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1.  Lack of exercise is a major cause of chronic diseases 
Comprehensive Physiology  2012;2(2):1143-1211.
Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause vs. treatment; physical activity and inactivity mechanisms differ; gene-environment interaction [including aerobic training adaptations, personalized medicine, and co-twin physical activity]; and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [Accelerated biological aging/premature death, low cardiorespiratory fitness (VO2max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, non-alcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, preeclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases]. The article ends with consideration of deterioration of risk factors in longer-term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life.
doi:10.1002/cphy.c110025
PMCID: PMC4241367  PMID: 23798298
2.  Clinical definition of sarcopenia 
Summary
Sarcopenia is a condition characterized by loss of skeletal muscle mass and function. Although it is primarily a disease of the elderly, its development may be associated with conditions that are not exclusively seen in older persons. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength and it is strictly correlated with physical disability, poor quality of life and death. Risk factors for sarcopenia include age, gender and level of physical activity. In conditions such as malignancy, rheumatoid arthritis and aging, lean body mass is lost while fat mass may be preserved or even increased. The loss in muscle mass may be associated with increased body fat so that despite normal weight there is marked weakness, this is a condition called sarcopenic obesity. There is an important correlation between inactivity and losses of muscle mass and strength, this suggests that physical activity should be a protective factor for the prevention but also the management of sarcopenia. Furthermore one of the first step to be taken for a person with sarcopenia or clinical frailty is to ensure that the sarcopenic patient is receiving correct and sufficient nutrition. Sarcopenia has a greater effect on survival. It should be important to prevent or postpone as much as possible the onset of this condition, to enhance survival and to reduce the demand for long-term care. Interventions for sarcopenia need to be developed with most attention on exercise and nutritional interventions.
PMCID: PMC4269139  PMID: 25568649
sarcopenia; epidemiology; weakness; sarcopenic obesity
3.  Sarcopenia, obesity, and natural killer cell immune senescence in aging: Altered cytokine levels as a common mechanism 
Aging (Albany NY)  2012;4(8):535-546.
Human aging is characterized by both physical and physiological frailty. A key feature of frailty, sarcopenia is the age-associated decline in skeletal muscle mass, strength, and endurance that characterize even the healthy elderly. Increases in adiposity, particularly in visceral adipose tissue, are almost universal in aging individuals and can contribute to sarcopenia and insulin resistance by increasing levels of inflammatory cytokines known collectively as adipokines. Aging also is associated with declines in adaptive and innate immunity, known as immune senescence, which are risk factors for cancer and all-cause mortality. The cytokine interleukin-15 (IL-15) is highly expressed in skeletal muscle tissue and declines in aging rodent models. IL-15 inhibits fat deposition and insulin resistance, is anabolic for skeletal muscle in certain situations, and is required for the development and survival of natural killer (NK) lymphocytes. We review the effect that adipokines and myokines have on NK cells, with special emphasis on IL-15. We posit that increased adipokine and decreased IL-15 levels during aging constitute a common mechanism for sarcopenia, obesity, and immune senescence.
PMCID: PMC3461341  PMID: 22935594
Skeletal muscle; adipose tissue; Sarcopenia; obesity; immunity; natural killer lymphocytes; aging
4.  Osteosarcopenic obesity: the role of bone, muscle, and fat on health 
Osteopenia/osteoporosis, sarcopenia, and obesity are commonly observed in the process of aging, and recent evidence suggests a potential interconnection of these syndromes with common pathophysiology. The term osteosarcopenic obesity has been coined to describe the concurrent appearance of obesity in individuals with low bone and muscle mass. Although our understanding of osteosarcopenic obesity’s etiology, prevalence, and consequences is extremely limited, it is reasonable to infer its negative impact in a population that is aging in an obesogenic environment. It is likely that these individuals will present with poorer clinical outcomes caused by the cascade of metabolic abnormalities associated with these changes in body composition. Clinical outcomes include but are not limited to increased risk of fractures, impaired functional status (including activities of daily living), physical disability, insulin resistance, increased risk of infections, increased length of hospital stay, and reduced survival. These health outcomes are likely to be worse when compared to individuals with obesity, sarcopenia, or osteopenia/osteoporosis alone. Interventions that utilize resistance training exercise in conjunction with increased protein intake appear to be promising in their ability to counteract osteosarcopenic obesity.
doi:10.1007/s13539-014-0146-x
PMCID: PMC4159494  PMID: 24740742
Osteopenia/osteoporosis; Sarcopenia; Obesity; Body composition
5.  Effects of an Oral Ghrelin Mimetic on Body Composition and Clinical Outcomes in Healthy Older Adults: A Randomized, Controlled Trial 
Annals of internal medicine  2008;149(9):601-611.
Background
Growth hormone (GH) secretion and muscle mass decline from mid-puberty throughout life culminating in sarcopenia, frailty, decreased function and loss of independence.
Objective
Determine if an oral ghrelin mimetic (MK-677) would enhance GH secretion into the young adult range without serious adverse effects, prevent the decline of fat-free mass (FFM), and decrease abdominal visceral fat (AVF) in healthy older adults.
