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Cited by 1,102Nutrition and Health in AgingMuscle Physiology and DisordersMuscle metabolism and nutrition

Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases

Open access
Kalyani, Rita Rastogi, Corriere, Mark, Ferrucci, Luigi·2014·The Lancet Diabetes & Endocrinology
DOI 10.1016/s2213-8587(14)70034-8PMC PMC4156923
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Abstract

The term sarcopenia refers to the loss of muscle mass that occurs with ageing. On the basis of study results showing that muscle mass is only moderately related to functional outcomes, international working groups have proposed that loss of muscle strength or physical function should also be included in the definition. Irrespective of how sarcopenia is defined, both low muscle mass and poor muscle strength are clearly highly prevalent and important risk factors for disability and potentially mortality in individuals as they age. Many chronic diseases, in addition to ageing, could also accelerate decrease of muscle mass and strength, and this effect could be a main underlying mechanism by which chronic diseases cause physical disability. In this Review, we address both age-related and disease-related muscle loss, with a focus on diabetes and obesity but including other disease states, and potential common mechanisms and treatments. Development of treatments for age-related and disease-related muscle loss might improve active life expectancy in older people, and lead to substantial health-care savings and improved quality of life.

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Crossref · 10.1016/s2213-8587(14)70034-8

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  • Premisecitation

    Age-related muscle loss is a strong risk factor for disability, hospitalisation, and death in older adults.

    “Age-related muscle loss is a strong risk factor for disability, hospitalisation, and death in older adults.10,13”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [10] Fielding, 2011, Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia, J Am Med Dir Assoc source

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    • cites [13] Visser, 2005, Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons, J Gerontol A Biol Sci Med Sci source

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  • Premisecitation

    The decline in muscle strength during ageing is greater than expected from the loss of muscle mass, especially after age 60-70 years.

    “However, it has become clear that decreases in muscle strength exceed what is expected on the basis of the decline in muscle mass during ageing,18 especially after the age of 60–70 years.19”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [18] Goodpaster, 2006, The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study, J Gerontol A Biol Sci Med Sci source

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    • cites [19] Baum, 2009, Comparison of skeletal muscle strength between cardiac patients and age-matched healthy controls, Int J Med Sci source

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  • Premisecitation

    Sarcopenia may affect up to half of people aged 80 years and older.

    “Sarcopenia might affect up to half of people aged 80 years and older, but, without a standard definition, no real estimates of prevalence and incidence are possible.11,12”
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    • cites [11] von Haehling, 2010, An overview of sarcopenia: facts and numbers on prevalence and clinical impact, J Cachexia Sarcopenia Muscle source

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    • cites [12] Volpato, 2013, Prevalence and clinical correlates of sarcopenia in community-dwelling older people: application of the EWGSOP definition and diagnostic algorithm, J Gerontol A Biol Sci Med Sci

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  • Premisecitation

    The cross-sectional area of the vastus lateralis muscle decreases by up to 40% between ages 20 and 80 years.

    “the cross-sectional area of the vastus lateralis (quadriceps) muscle decreases by up to 40% between the ages of 20 and 80 years.16”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Lexell, 1995, Human aging, muscle mass, and fiber type composition, J Gerontol A Biol Sci Med Sci

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  • Interpretationcitation

    Increased expression of E3 enzymes in insulin-resistant individuals contributes to muscle protein degradation by a mechanism not shared by age-related sarcopenia.

    “Increased expression of these E3 enzymes in insulin resistant individuals contributes to muscle protein degradation, a mechanism not shared by age-related sarcopenia.47”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47] Wang, 2006, Insulin resistance accelerates muscle protein degradation: Activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling, Endocrinology source

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  • Classified as probably not a substantial claim. 8

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    Premisecitation

    Low muscle mass and poor muscle strength are common and are important risk factors for disability and possibly death as people age.

    “Irrespective of how sarcopenia is defined, both low muscle mass and poor muscle strength are clearly highly prevalent and important risk factors for disability and potentially mortality in individuals as they age.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [10] Fielding, 2011, Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia, J Am Med Dir Assoc source

      Not checked in the free run.

