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

In the paper

“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.”

What the sources say

• Supported

  The Epidemiology section (page unavailable) says reduced muscle mass is highly prevalent in older people and increases with age; Muscle Aging describes a substantial age-related decline in strength. Sarcopenia and Disability (page unavailable) links sarcopenia to disability and possible increased mortality, and reports that weakness predicts mortality more strongly than muscle mass. (LLM, conf=0.89)

  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 yetcites [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

In the paper

“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”

What the sources say

• Supported

  The section “Abnormalities in GH/IGF1 signaling and age-related muscle mass wasting” states that age-associated reductions in GH and IGF1 are associated with decreased muscle size and strength, diminished protein synthesis, and increased cell apoptosis. This supports the clause attached to citation 93. The visceral-fat and lean-body-mass clause is attached to citation 94, so it is not assessed against this source. (LLM, conf=0.92)

  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
• Not checked yetcites [94] Nass, 2002, Impact of the GH-cortisol ratio on the age-dependent changes in body composition, Growth Horm IGF Res source

In the paper

“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.”

In the paper

“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;”

In the paper

“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”

What the sources say

• Not checked yetcites [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
• Not checked yetcites [2] Lauretani, 2003, Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia, J Appl Physiol (1985) source

In the paper

“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”

What the sources say

• Not checked yetcites [15] Short, 2004, Age and aerobic exercise training effects on whole body and muscle protein metabolism, Am J Physiol Endocrinol Metab source

In the paper

“No standardly used definition exists for assessment of sarcopenia, and consensus definitions based on critical analyses of large databases are being developed.”

In the paper

“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 the paper

“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.”

In the paper

“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”

What the sources say

• Not checked yetcites [14] Janssen, 2004, The healthcare costs of sarcopenia in the United States, J Am Geriatr Soc source

In the paper

“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”

What the sources say

• Not checked yetcites [52] Stump, 2003, Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts, Proc Natl Acad Sci USA source

In the paper

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

In the paper

“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”

What the sources say

• Not checked yetcites [36] Park, 2009, Excessive loss of skeletal muscle mass in older adults with type 2 diabetes, Diabetes Care source
• Not checked yetcites [37] Park, 2007, Accelerated loss of skeletal muscle strength in older adults with type 2 diabetes: the health, aging, and body composition study, Diabetes Care source
• Not checked yetcites [38] Lee, 2011, Insulin sensitizers may attenuate lean mass loss in older men with diabetes, Diabetes Care source

In the paper

“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”

What the sources say

• Not checked yetcites [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
• Not checked yetcites [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
• Not checked yetcites [56] Lira, 2010, PGC-1alpha regulation by exercise training and its influences on muscle function and insulin sensitivity, Am J Physiol Endocrinol Metab source

In the paper

“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).”

In the paper

“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”

What the sources say

• Not checked yetcites [32] Cowie, 2009, Full accounting of diabetes and pre-diabetes in the U.S. population in 1988–1994 and 2005–2006, Diabetes Care source
• Not checked yetcites [33] Shaw, 2010, Global estimates of the prevalence of diabetes for 2010 and 2030, Diabetes Res Clin Pract source

In the paper

“Insulin is a powerful anabolic signal and substantially stimulates muscle protein synthesis in young people but not in older people.”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [47] Wang, 2006, Insulin resistance accelerates muscle protein degradation: Activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling, Endocrinology source

In the paper

“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.”

What the sources say

• Not checked yetcites [58] Waters, 2011, Sarcopenia and obesity, Clin Geriatr Med source

In the paper

“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).”