Design
Two-year, double-blind, randomized, placebo-controlled, modified-crossover clinical trial.
Setting
General Clinical Research Center study performed at a University Hospital.
Participants
Sixty-five healthy men and women (on or off hormone replacement therapy) ages 60-81.
Intervention
Oral administration of MK-677 (25 mg) or placebo once daily.
Measurements
Growth hormone and insulin-like growth factor-I (IGF-I); FFM and AVF were the primary endpoints after one year of treatment. Other endpoints: weight, fat mass, insulin sensitivity, lipid and cortisol levels, bone mineral density, limb lean and fat mass, isokinetic strength, function and quality of life; all endpoints were assessed at baseline and every 6 months.
Limitations
Study design (duration and subject number) not sufficient to evaluate functional endpoints in healthy elderly
Results
Daily MK-677 significantly increased GH and IGF-I levels to those of healthy young adults without serious adverse effects. With placebo, mean (95% Cl) FFM decreased -0.5 (-1.1 to 0.2) kg, however, FFM increased 1.1 (0.7 to 1.5) kg with MK-677 (P<0.001, MK-677 vs. placebo); body cell mass as reflected by intracellular water decreased -1.0 (-2.1 to 0.2) kg with placebo, but increased 0.8 (-0.1 to 1.6) kg with MK-677 (P=0.021). There were no significant differences in AVF or total fat mass. However, the average increase in limb fat in the MK-677 group (1.1 kg) was greater than with placebo (0.24 kg); P=0.001. Body weight increased 0.8 (-0.3 to 1.8) kg with placebo and 2.7 (2.0 to 3.5) kg with MK-677 (P=0.003). Fasting blood glucose increased an average of 0.3 mmol/L (5 mg/dL) with MK-677 (P=0.015) and insulin sensitivity declined. The most frequent side effects were an increase in appetite that subsided within a few months and transient, mild lower extremity edema and muscle pain. Low density lipoprotein cholesterol decreased -0.14 (-0.27 to -0.01) mmol/L [-5.4 (-10.4 to -0.4) mg/dL] with MK-677 (P=0.026); there were no differences in total or high density lipoprotein cholesterol. Cortisol increased 47 (28 to 71) nmol/L [1.7 (1.0 to 2.6 µg/dL)] with MK-677 (P=0.020). Changes in bone mineral density consistent with increased bone remodeling occurred in MK-677-treated subjects. Increased FFM did not result in changes in strength or function. Two-year exploratory analyses confirmed the 1-year results.
Conclusions
The ghrelin mimetic MK-677 enhanced pulsatile GH secretion and significantly increased FFM over 12 months and was generally well tolerated. Long-term functional, and ultimately pharmaco-economic, studies in elderly adults are indicated.
PMCID: PMC2757071  PMID: 18981485
Ghrelin; ghrelin mimetic; body composition; aging; sarcopenia; frailty; healthspan; growth hormone; growth hormone secretagogue
6.  Similarities in Acquired Factors Related to Postmenopausal Osteoporosis and Sarcopenia 
Journal of Osteoporosis  2011;2011:536735.
Postmenopausal population is at increased risk of musculoskeletal impairments. Sarcopenia and osteoporosis are associated with significant morbidity and social and health-care costs. These two conditions are uniquely linked with similarities in pathophysiology and diagnostic methods. Uniform diagnostic criteria for sarcopenia are still evolving. Postmenopausal sarcopenia and osteoporosis share many environmental risk- and preventive factors. Moreover, geriatric frailty syndrome may result from interaction of osteoporosis and sarcopenia and may lead to increased mortality. The present paper reviews the factors in evolution of postmenopausal sarcopenia and osteoporosis.
doi:10.4061/2011/536735
PMCID: PMC3166567  PMID: 21904688
7.  Sarcopenia Exacerbates Obesity-Associated Insulin Resistance and Dysglycemia: Findings from the National Health and Nutrition Examination Survey III 
PLoS ONE  2010;5(5):e10805.
Background
Sarcopenia often co-exists with obesity, and may have additive effects on insulin resistance. Sarcopenic obese individuals could be at increased risk for type 2 diabetes. We performed a study to determine whether sarcopenia is associated with impairment in insulin sensitivity and glucose homeostasis in obese and non-obese individuals.
Methodology
We performed a cross-sectional analysis of National Health and Nutrition Examination Survey III data utilizing subjects of 20 years or older, non-pregnant (N = 14,528). Sarcopenia was identified from bioelectrical impedance measurement of muscle mass. Obesity was identified from body mass index. Outcomes were homeostasis model assessment of insulin resistance (HOMA IR), glycosylated hemoglobin level (HbA1C), and prevalence of pre-diabetes (6.0≤ HbA1C<6.5 and not on medication) and type 2 diabetes. Covariates in multiple regression were age, educational level, ethnicity and sex.
Principal Findings
Sarcopenia was associated with insulin resistance in non-obese (HOMA IR ratio 1.39, 95% confidence interval (CI) 1.26 to 1.52) and obese individuals (HOMA-IR ratio 1.16, 95% CI 1.12 to 1.18). Sarcopenia was associated with dysglycemia in obese individuals (HbA1C ratio 1.021, 95% CI 1.011 to 1.043) but not in non-obese individuals. Associations were stronger in those under 60 years of age. We acknowledge that the cross-sectional study design limits our ability to draw causal inferences.