    • cites [13] Visser, 2005, Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons, J Gerontol A Biol Sci Med Sci source

      Not checked in the free run.

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

    Interpretationnone given

    Developing treatments for age-related and disease-related muscle loss might improve active life expectancy, produce health-care savings, and improve quality of life.

    “Development of treatments for age-related and disease-related muscle loss might improve active life expectancy in older people, and lead to substantial health-care savings and improved quality of life.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    How much chronic diseases such as diabetes and obesity contribute to age-related muscle loss is unclear.

    “The contribution of chronic diseases such as diabetes and obesity, the prevalence of which also increase with ageing, to age-related muscle loss is unclear;”
    Quote in the paperSubstantial claim

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    Premisecitation

    Ageing brings a progressive decline in muscle mass, strength, and quality, along with an increase in fat mass.

    “Ageing is accompanied by major changes in body composition that can negatively affect functional status in older adults, including a progressive decrease in muscle mass, strength, and quality, accompanied by an increase in fat mass.1,2”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [1] Candow, 2005, Differences in size, strength, and power of upper and lower body muscle groups in young and older men, J Gerontol A Biol Sci Med Sci source

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    • cites [2] Lauretani, 2003, Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia, J Appl Physiol (1985) source

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    Premisecitation

    Lean muscle mass is about 50% of total bodyweight in young adults and falls to about 25% by age 75-80 years.

    “Lean muscle mass generally contributes up to about 50% of total bodyweight in young adults, but decreases with age to be about 25% of total bodyweight by age 75–80 years.15”
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    • cites [15] Short, 2004, Age and aerobic exercise training effects on whole body and muscle protein metabolism, Am J Physiol Endocrinol Metab source

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

    Premisereasoning

    There is no standard definition for assessing sarcopenia.

    “No standardly used definition exists for assessment of sarcopenia, and consensus definitions based on critical analyses of large databases are being developed.”
    Quote in the paperNot a substantial claim

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    Interpretationreasoning

    Many chronic diseases can speed up the loss of muscle mass and strength, and this may be a main way chronic diseases cause physical disability.

    “Many chronic diseases, in addition to ageing, could also accelerate decrease of muscle mass and strength, and this effect could be a main underlying mechanism by which chronic diseases cause physical disability.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Existing definitions of sarcopenia cannot necessarily separate the effects of ageing on muscle loss from those of other age-associated diseases common in older people.

    “arguably, definitions of sarcopenia that have been developed cannot necessarily differentiate the effects of ageing on muscle loss independent of other age-associated disease conditions that are prevalent in older individuals.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    A 10% reduction in age-related muscle loss would save US$1.1 billion per year in US health-care costs.

    “Notwithstanding uncertainties, it has been estimated that a 10% reduction in age-related muscle loss would result in savings of US$1·1 billion per year in health-care costs in the USA.14”
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    • cites [14] Janssen, 2004, The healthcare costs of sarcopenia in the United States, J Am Geriatr Soc source

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    Premisecitation

    Skeletal muscle ATP production increases in response to exogenous insulin in people without diabetes, but this increment is reduced in people with diabetes and is related to impaired insulin response.

    “Nonetheless, skeletal muscle ATP production increases in response to exogenous insulin in people without diabetes, but this increment is reduced in individuals with diabetes and is related to impaired insulin response.52”
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    • cites [52] Stump, 2003, Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts, Proc Natl Acad Sci USA source

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    The causal link from adiposity to intramyocellular lipid deposition is unclear.

    “However, the causal link from adiposity to intramyocellular lipid deposition is unclear,”
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    Premisecitation

    Diabetes is associated with accelerated loss of muscle mass and strength; this loss is greater with longer diabetes duration or higher HbA1c and is attenuated by insulin sensitisers.