What the sources say

• Not checked yetcites [96] Liu, 2007, Systematic review: the safety and efficacy of growth hormone in the healthy elderly, Ann Intern Med source

In the paper

“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”

What the sources say

• Not checked yetcites [62] Alley, 2007, The changing relationship of obesity and disability, 1988–2004, JAMA source

In the paper

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

What the sources say

• Not checked yetcites [77] Maggio, 2011, Gonadal status and physical performance in older men, Aging Male source

In the paper

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

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [78] Labrie, 1997, Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging, J Clin Endocrinol Metab source

In the paper

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

What the sources say

• Not checked yetcites [95] Salomon, 1989, The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency, N Engl J Med source

In the paper

“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”

What the sources say

• Not checked yetcites [66] Baumgartner, 2000, Body composition in healthy aging, Ann N Y Acad Sci source

In the paper

“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”

What the sources say

• Not checked yetcites [79] Boxer, 2005, The effect of 6 months of androgen deprivation therapy on muscle and fat mass in older men with localized prostate cancer, Aging Male source

In the paper

“Sarcopenia and obesity can co-occur, and synergistically are associated with worse functional decline and outcomes than is either condition alone.70”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [84] Basaria, 2010, Adverse events associated with testosterone administration, N Engl J Med source

In the paper

“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”

What the sources say

• Not checked yetcites [71] Bouchard, 2009, Sarcopenic/obesity and physical capacity in older men and women: data from the Nutrition as a Determinant of Successful Aging (NuAge)-the Quebec longitudinal Study, Obesity (Silver Spring) source

In the paper

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

What the sources say

• Not checked yetcites [69] Batsis, 2013, Variation in the prevalence of sarcopenia and sarcopenic obesity in older adults associated with different research definitions: dual-energy X-ray absorptiometry data from the National Health and Nutrition Examination Survey 1999–2004, J Am Geriatr Soc source

In the paper

“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”

What the sources say

• Not checked yetcites [61] Russo, 2000, True osteoporosis and frailty-related osteopenia: two different clinical entities, J Am Geriatr Soc source

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

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

What the sources say

• Not checked yetcites [98] Nørrelund, 1999, Muscle mass and function in thyrotoxic patients before and during medical treatment, Clin Endocrinol (Oxf) source

In the paper

“Resistance exercise stimulates protein synthesis and results in increased muscle mass and strength.121”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [102] Kalyani, 2010, Vitamin D treatment for the prevention of falls in older adults: systematic review and meta-analysis, J Am Geriatr Soc source

In the paper

“Osteoporosis is also associated with the loss of muscle function and mobility limitations, although the direction of this association is unclear.103”

What the sources say

• Not checked yetcites [103] Ferrucci, 2013, Interaction between bone and muscle in older persons with mobility limitations, Curr Pharm Des

In the paper

“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”

What the sources say

• Not checked yetcites [106] de Oliveira Nunes Teixeira, 2013, Muscle wasting in collagen-induced arthritis and disuse atrophy, Exp Biol Med (Maywood) source

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [115] Dodson, 2011, Muscle wasting in cancer cachexia: clinical implications, diagnosis, and emerging treatment strategies, Annu Rev Med source

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

“Glucocorticoids inhibit protein synthesis and stimulate protein degradation in skeletal muscles. IGF-1 is decreased and myostatin is increased.99”

What the sources say

• Not checked yetcites [99] Schakman, 2008, Mechanisms of glucocorticoid-induced myopathy, J Endocrinol source

In the paper

“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”

What the sources say

• Not checked yetcites [123] Fiatarone, 1994, Exercise training and nutritional supplementation for physical frailty in very elderly people, N Engl J Med source

In the paper

“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;”

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“Muscle mass can be reduced by up to 20% and muscle strength by 40% in patients with severe thyrotoxicosis.”

What the sources say

• Not checked yetcites [98] Nørrelund, 1999, Muscle mass and function in thyrotoxic patients before and during medical treatment, Clin Endocrinol (Oxf) source

In the paper

“Contrary to the clear beneficial effects of exercise on muscle health”

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [56] Lira, 2010, PGC-1alpha regulation by exercise training and its influences on muscle function and insulin sensitivity, Am J Physiol Endocrinol Metab source

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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