Conclusions
Sarcopenia, independent of obesity, is associated with adverse glucose metabolism, and the association is strongest in individuals under 60 years of age, which suggests that low muscle mass may be an early predictor of diabetes susceptibility. Given the increasing prevalence of obesity, further research is urgently needed to develop interventions to prevent sarcopenic obesity and its metabolic consequences.
doi:10.1371/journal.pone.0010805
PMCID: PMC3279294  PMID: 22421977
8.  Effects of Growth Hormone and Pioglitazone in Viscerally Obese Adults with Impaired Glucose Tolerance: A Factorial Clinical Trial 
PLoS Clinical Trials  2007;2(5):e21.
Objective:
Recombinant human growth hormone (GH) and pioglitazone (PIO) in abdominally obese adults with impaired glucose tolerance were evaluated under the hypothesis that the combination attenuates GH-induced increases in glucose concentrations, reduces visceral adipose tissue (VAT), and improves insulin sensitivity over time.
Design:
Randomized, double-blind, placebo-controlled, 2 × 2 factorial design.
Setting:
Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States.
Participants:
62 abdominally obese adults aged 40–75 with impaired glucose tolerance.
Interventions:
GH (8 μg/kg/d, or placebo) and pioglitazone (30 mg/d, or placebo) for 40 wk.
Outcome Measures:
Baseline and after 40 wk of treatment, VAT content was quantified by CT scan, glucose tolerance was assessed using a 75-g oral glucose tolerance test, and insulin sensitivity was measured using steady-state plasma glucose levels obtained during insulin suppression test.
Results:
Baseline: body mass index (BMI), plasma glucose, and visceral fat content were similar. 40 wk: visceral fat area declined 23.9 ± 7.4 cm2 in GH group, mean difference from placebo: −28.1 cm2 (95% CI −49.9 to −6.3 cm2; p = 0.02). Insulin resistance declined 52 ± 11.8 mg/dl with PIO, mean difference from placebo of −58.8 mg/dl (95% CI −99.7 to −18.0 mg/dl; p = 0.01). VAT and SSPG declined with GH and PIO combined, mean differences from placebo of −31.4 cm2 (95% CI −56.5 cm2 to −6.3 cm2; p = 0.02) and −55.3 mg/dl (95% CI −103.9 to −6.7 mg/dl; p = 0.02), respectively. Fasting plasma glucose increased transiently in GH group. No significant changes in BMI were observed.
Conclusions:
Addition of PIO to GH attenuated the short-term diabetogenic effect of GH; the drug combination reduced VAT and insulin resistance over time. GH plus PIO may have added benefit on body composition and insulin sensitivity in the metabolic syndrome.
Editorial Commentary
Background: People who are overweight are at higher risk of developing type 2 diabetes, particularly if they have impaired glucose tolerance (IGT). When an individual has IGT, their cells are not able to respond properly to insulin in the blood, which means that blood sugar levels can remain high, and fat cells do not take up fatty acids from blood at the rate they should. The term prediabetes is often used to refer to these linked characteristics. However, if such individuals are able to lose weight they can reduce their chances of becoming diabetic in the future. In particular, loss of a particular type of fat, the visceral fat (packed in around the internal organs, as opposed to fat immediately under the skin), is thought to be beneficial for people at risk of developing type 2 diabetes. Some researchers have suggested that giving human growth hormone (GH) to people who are overweight might help reduce their levels of visceral fat. At the same time, drugs known as thiazolidinediones are currently used, in combination with other drugs, diet, and exercise, as a treatment for type 2 diabetes. The researchers carrying out this study wanted to find out whether combining treatment with human GH and a thiazolidinedione, pioglitazone (PIO), would reduce levels of visceral fat and improve glucose metabolism in overweight adults with IGT. The researchers specifically planned to compare the changes in these primary outcomes amongst people receiving both human GH and PIO for 40 weeks with the changes in individuals receiving placebo only; additional comparisons were also done for individuals receiving either drug alone, as compared to placebo.
What this trial shows: A total of 76 participants were randomized and received the treatment allocated to them, but only 62 participants were included in the final analyses due to losses to follow-up. The primary outcomes being compared at baseline and after 40 weeks of treatment were the change in visceral fat levels and change in individuals' sensitivity to insulin. Individuals receiving GH experienced a drop in visceral fat area over the 40 weeks of the trial, as compared to placebo, whilst PIO alone did not seem to have an effect on visceral fat area. Individuals receiving both GH and PIO, however, also showed a decrease in visceral fat area. When examining the effect on insulin resistance, GH alone did not seem to have an effect on the ability to respond to insulin. However, administration of PIO alone did bring about a decrease in insulin resistance levels, as compared to placebo, and individuals receiving both GH and PIO together also experienced a drop in insulin resistance. The trial was not designed to detect statistically significant differences in side effects between the groups studied, but some side effects, such as build-up of fluid in the limbs and joint stiffness, seemed to be more common in the groups receiving drug treatment than in the placebo group.