    “In both cross-sectional and longitudinal studies, accelerated loss of muscle mass and strength is recorded in individuals with diabetes, is greater with longer diabetes duration or higher HbA1c, and is attenuated by use of insulin sensitisers.36-38”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [36] Park, 2009, Excessive loss of skeletal muscle mass in older adults with type 2 diabetes, Diabetes Care source

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    • cites [38] Lee, 2011, Insulin sensitizers may attenuate lean mass loss in older men with diabetes, Diabetes Care source

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    Premisecitation

    PGC-1α gene expression is reduced in muscles of patients with type 2 diabetes and may have a role in preventing muscle atrophy.

    “PGC-1α is a transcriptional coactivator that has reduced gene expression in muscles of patients with type 2 diabetes,55 and might have a role in preventing muscle atrophy.53,56”
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    • cites [55] Patti, 2003, Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1, Proc Natl Acad Sci USA source

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    • cites [53] Sandri, 2006, PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription, Proc Natl Acad Sci USA source

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    • cites [56] Lira, 2010, PGC-1alpha regulation by exercise training and its influences on muscle function and insulin sensitivity, Am J Physiol Endocrinol Metab source

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    Interpretationreasoning

    Insulin resistance decreases stimulation of protein synthesis and increases activation of protein degradation pathways, which may lead to muscle loss in type 2 diabetes.

    “Insulin resistance results in decreased stimulation of protein synthesis pathways and increased activation of protein degradation pathways that might ultimately lead to muscle loss in type 2 diabetes (figure 1).”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Global diabetes prevalence is projected to rise exponentially, with the greatest burden in older adults over 65 years.

    “The global prevalence of diabetes is projected to rise exponentially during the next few decades, with the greatest burden in older individuals (aged >65 years).32,33”
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    • cites [32] Cowie, 2009, Full accounting of diabetes and pre-diabetes in the U.S. population in 1988–1994 and 2005–2006, Diabetes Care source

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    • cites [33] Shaw, 2010, Global estimates of the prevalence of diabetes for 2010 and 2030, Diabetes Res Clin Pract source

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    Premisecitation

    Insulin substantially stimulates muscle protein synthesis in young people but not in older people.

    “Insulin is a powerful anabolic signal and substantially stimulates muscle protein synthesis in young people but not in older people.”
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    • cites [45] Fujita, 2009, Supraphysiological hyperinsulinaemia is necessary to stimulate skeletal muscle protein anabolism in older adults: evidence of a true age-related insulin resistance of muscle protein metabolism, Diabetologia source

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    Premisecitation

    Up to 70% of adults with diabetes have difficulty with routine physical tasks, and diabetes is a potent risk factor for most geriatric syndromes.

    “Up to 70% of adults with diabetes have difficulty carrying out routine physical tasks, with lower extremity mobility limitations particularly evident, and diabetes is a potent risk factor for most geriatric syndromes.34”
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    • cites [34] Kalyani, 2010, Association of diabetes, comorbidities, and A1C with functional disability in older adults: results from the National Health and Nutrition Examination Survey (NHANES), 1999-2006, Diabetes Care source

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    Premisecitation

    In insulin resistance, suppressed insulin or IGF-1 signalling downregulates the phosphatidylinositol 3 kinase/Akt pathway, decreases protein synthesis, and phosphorylates forkhead box protein O1, which increases E3 enzymes via the ubiquitin-proteasome pathway and contributes to muscle protein degradation.

    “In insulin resistance, insulin or IGF-1 signalling is suppressed, leading to downregulation of the phosphatidylinositol 3 kinase/Akt pathway and decreased protein synthesis, as well as to forkhead box protein O1 phosphorylation. Phosphorylated forkhead box protein O1 stimulates expression of the E3 enzymes atrogin-1 and muscle ring finger-1 via increased activation of the ubiquitin-proteasome”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47] Wang, 2006, Insulin resistance accelerates muscle protein degradation: Activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling, Endocrinology source

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    Premisecitation

    Loss of height and lean body mass and increasing fat mass with ageing uncouple the relationship between BMI and obesity and attenuate associations with mortality.

    “However, loss of height and lean body mass and increasing fat mass that occur with ageing uncouple the relationship of BMI and obesity, and attenuate associations with mortality.”
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    • cites [58] Waters, 2011, Sarcopenia and obesity, Clin Geriatr Med source

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    Premisecitation

    A systematic review found that GH-treated individuals had a significant decrease in fat mass of 2.08 kg (95% CI 1.35-2.80) and a significant increase in lean body mass of 2.13 kg (95% CI 1.32-2.94).

