscle, making it more difficult to stop fat accumulation once started.

    “However, one potential consequence of increased myosteatosis is likely a decreased ability to activate a muscle, making it more difficult to stop the accumulation of fat once it has started.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    Increased marrow adiposity may have potential benefits for some outcomes, suggesting unexamined positive benefits of myosteatosis.

    “That increased marrow adiposity may have potential benefits for some outcomes but also suggests there may be some unexamined positive benefits of myosteatosis that require further study.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In the C3H mouse, early progression of bone marrow adipose tissue occurs, and the mouse has increased marrow fat but a denser skeleton with higher bone mass.

    “In the C3H mouse, early progression of bone marrow adipose tissue occurs (Scheller et al., 2015). While this may initially appear negative, the C3H mouse has not only a tremendous increase in marrow fat, but a much denser skeleton with higher bone mass.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Scheller et al., 2015

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the OPTIMA study, average 6.5% total weight loss was achieved, with approximately 14% and 9.7% total body fat loss in men and women, respectively.

    “Over the course of the intervention an average of 6.5% total weight loss was achieved, with approximately 14 and 9.7% total body fat loss in men and women, respectively.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Shea et al., 2011 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In mice, short-term treatment with an antimyostatin antibody increases whole body muscle mass, grip strength, and insulin action.

    “In mice, even short-term treatment (approximately 4-weeks) with an antimyostatin antibody results in increased whole body muscle mass, grip strength, and insulin action (Camporez et al., 2016).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Camporez et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Muscles from Bmal1 knockout mice exhibit reduced glycolytic enzyme activity and reduced GLUT-4 expression, suggesting the molecular clock regulates muscle mechanisms impacting glucose uptake.

    “Muscles from Bmal1 knockout mice exhibit reduced glycolytic enzyme activity (e.g., 50% reduction in both hexokinase and phosphofructokinase activity) and a significant reduction in expression of the glucose transporter type 4 (GLUT-4) suggests that the molecular clock regulates muscle mechanisms that impact glucose uptake in muscle (Harfmann et al., 2016).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Harfmann et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In that program, normal-density muscles were relatively preserved, but the low-density component (indicating increased myosteatosis) was lost.

    “While they experienced a loss of muscle mass, their muscle composition also changed, with their normal-density muscles relatively preserved, but the low-density component (indicting increased myosteatosis) lost during the program.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Shea et al., 2011 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Adiposity in bone marrow occurs with aging and up to 70% of marrow in older adults may be adipocytes.

    “Similar to muscle, adiposity in the bone marrow occurs with aging and up to 70% of marrow in older adults may be adipocytes (Fazeli et al., 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Fazeli et al., 2013

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    For the 4-meter walk, both VAT and IMAT loss are linked to improved walk speed, but this relationship did not significantly affect pericardial fat.

    “For the 4-meter walk, both VAT and IMAT loss are linked to improved walk speed, but this relationship did not significantly affect pericardial fat (Brinkley et al., 2011).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Brinkley et al., 2011

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Among older adults in intensive eccentric resistance training, only those with low myosteatosis at start made changes in muscle quality, suggesting older adults with high myosteatosis may be impaired in making such changes.

    “Among older adults participating in an intensive eccentric resistance training program, only those who had low levels of myosteatosis at the start of the intervention made changes in their muscle quality. This suggests that older adults with high levels of myosteatosis may be impaired with making such changes (Marcus et al., 2013).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Marcus et al., 2013

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In OPTIMA, pioglitazone doubled VAT loss in men, but no statistically significant difference in VAT loss was detected in women.

    “When comparing pioglitazone/no-pioglitazone in men, the use of pioglitazone doubled the amount of VAT loss in men, but in women, no statistically significant difference in VAT loss was detected.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Shea et al., 2011 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Fat in the renal sinus area is associated with harder-to-control blood pressure.

    “Fat in the area of the renal sinus is associated with harder-to-control blood pressure (Chughtai et al., 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Chughtai et al., 2010

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a sheep model of rotator cuff injury, atrophy changes pennation angle, creating space within the fiber that is filled with fat.

    “In a sheep model of rotator cuff injury, the pennation angle of the muscle fibers changes when there is atrophy. This creates a space within the fiber, and this space is filled with fat (Meyer et al., 2004).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Meyer et al., 2004

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Five to six months of moderate calorie restriction leads to about 7-8% loss of total mass, with associated changes in VAT, thigh IMAT, and pericardial fat.

    “Five to six months of moderate calorie restriction leads to about a 7–8% loss of total mass, with associated changes in VAT, thigh IMAT, and pericardial fat (Brinkley et al., 2011).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Brinkley et al., 2011

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In muscle-specific Bmal1 knockout mice, AICAR activation of AMPK does not increase glucose uptake, indicating loss of Bmal1 affects both exercise- and insulin-induced glucose uptake.

    “Further, use of 5-aminoimidazole-4-carboxamide-1-D-ribofuranoside (AICAR) to activate adenosine monophosphate (AMP)-activated protein kinase (AMPK) also did not increase glucose uptake indicating that loss of Bmal1 affects both exercise as well as insulin-induced glucose uptake.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Harfmann et al., 2016 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    High degrees of myosteatosis in large locomotor muscles of lower extremities may have a different role or influence on whole body metabolism compared to smaller muscles in forearm.