Strengths and limitations: Although the trial was small, enough participants were recruited to detect statistically significant changes in the primary outcomes. Strengths of the trial include the use of appropriate techniques to conceal the randomization sequence from investigators recruiting participants into the trial and blinding of both participants and investigators to the treatments that an individual would receive. However, one limitation includes the fact that the likelihood of developing diabetes was not directly measured as an outcome in this trial, and it is therefore not possible to conclude from these results that administration of GH, PIO, or both combined, will help prevent diabetes amongst overweight people with IGT. Finally, this trial compared the drug interventions directly with placebo and not with behavioral interventions such as diet and exercise, which are normally recommended for the prevention of diabetes amongst overweight people. It would be important to further investigate the efficacy, harms, and costs of these drugs directly against nondrug interventions before making any recommendations about their clinical use.
Contribution to the evidence: Other studies have shown that PIO administration has beneficial effects on insulin sensitivity in people with type 2 diabetes. This study adds evidence confirming that PIO is likely to have similar effects in people who are not diabetic but who are overweight and who have IGT. The study also adds data regarding the effect of PIO and GH combined in such populations; giving both drugs together seemed to have beneficial effects on visceral fat area and insulin sensitivity, as compared to placebo.
doi:10.1371/journal.pctr.0020021
PMCID: PMC1865086  PMID: 17479164
9.  Insulin Responsiveness in Metabolic Syndrome after Eight Weeks of Cycle Training 
Introduction
Insulin resistance in obesity is decreased after successful diet and exercise. Aerobic exercise training alone was evaluated as an intervention in subjects with the metabolic syndrome.
Methods
Eighteen non-diabetic, sedentary subjects, eleven with the metabolic syndrome, participated in eight weeks of increasing intensity stationary cycle training.
Results
Cycle training without weight loss did not change insulin resistance in metabolic syndrome subjects or sedentary control subjects. Maximal oxygen consumption (VO2max), activated muscle AMP-dependent kinase, and muscle mitochondrial marker ATP synthase all increased. Strength, lean body mass, and fat mass did not change. Activated mammalian target of rapamycin was not different after training. Training induced a shift in muscle fiber composition in both groups but in opposite directions. The proportion of 2x fibers decreased with a concomitant increase in 2a mixed fibers in the control subjects, but in metabolic syndrome, 2x fiber proportion increased and type 1 fibers decreased. Muscle fiber diameters increased in all three fiber types in metabolic syndrome subjects. Muscle insulin receptor expression increased in both groups and GLUT4 expression increased in the metabolic syndrome subjects. Excess phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser337 in metabolic syndrome muscle tended to increase further after training in spite of a decrease in total IRS-1.
Conclusion
In the absence of weight loss, cycle training of metabolic syndrome subjects resulted in enhanced mitochondrial biogenesis, and increased expression of insulin receptors and GLUT4 in muscle, but did not decrease the insulin resistance. The failure for the insulin signal to proceed past IRS-1 tyrosine phosphorylation may be related to excess serine phosphorylation at IRS-1 Ser337 and this is not ameliorated by eight weeks of endurance exercise training.
doi:10.1249/MSS.0b013e31829a6ce8
PMCID: PMC3800492  PMID: 23669880
insulin resistance; metabolic syndrome; euglycemic clamp; exercise training
10.  Effects of 12 Weeks of Combined Exercise Training on Visfatin and Metabolic Syndrome Factors in Obese Middle-Aged Women 
Visfatin is a highly expressed protein with insulin-like functions located predominantly in visceral adipose tissue and has been linked to obesity and increased health risks. The purpose of this study was to examine the effects of 12 weeks of combined exercise training on visfatin and metabolic syndrome factors in obese middle-aged women. Subjects were randomly assigned to either a training (n = 10) or control (n = 10) group. The training group exercised for 1 hour, 3 days per week during the 12 week supervised training program. The training program included 3 sets of 10 repetition maximum (10RM) resistance exercise as well as aerobic exercise at an intensity of 60-70% of their heart rate reserve (HRR). The control group was asked to maintain their normal daily activities. Two-way (group X time) repeated measured analysis of variance revealed no significant main effects, but there was a significant group X time interaction for the following variables: body weight (p < 0.01), percent body fat (% fat) (p < 0.01), waist hip ratio (WHR) (p < 0.01), diastolic blood pressure (DBP) (p < 0.05), fasting glucose level (p < 0.01), triglyceride levels (TG) (p < 0.01), high density lipoprotein cholesterol levels (HDL-C) (p < 0.05), and visfatin (p < 0.01). In conclusion, the 12 week combined resistance and aerobic training program used in this study was very effective for producing significant benefits to body composition and metabolic syndrome factors, as well as lowering visfatin levels in these obese middle-aged women.
Key pointsRecent studies have linked visfatin to obesity and increased health risks.The study was done to investigate the effects of 12 weeks of combined exercise training on visfatin and metabolic syndrome factors in obese middle-aged women.The exercise program used in this study was found to be very effective for lowering visfatin levels in obese middle-aged women.