    “A systematic review noted that individuals treated with GH had a significant decrease in fat mass (−2·08 kg, 95% CI −1·35 to −2·80 kg) and a significant increase in lean body mass (+2·13 kg, 95% CI 1·32 to 2·94 kg).”
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    • cites [96] Liu, 2007, Systematic review: the safety and efficacy of growth hormone in the healthy elderly, Ann Intern Med source

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    Interpretationcitation

    This adaptive mechanism may be impaired in older obese individuals, who may have relatively low muscle strength for their body size and an increased risk of disability.

    “However, results of studies of body composition have shown that this adaptive mechanism might be impaired in older individuals who are obese. As a result, obese individuals might have relatively low muscle strength in view of their body size and have an increased risk of disability.62”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [62] Alley, 2007, The changing relationship of obesity and disability, 1988–2004, JAMA source

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    Premisecitation

    In men, total testosterone concentrations decrease by 1% per year and bioavailable testosterone by 2% per year from age 30 years.

    “In men, total testosterone concentrations decrease by 1% per year and bioavailable testosterone by 2% per year from the age of 30 years.”
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    • cites [77] Maggio, 2011, Gonadal status and physical performance in older men, Aging Male source

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    Premisecitation

    Increased adiposity and circulating free fatty acids inhibit GH production and decrease plasma IGF-1 concentrations.

    “Increased adiposity and circulating concentrations of free fatty acids inhibit GH production and decrease plasma concentrations of IGF-1.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [93] Perrini, 2010, The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis, J Endocrinol source

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    Premisecitation

    Dihydroepiandrosterone sulphate concentrations decrease with ageing; in men aged 70-80 years they are only about 20% of peak concentrations at age 20 years.

    “Dihydroepiandrosterone sulphate is a precursor to testosterone, with concentrations that also decrease with ageing—in men aged 70–80 years, dihydroepiandrosterone sulphate concentrations are only about 20% of their peak concentrations at the age of 20 years.78”
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    Premisecitation

    A decrease in IGF-1 is associated with decreased muscle size and strength, decreased protein synthesis, and increased cell death, which in turn leads to increased visceral fat and decreased lean body mass.

    “This decrease in IGF-1 is associated with decreased muscle size and strength, decreased protein synthesis, and increased cell death,93 which in turn leads to increased visceral fat and decreased lean body mass.94”
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    Premisecitation

    GH treatment in adults with hypopituitarism and associated GH deficiency can improve body composition and increase lean body mass.

    “GH treatment in adults with hypopituitarism and associated GH deficiency can improve body composition and increase lean body mass.95”
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    Premisecitation

    Older men and women over 60 years with sarcopenic obesity have a significantly increased risk of having three or more physical disabilities compared with non-obese individuals after adjustment for age, and this association is stronger than with either sarcopenia or obesity alone.

    “Baumgartner and colleagues66 showed that both men and women older than 60 years with sarcopenic obesity had a significantly increased risk of having three or more physical disabilities compared with non-obese individuals after adjustment for age, and this association was stronger than with either sarcopenia or obesity alone.66”
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    • cites [66] Baumgartner, 2000, Body composition in healthy aging, Ann N Y Acad Sci source

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    Premisecitation

    After 6 months of androgen-deprivation therapy, older men have decreased appendicular skeletal muscle, decreased lean tissue, and increased body fat compared with untreated controls.

    “After 6 months of treatment, androgen-deprived older men have decreased appendicular skeletal muscle, decreased lean tissue, and increased body fat compared with untreated controls.79”
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    Premisecitation

    Sarcopenia and obesity can co-occur and are synergistically associated with worse functional decline and outcomes than either condition alone.

    “Sarcopenia and obesity can co-occur, and synergistically are associated with worse functional decline and outcomes than is either condition alone.70”
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    • cites [70] Stenholm, 2009, The effect of obesity combined with low muscle strength on decline in mobility in older persons: results from the InCHIANTI study, Int J Obes (Lond) source

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    Premisecitation

    Testosterone replacement is associated with respiratory and skin/subcutaneous adverse effects and with adverse cardiovascular outcomes.