    “High degrees of myosteatosis in the large locomotor muscles of the lower extremities may have a different role or influence on whole body metabolism compared to smaller muscles in the forearm.”
    Quote in the paperNot a substantial claim
113 of 113

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A combined assessment of muscle quantity and muscle fat provides a more complete description of muscle health that has been shown to improve performance in identifying high-risk individuals.

    “Therefore, a combined assessment provides a more complete description of muscle health that has been shown to improve the performance in identifying high-risk individuals. [58][59]59][60][61]65,67,69”

    From Changes in lean body mass with <scp>glucagon‐like peptide</scp> ‐1‐based therapies and mitigation strategies (2024) · cites this paper as [65]

    In “Cutpoints for Assessing Lean Mass, Strength, and Predicting Poor Outcomes” (page unavailable), the paper reports that muscle mass and measures of muscle fat relate to adverse outcomes, and argues that including myosteatosis would enhance assessment. It does not report that a combined assessment has been shown to improve performance in identifying high-risk individuals. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Reported associations indicate a stronger link of muscle fat with adverse outcomes as compared with muscle quantity.

    “reported associations indicate a stronger link of muscle fat with adverse outcomes as compared with muscle quantity.60,61,[65][66][67]”

    From Changes in lean body mass with <scp>glucagon‐like peptide</scp> ‐1‐based therapies and mitigation strategies (2024) · cites this paper as [65]

    The Calorie Restriction section says adiposity measures are more strongly related to mobility than muscle mass measures in community-dwelling older adults, and it links intramuscular fat to several adverse outcomes. It does not establish that muscle fat has a stronger association than muscle quantity across adverse outcomes generally; the Cutpoints section reports consistent associations of muscle area with mortality and mobility-disability, while some myosteatosis associations varied by sex and outcome. No page numbers are available in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Muscle strength and muscle fat infiltration are inversely correlated.

    “Muscle strength and muscle fat infiltration are inversely correlated [54]”

    From Obesity pharmacotherapy in older adults: a narrative review of evidence (2025) · cites this paper as [54]

  • Individuals with obesity may have comparable or even higher absolute skeletal muscle mass relative to nonobese counterparts, due to higher overall body mass and potentially higher related muscle workload in daily physical activity.

    “Individuals with obesity may conversely have comparable or even higher absolute skeletal muscle mass relative to nonobese counterparts, due to higher overall body mass and potentially higher related muscle workload in daily physical activity [80, 81].”

    From Definition and Diagnostic Criteria for Sarcopenic Obesity: ESPEN and EASO Consensus Statement (2022) · cites this paper as [81]

  • Ageing increases infiltration of skeletal muscle by adipose tissue (myosteatosis) in multiple depots, including intermuscular adipose tissue and intramyocellular lipids.

    “With ageing, there is an increase in infiltration of skeletal muscle by adipose tissue (termed myosteatosis) within multiple different adipose depots, including intermuscular adipose tissue and intramyocellular lipids55.”

    From Sarcopenic obesity in older adults: a clinical overview (2024) · cites this paper as [55]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Mobility-disability association described as men-only despite a finding in women

    Minor

    The text says the association between myosteatosis and mobility-disability was observed only in men, then says muscle attenuation-a measure of myosteatosis-was linked to increased mobility-disability risk in women.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Kelley, 2001, Skeletal muscle triglyceride. An aspect of regional adiposity and insulin resistance, Diabetes Care, 24, 933, 10.2337/diacare.24.5.933 · DOI

Cited by

Sorted by citations

Authors
Correa-de-Araujo, R., Addison, O., Miljkovic, I., Goodpaster, B. H., Bergman, B. C., Clark, R. V., Elena, J. W., Esser, K. A., Ferrucci, L., Harris-Love, M. O., Kritchevsky, S. B., Lorbergs, A., Shepherd, J. A., Shulman, G. I., & Rosen, C. J.
Affiliations
  • University of Maryland, Baltimore (US)
  • University of Pittsburgh (US)
  • AdventHealth Orlando (US)
  • University of Colorado Anschutz (US)
  • United States Anti-Doping Agency (US)
  • National Institutes of Health (US)
  • University of Florida (US)
  • Wake Forest University (US)
  • Canadian Frailty Network (CA)
  • University of Hawaii Cancer Center (US)
  • Yale University (US)
  • Maine Medical Center Research Institute (US)
Corresponding author
Addison, Odessa
ORCID
Venue
Frontiers in Physiology
Publisher
Frontiers Media SA
Published
2020-08-07
Volume
11
Pages
963-963
ISSN
1664-042X (ISSN-L)
DOI
10.3389/fphys.2020.00963
PMC
PMC7438777
OpenAlex
W3048054064
Semantic Scholar
57ba572b88f0c6fc7dc8502c27e50249604aa05c
Cited by
468
References
135
Citations by year
2026: 79 · 2025: 104 · 2024: 87 · 2023: 76 · 2022: 71 · 2021: 49 · 2020: 1
FWCI
6.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Physiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Veterans Affairs (IK2RX001854)
  • Yale University
  • University of Pittsburgh
  • Maine Medical Center Research Institute
  • Canadian Frailty Network
  • National Institute on Aging (P30AG028740)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK119968, R01DK116774, P30DK048520)
Topics
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
myosteatosis, skeletal muscle fat infiltration, muscle aging, sarcopenia, body composition assessment, dual-energy X-ray absorptiometry, circadian rhythm, muscle-bone interaction, bone marrow adiposity, myostatin, caloric restriction, physical activity, cancer survivors, insulin resistance

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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