PMCID: PMC3737906  PMID: 24149317
Metabolic syndrome; combined resistance; aerobic exercise; visfatin
11.  Novel Intriguing Strategies Attenuating to Sarcopenia 
Journal of Aging Research  2012;2012:251217.
Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and, often, frailty. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. Resistance training combined with amino acid-containing supplements is often utilized to prevent age-related muscle wasting and weakness. In this review, we summarize more recent therapeutic strategies (myostatin or proteasome inhibition, supplementation with eicosapentaenoic acid (EPA) or ursolic acid, etc.) for counteracting sarcopenia. Myostatin inhibitor is the most advanced research with a Phase I/II trial in muscular dystrophy but does not try the possibility for attenuating sarcopenia. EPA and ursolic acid seem to be effective as therapeutic agents, because they attenuate the degenerative symptoms of muscular dystrophy and cachexic muscle. The activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in skeletal muscle by exercise and/or unknown supplementation would be an intriguing approach to attenuating sarcopenia. In contrast, muscle loss with age may not be influenced positively by treatment with a proteasome inhibitor or antioxidant.
doi:10.1155/2012/251217
PMCID: PMC3303581  PMID: 22500226
12.  Frailty syndrome: an overview 
Frailty is a common and important geriatric syndrome characterized by age-associated declines in physiologic reserve and function across multiorgan systems, leading to increased vulnerability for adverse health outcomes. Two major frailty models have been described in the literature. The frailty phenotype defines frailty as a distinct clinical syndrome meeting three or more of five phenotypic criteria: weakness, slowness, low level of physical activity, self-reported exhaustion, and unintentional weight loss. The frailty index defines frailty as cumulative deficits identified in a comprehensive geriatric assessment. Significant progress has recently been made in understanding the pathogenesis of frailty. Chronic inflammation is likely a key pathophysiologic process that contributes to the frailty syndrome directly and indirectly through other intermediate physiologic systems, such as the musculoskeletal, endocrine, and hematologic systems. The complex multifactorial etiologies of frailty also include obesity and specific diseases. Major clinical applications include risk assessment and stratification. This can be applied to the elderly population in the community and in a variety of care settings. Frailty may also be useful for risk assessment in surgical patients and those with cardiovascular diseases, cancer, or human immunodeficiency virus infection, as well as for assessment of vaccine effectiveness in older adults. Currently, exercise and comprehensive geriatric interdisciplinary assessment and treatment are key interventions for frailty. As understanding of the biologic basis and complexity of frailty further improves, more effective and targeted interventional strategies and innovative geriatric-care models will likely be developed.
doi:10.2147/CIA.S45300
PMCID: PMC3964027  PMID: 24672230
frailty; inflammation; IL-6; aging; older adults
13.  Global Transcript Profiles of Fat in Monozygotic Twins Discordant for BMI: Pathways behind Acquired Obesity  
PLoS Medicine  2008;5(3):e51.
Background
The acquired component of complex traits is difficult to dissect in humans. Obesity represents such a trait, in which the metabolic and molecular consequences emerge from complex interactions of genes and environment. With the substantial morbidity associated with obesity, a deeper understanding of the concurrent metabolic changes is of considerable importance. The goal of this study was to investigate this important acquired component and expose obesity-induced changes in biological pathways in an identical genetic background.
Methods and Findings
We used a special study design of “clonal controls,” rare monozygotic twins discordant for obesity identified through a national registry of 2,453 young, healthy twin pairs. A total of 14 pairs were studied (eight male, six female; white), with a mean ± standard deviation (SD) age 25.8 ± 1.4 y and a body mass index (BMI) difference 5.2 ± 1.8 kg/m2. Sequence analyses of mitochondrial DNA (mtDNA) in subcutaneous fat and peripheral leukocytes revealed no aberrant heteroplasmy between the co-twins. However, mtDNA copy number was reduced by 47% in the obese co-twin's fat. In addition, novel pathway analyses of the adipose tissue transcription profiles exposed significant down-regulation of mitochondrial branched-chain amino acid (BCAA) catabolism (p < 0.0001). In line with this finding, serum levels of insulin secretion-enhancing BCAAs were increased in obese male co-twins (9% increase, p = 0.025). Lending clinical relevance to the findings, in both sexes the observed aberrations in mitochondrial amino acid metabolism pathways in fat correlated closely with liver fat accumulation, insulin resistance, and hyperinsulinemia, early aberrations of acquired obesity in these healthy young adults.
Conclusions
Our findings emphasize a substantial role of mitochondrial energy- and amino acid metabolism in obesity and development of insulin resistance.
Leena Peltonen and colleagues uncover the metabolic changes that result from obesity through an analysis of genetically identical twin pairs in which one was obese and the other was not.
Editors' Summary
Background.
Around the world, the proportion of people who are obese (people with an unhealthy amount of body fat) is increasing. In the US, for example, 1 adult in 7 was obese in the mid 1970s. That is, their body mass index (BMI)—their weight in kilograms divided by their height in meters squared—was more than 30. Nowadays, 1 US adult in 3 has a BMI this high and, by 2025, it is predicted that 1 in 2 will be obese. This obesity epidemic is being driven by lifestyle changes that encourage the over-consumption of energy-rich foods and discourage regular physical activity. The resultant energy imbalance leads to weight gain (the excess energy is stored as body fat or adipose tissue) and also triggers numerous metabolic changes, alterations in the chemical processes that convert food into the energy and various substances needed to support life. These obesity-related metabolic changes increase a person's risk of developing adverse health conditions such as diabetes, a condition in which dangerously high levels of sugar from food accumulate in the blood.