    “Additionally, testosterone replacement is not without potential risks, including increased respiratory disorders (eg, cough, shortness of breath, asthma or chronic obstructive pulmonary disease (COPD) exacerbation, sleep apnoea) and skin and subcutaneous tissue disorders (eg, application site reactions, itching, erythema, foot ulcers, and increased hair growth).84”
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    Premisecitation

    Obesity alone may contribute more to lower physical function than sarcopenia alone, but this probably depends on the degree of muscle loss.

    “Findings from few studies suggest that obesity alone might contribute more to lower physical function than does sarcopenia alone, but this probably depends on the degree of muscle loss.71”
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    Premisecitation

    Sarcopenic obesity prevalence increases with each decade of age and is lower in non-Hispanic black people than in white people.

    “Generally, irrespective of definition, the prevalence increased with each decade of age and was lower in non-Hispanic black people than in white people.”
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    Premisecitation

    In healthy young and older individuals, bone and muscle tend to correlate with bodyweight, probably because gravity and inertial forces during movement stimulate mechanoreceptors in bone and muscle.

    “In healthy young and older individuals, bone and muscle tend to be correlated with bodyweight, probably because gravity and inertial forces during movement stimulate mechano-receptors in both bone and muscle that modulate the production of growth factors.61”
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    Premisecitation

    Age-related loss of muscle mass is typically offset by gains in fat mass, so bodyweight in middle age may be stable or slightly increased even though relative body fat increases compared with lean tissue.

    “Age-related loss of muscle mass is typically offset by gains in fat mass. As a result, bodyweight in men and women might be quite stable in middle age, or slightly increased even though the relative amount of body fat actually increases in comparison with lean tissue—an important step in the development of sarcopenic obesity.65”
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    • cites [65] Newman, 2005, Weight change and the conservation of lean mass in old age: the Health, Aging and Body Composition Study, Am J Clin Nutr source

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    Premisecitation

    With normalisation of thyroid concentrations, muscle mass and strength are re-established, but this can take up to 9 months.

    “With normalisation of thyroid concentrations, muscle mass and strength are re-established, but this can take up to 9 months to occur.98”
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    Premisecitation

    Resistance exercise stimulates protein synthesis and results in increased muscle mass and strength.

    “Resistance exercise stimulates protein synthesis and results in increased muscle mass and strength.121”
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    • cites [121] Cauza, 2009, Effects of progressive strength training on muscle mass in type 2 diabetes mellitus patients determined by computed tomography, Wien Med Wochenschr source

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    Premisecitation

    Decreased caloric intake and anorexia associated with cancer might contribute to muscle loss, but aggressive caloric supplementation alone cannot reverse skeletal muscle loss.

    “Although decreased caloric intake and anorexia associated with cancer might contribute to muscle loss, this is not the only factor; aggressive caloric supplementation alone cannot reverse the skeletal muscle loss.116”
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    • cites [116] Muscaritoli, 2010, Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics”, Clin Nutr source

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    Premisecitation

    Vitamin D supplementation might reduce falls and improve muscle strength, but the evidence is inconclusive.

    “Vitamin D supplementation might also have wide-ranging beneficial effects in reducing falls and improving muscle strength, but evidence is inconclusive; large randomised controlled trials are addressing this hypothesis.102”
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    • cites [102] Kalyani, 2010, Vitamin D treatment for the prevention of falls in older adults: systematic review and meta-analysis, J Am Geriatr Soc source

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    Premisecitation

    Osteoporosis is associated with loss of muscle function and mobility limitations, although the direction of this association is unclear.

    “Osteoporosis is also associated with the loss of muscle function and mobility limitations, although the direction of this association is unclear.103”
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    • cites [103] Ferrucci, 2013, Interaction between bone and muscle in older persons with mobility limitations, Curr Pharm Des

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    Premisecitation

    Several factors likely contribute to muscle loss in rheumatoid arthritis, including pro-inflammatory cytokines, reduced protein synthesis in myocytes, physical activity limitations, insulin resistance, and inadequate protein ingestion.