Why Was This Study Done?
The changes in human fat in obesity have not been completely understood, although the abnormal metabolism of adipose tissue is increasingly seen as playing a critical part in excessive weight gain. It has been very difficult to decipher which molecular and metabolic changes associated with obesity are the result of becoming obese, and which might contribute towards the acquisition of obesity in humans in the first place. To discover more about the influence of environment on obesity-induced metabolic changes, the researchers in this study have investigated these changes in pairs of genetically identical twins.
What Did the Researchers Do and Find?
The researchers recruited 14 pairs of genetically identical Finnish twins born between 1975 and 1979 who were “obesity discordant”—that is, one twin of each pair had a BMI of about 25 (not obese); the other had a BMI of about 30 (obese). The researchers took fat and blood samples from each twin, determined the insulin sensitivity of each, and measured the body composition and various fat stores of each. They found that the obese twins had more subcutaneous, intra-abdominal, and liver fat and were less insulin sensitive than the non-obese twins. Insulin sensitivity correlated with the amount of liver fat. Analysis of gene expression in the fat samples showed that 19 gene pathways (mainly inflammatory pathways) were expressed more strongly (up-regulated) in the obese twins than the non-obese twins, whereas seven pathways were down-regulated. The most highly down-regulated pathway was a mitochondrial pathway involved in amino acid breakdown, but mitochondrial energy metabolism pathways were also down-regulated. Finally, mitochondrial DNA copy number in fat was reduced in the obese twins by nearly half, a novel observation that could partly account for the obesity-induced metabolic defects of these individuals.
What Do These Findings Mean?
These and other findings identify several pathways that are involved in the development of obesity and insulin resistance. In particular, they suggest that changes in mitochondrial energy production pathways and in mitochondrial amino acid metabolism pathways could play important roles in the development of obesity and of insulin resistance and in the accumulation of liver fat even in young obese people. The study design involving identical twins has here produced some evidence for aberrations in molecules critical for acquired obesity. The results suggest that careful management of obesity by lifestyle changes has the potential to correct the obesity-related metabolic changes in fat that would otherwise lead to diabetes and other adverse health conditions in obese individuals. In addition, they suggest that the development of therapies designed to correct mitochondrial metabolism might help to reduce the illnesses associated with obesity.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050051.
The MedlinePlus encyclopedia has pages on obesity and diabetes (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on all aspects of obesity (in English and Spanish)
The UK National Health Service's health Web site (NHS Direct) provides information about obesity
The International Obesity Taskforce provides information about preventing obesity and on diabetes and obesity
The UK Foods Standards Agency and the United States Department of Agriculture provide online tools and useful advice about healthy eating for adults and children
Information is available for patients and carers from the US National Diabetes Information Clearinghouse on diabetes, including information on insulin resistance
doi:10.1371/journal.pmed.0050051
PMCID: PMC2265758  PMID: 18336063
14.  "The metabolic syndrome... is dead": These reports are an exaggeration 
The debates continue over the validity of the metabolic syndrome concept. The continuous increment of the obesity pandemic is almost worldwide paralleled by rising rates of metabolic syndrome prevalence. Then, it seems obvious that these debates drove the need for further investigations as well as a deeper cooperation between relevant national and international organizations regarding the issue. Instead, part of the scientific community elected to totally "dismiss" the concept of the metabolic syndrome. Meanwhile, the best available evidence from three consecutive large meta-analyses has systematically shown that people with metabolic syndrome are at increased risk of cardiovascular events. The most recent and largest of them included near one million patients (total n = 951,083). The investigators concluded that the metabolic syndrome is associated with a 2-fold increase in cardiovascular outcomes and a 1.5-fold increase in all-cause mortality rates. One of the ways to hit the metabolic syndrome is an utterly simplistic view on this concept as a predictive tool only. Of course, the presence of the metabolic syndrome possesses a definite predictive value, but first of all it is a widely accepted concept regarding a biological condition based on the complex and interrelated pathophysiological mechanisms starting from excess central adiposity and insulin resistance. Therefore, it is completely unfair to compare it with statistically constructed predictive tools, including stronger prognostic variables even unrelated to each other from the biological point of view. For example, in the criteria for metabolic syndrome (in contrast to Framingham score) age and cholesterol - presumably low density lipoprotein - cholesterol (LDL-C) - levels are not included, as well as a variety of strong predictors used in other risk-stratification scores: previous myocardial infarction, heart failure, smoking, family history, etc. However, the metabolic syndrome identifies additional important residual vascular risk mainly associated with insulin resistance and atherogenic dyslipidemia (low high density lipoprotein-cholesterol (HDL-C), high triglycerides, small, dense LDL-C). Therefore, the metabolic syndrome could be a useful additional contributor in estimation of global cardiovascular risk beyond age, high LDL-C or other standard risk factors. The components of the metabolic syndrome have partially overlapping mechanisms of pathogenic actions mediated through common metabolic pathways. Therefore their total combined effect could be less than the summed of the individual effects. The concept that the metabolic syndrome is a consequence of obesity and insulin resistance, provides a useful "life-style changes" approach for prevention and treatment: caloric restriction, weight-loss and increased physical activity. The next step could theoretically be pharmacological interventions such as metformin, acarbose, fibrates, weight-loss drugs (currently only orlistat is practically available) and perhaps glucagon-like peptide-1 agonists. A third step should probably be kept for bariatric surgery.
doi:10.1186/1475-2840-10-11
PMCID: PMC3036609  PMID: 21269524
15.  Androgen effects on skeletal muscle: implications for the development and management of frailty 
Asian Journal of Andrology  2014;16(2):203-212.
Androgens have potent anabolic effects on skeletal muscle and decline with age in parallel to losses in muscle mass and strength. This loss of muscle mass and function, known as sarcopenia, is the central event in development of frailty, the vulnerable health status that presages adverse outcomes and rapid functional decline in older adults. The potential role of falling androgen levels in the development of frailty and their utility as function promoting therapies in older men has therefore attracted considerable attention. This review summarizes current concepts and definitions in muscle ageing, sarcopenia and frailty, and evaluates recent developments in the study of androgens and frailty. Current evidence from observational and interventional studies strongly supports an effect of androgens on muscle mass in ageing men, but effects on muscle strength and particularly physical function have been less clear. Androgen treatment has been generally well–tolerated in studies of older men, but concerns remain over higher dose treatments and use in populations with high cardiovascular risk. The first trials of selective androgen receptor modulators (SARMs) suggest similar effects on muscle mass and function to traditional androgen therapies in older adults. Important future directions include the use of these agents in combination with exercise training to promote functional ability across different populations of older adults, as well as more focus on the relationships between concurrent changes in hormone levels, body composition and physical function in observational studies.
doi:10.4103/1008-682X.122581
PMCID: PMC3955329  PMID: 24457838
ageing; androgens; body composition; frailty; muscle; physical function; sarcopenia; selective androgen receptor modulators; sex hormones; testosterone
16.  Sarcopenic Obesity: Prevalence and Association With Metabolic Syndrome in the Korean Longitudinal Study on Health and Aging (KLoSHA) 
Diabetes Care  2010;33(7):1652-1654.
OBJECTIVE
We investigated the prevalence of sarcopenic obesity (SO) and its relationship with metabolic syndrome in a community-based elderly cohort in Korea.
RESEARCH DESIGN AND METHODS
In this study, 287 men and 278 women aged 65 or older were recruited. Sarcopenia was defined as the appendicular skeletal muscle mass (ASM) divided by height squared (Ht2) (kg/m2) or by weight (Wt) (%) of <1 SD below the sex-specific mean for young adults. Obesity was defined as a visceral fat area ≥100 cm2.
RESULTS
The prevalence of SO was 16.7% in men and 5.7% in women with sarcopenia defined by ASM/Ht2; however, it was 35.1% in men and 48.1% in women by ASM/Wt. Using ASM/Wt, the homeostasis model assessment of insulin resistance of subjects with SO was higher and they were at higher risk for metabolic syndrome (odds ratio [OR] 8.28 [95% CI 4.45–15.40]) than the obese (5.51 [2.81–10.80]) or sarcopenic group (2.64 [1.08–6.44]).
CONCLUSIONS
SO defined by ASM/Wt was more closely associated with metabolic syndrome than either sarcopenia or obesity alone.
doi:10.2337/dc10-0107
PMCID: PMC2890376  PMID: 20460442
17.  Obesity and Physical Frailty in Older Adults: A Scoping Review of Intervention Trials 
Many frail older adults are thin, weak, and undernourished; this component of frailty remains a critical concern in the geriatric field. However, there is also strong evidence that excessive adiposity contributes to frailty by reducing the ability of older adults to perform physical activities and increasing metabolic instability. Our scoping review explores the impact of being obese on physical frailty in older adults by summarizing the state of the science for both clinical markers of physical function and biomarkers for potential underlying causes of obesity-related decline. We used the five-stage methodological framework of Arksey and O’Malley to conduct a scoping review of randomized trials of weight loss and/or exercise interventions for obesity (BMI ≥ 30 kg/m2) in older adults (aged > 60 yrs), examining the outcomes of inflammation, oxidative stress, and lipid accumulation in muscle, as well as direct measures of physical function. Our initial search yielded 212 articles; exclusion of cross-sectional and observational studies, cell culture and animal studies, disease-specific interventions, and articles published before 2001 led to a final result of 21 articles. Findings of these trials included the following major points: The literature consistently confirmed benefits of lifestyle interventions to physical function assessed at the clinical level. Generally speaking, weight loss alone produced a greater effect than exercise alone and the best outcomes were achieved with a combination of weight loss and exercise, especially exercise programs that combined aerobic, resistance, and flexibility training. Weight loss interventions tended to reduce markers of inflammation and/or oxidative damage when more robust weight reduction was achieved and maintained over time, whereas exercise did not change markers of inflammation. However, participation in a chronic exercise program did reduce the oxidative stress induced by an acute bout of exercise. Weight loss interventions consistently reduced lipid accumulation in the muscle; however, in response to exercise, three studies showed an increase and two a decrease in muscle lipid infiltration. In summary, this scoping review identified strong clinical evidence that weight reduction and/or exercise interventions can improve physical function and biomarkers of physical dysfunction among overweight/obese older adults, supporting the suggestion that excessive adiposity contributes to physical frailty. However, the evidence also suggests a complexity of metabolic influences, both systemically and within muscle, which has not been elucidated to date. Considerable further study is needed to examine the mechanisms by which lifestyle interventions influence physical frailty before the net impact of such interventions can be fully understood.