    “Several factors are likely to contribute to muscle loss, including the presence of pro-inflammatory cytokines in rheumatoid arthritis. Additionally, reduced protein synthesis in myocytes, physical activity limitations, insulin resistance, and inadequate protein ingestion could occur.106”
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    Premisecitation

    Patients with HIV have lower muscle strength than healthy individuals, but resistance exercise can safely increase the strength of older patients with HIV to equal that of counterparts.

    “Patients with HIV have lower muscle strength than do healthy individuals; however, resistance exercise can safely increase the strength of older patients with HIV to equal that of counterparts.119”
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    • cites [119] Souza, 2011, Effect of progressive resistance exercise on strength evolution of elderly patients living with HIV compared to healthy controls, Clinics (Sao Paulo) source

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    Premisecitation

    Tumour-induced inflammation can increase production of tumour necrosis factor alpha, interleukin 6, interferon gamma, and other cytokines, resulting in increased protein catabolism, decreased protein anabolism, insulin resistance, and lipolysis.

    “Tumour-induced inflammation can lead to increased production of tumour necrosis factor alpha, interleukin 6, interferon gamma, and other cytokines, which results in increased protein catabolism, decreased protein anabolism, insulin resistance, and lipolysis.115”
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    • cites [115] Dodson, 2011, Muscle wasting in cancer cachexia: clinical implications, diagnosis, and emerging treatment strategies, Annu Rev Med source

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    Premisecitation

    Oxandrolone has been used to treat muscle loss in HIV and other catabolic disorders, with notable improvements in muscle function and faster recovery.

    “Oxandrolone is an anabolic steroid treatment that has been used to treat muscle loss in diseases such as HIV, and also in patients with other catabolic disorders such as neuromuscular diseases, or in individuals who have had severe trauma, burn injury, or infections, with notable improvements in muscle function and faster recovery.120”
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    • cites [120] Porro, 2012, Five-year outcomes after oxandrolone administration in severely burned children: a randomized clinical trial of safety and efficacy, J Am Coll Surg source

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  • May combine two claims.

    Premisecitation

    Glucocorticoids inhibit protein synthesis and stimulate protein degradation in skeletal muscles; IGF-1 is decreased and myostatin is increased.

    “Glucocorticoids inhibit protein synthesis and stimulate protein degradation in skeletal muscles. IGF-1 is decreased and myostatin is increased.99”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [99] Schakman, 2008, Mechanisms of glucocorticoid-induced myopathy, J Endocrinol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Resistance exercise is effective and safe to prevent muscle loss even in old (mean age 87 years) and frail individuals, potentially by also decreasing skeletal muscle apoptosis and improving mitochondrial function.

    “Resistance exercise is effective and safe to prevent muscle loss even in old (mean age 87 years) and frail individuals, potentially by also decreasing skeletal muscle apoptosis and improving mitochondrial function.123”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [123] Fiatarone, 1994, Exercise training and nutritional supplementation for physical frailty in very elderly people, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Muscle loss may also occur in rheumatoid arthritis, peripheral arterial disease, COPD, congestive heart failure, advanced kidney disease, cirrhosis, cancer, and HIV.

    “Muscle loss might also occur in other disease states, including rheumatoid arthritis, peripheral arterial disease, COPD, congestive heart failure, advanced kidney disease, cirrhosis, cancer, and HIV, which we describe briefly here;”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    The increase in muscle strength after resistance exercise occurs almost immediately, after a few days, and much before a noticeable increase in muscle mass, suggesting that the primary effect of exercise might be on muscle quality rather than hypertrophy.

    “The increase in muscle strength occurs almost immediately, after a few days of exercise, and much before a noticeable increase in muscle mass, suggesting that the primary effect of exercise might not be on hypertrophy but rather on muscle quality.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [121] Cauza, 2009, Effects of progressive strength training on muscle mass in type 2 diabetes mellitus patients determined by computed tomography, Wien Med Wochenschr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In patients with severe thyrotoxicosis, muscle mass can be reduced by up to 20% and muscle strength by 40%.

    “Muscle mass can be reduced by up to 20% and muscle strength by 40% in patients with severe thyrotoxicosis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [98] Nørrelund, 1999, Muscle mass and function in thyrotoxic patients before and during medical treatment, Clin Endocrinol (Oxf) source

      Not checked in the free run.

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

    Premisenone given

    Exercise has clear beneficial effects on muscle health.

    “Contrary to the clear beneficial effects of exercise on muscle health”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Aerobic and resistance exercise enhance glycemic control and insulin sensitivity in type 2 diabetes patients.

    “findings from several studies have shown the benefits of exercise (aerobic and resistance) for improvement of glucose metabolism and insulin sensitivity in people with type 2 diabetes.130”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [130] Boulé, 2001, Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials, JAMA source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Increased contractile activity promotes oxidative fibre type transformation, PGC-1α expression, mitochondrial biogenesis, and muscle protein synthesis, and could lead to reduced inflammation and oxidative stress.

    “In parallel, increased contractile activity promotes oxidative fibre type transformation, PGC-1α expression, mitochondrial biogenesis, and muscle protein synthesis, and could lead to reduced inflammation and oxidative stress.56”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [56] Lira, 2010, PGC-1alpha regulation by exercise training and its influences on muscle function and insulin sensitivity, Am J Physiol Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In older women, losing roughly 5% of body weight enhanced insulin sensitivity, fat distribution, and muscle lipid content, maintained thigh muscle, and caused only a small drop in appendicular lean mass.

    “Moderate weight loss of about 5% in older women was found to improve insulin resistance, fat distribution, and muscle lipid infiltration, and preserve thigh muscle mass, with only a slight decrease in appendicular lean mass.136”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [136] Mazzali, 2006, Interrelations between fat distribution, muscle lipid content, adipocytokines, and insulin resistance: effect of moderate weight loss in older women, Am J Clin Nutr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Among sarcopenic older adults, taking 16 g daily of essential amino acids was linked to greater lean mass at 6 and 18 months and better insulin sensitivity.

    “In preliminary studies of older men and women with sarcopenia, oral supplementation with 16 g per day of essential aminoacids was associated with increased lean mass at 6 months and a further increase at 18 months, along with improved insulin sensitivity.135”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [135] Solerte, 2008, Nutritional supplements with oral amino acid mixtures increases whole-body lean mass and insulin sensitivity in elderly subjects with sarcopenia, Am J Cardiol source

      Not checked in the free run.

53 of 53

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Authors
Kalyani, R. R., Corriere, M., & Ferrucci, L.
Affiliations
  • Johns Hopkins University (US)
  • National Institute on Aging (US)
ORCID
Venue
The Lancet Diabetes & Endocrinology
Publisher
Elsevier BV
Published
2014-10
Volume
2
Issue
10
Pages
819-829
ISSN
2213-8587 (ISSN-L)
DOI
10.1016/s2213-8587(14)70034-8
PMC
PMC4156923
OpenAlex
W2139789661
Semantic Scholar
3c56fce30ecb0e77c93458bf0fbc85a0747736ea
Cited by
1,102
References
145
Citations by year
2026: 76 · 2025: 117 · 2024: 110 · 2023: 133 · 2022: 128 · 2021: 114 · 2020: 106 · 2019: 82 · 2018: 72 · 2017: 79 · 2016: 51 · 2015: 18 · 2014: 15
FWCI
6.38
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Lancet Diabetes & Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • US National Institute of Diabetes and Digestive and Kidney Diseases (K23-DK093583, T32-DK062707)
  • Johns Hopkins Older Americans Independence Center (P30-AG021334)
Topics
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Keywords
sarcopenia, muscle mass loss, muscle strength, aging, diabetes mellitus, obesity, chronic disease, physical disability, functional decline, sarcopenia treatment, older adults
MeSH terms
Endocrine System Diseases, Humans, Male, Obesity, Diabetes Complications, Sarcopenia

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 2026-10-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.

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