doi:10.1016/j.jamda.2013.11.008
PMCID: PMC4023554  PMID: 24445063
Obesity; frailty; older adults; physical function; inflammation; oxidative stress; muscle lipid infiltration
18.  The effect of 12 weeks of aerobic, resistance or combination exercise training on cardiovascular risk factors in the overweight and obese in a randomized trial 
BMC Public Health  2012;12:704.
Background
Evidence suggests that exercise training improves CVD risk factors. However, it is unclear whether health benefits are limited to aerobic training or if other exercise modalities such as resistance training or a combination are as effective or more effective in the overweight and obese. The aim of this study is to investigate whether 12 weeks of moderate-intensity aerobic, resistance, or combined exercise training would induce and sustain improvements in cardiovascular risk profile, weight and fat loss in overweight and obese adults compared to no exercise.
Methods
Twelve-week randomized parallel design examining the effects of different exercise regimes on fasting measures of lipids, glucose and insulin and changes in body weight, fat mass and dietary intake. Participants were randomized to either: Group 1 (Control, n = 16); Group 2 (Aerobic, n = 15); Group 3 (Resistance, n = 16); Group 4 (Combination, n = 17). Data was analysed using General Linear Model to assess the effects of the groups after adjusting for baseline values. Within-group data was analyzed with the paired t-test and between-group effects using post hoc comparisons.
Results
Significant improvements in body weight (−1.6%, p = 0.044) for the Combination group compared to Control and Resistance groups and total body fat compared to Control (−4.4%, p = 0.003) and Resistance (−3%, p = 0.041). Significant improvements in body fat percentage (−2.6%, p = 0.008), abdominal fat percentage (−2.8%, p = 0.034) and cardio-respiratory fitness (13.3%, p = 0.006) were seen in the Combination group compared to Control. Levels of ApoB48 were 32% lower in the Resistance group compared to Control (p = 0.04).
Conclusion
A 12-week training program comprising of resistance or combination exercise, at moderate-intensity for 30 min, five days/week resulted in improvements in the cardiovascular risk profile in overweight and obese participants compared to no exercise. From our observations, combination exercise gave greater benefits for weight loss, fat loss and cardio-respiratory fitness than aerobic and resistance training modalities. Therefore, combination exercise training should be recommended for overweight and obese adults in National Physical Activity Guidelines.
This clinical trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), registration number: ACTRN12609000684224.
doi:10.1186/1471-2458-12-704
PMCID: PMC3487794  PMID: 23006411
Obesity; Overweight; Cardiovascular risk factors; Exercise training
19.  Functional Impairment is Associated with Low Bone and Muscle Mass among Persons Aging with HIV-Infection 
Background
Disability and frailty are associated with osteoporosis, obesity, and sarcopenia. HIV-infected persons have early functional impairment, but the association between body composition and functional impairment is unknown.
Methods
HIV-1-infected participants on combination antiretroviral therapy with virologic suppression, aged 45–65 years, had standardized physical function measures. In a nested analysis, 30 low- and 48 high-functioning cases and controls were matched by age, gender, and time since HIV diagnosis. Bone mineral density, fat mass, and lean body mass (LBM) were assessed by dual-energy X-ray absorptiometry. Odds ratios (OR) with 95% confidence intervals were obtained from conditional logistic regression.
Results
Mean age was 53 years, mean CD4+ lymphocytes 598 cells/μL, and 96% had plasma HIV-1 RNA <50 copies/mL. Low- and high-function subjects had similar CD4+lymphocyte count and duration and type of antiretroviral therapy. Lower T-scores at the hip (OR 3.8 [1.1, 12.5]) and lumbar spine (OR 2.3 [1.1, 4.5]) and lower LBM (OR 1.1 [1.0, 1.2]) were associated with significantly greater odds of low function (p≤0.03). Lower insulin-like growth hormone (IGF-1: OR 5.0 [1.4, 20.0]) and IGF-1 binding protein 3 (OR 3.3 [1.7, 9.9]) increased the odds of low functional status (p≤0.02). Fat mass and lower 25-OH vitamin D did not increase the odds of low functional status (p>0.05).
Conclusions
Functional impairment in HIV-1-infected persons on successful antiretroviral therapy is associated with low muscle mass, low bone mineral density and low IGF-1 and IGFBP-3. These characteristics may be a manifestation of early “somatopause” in middle-aged HIV-infected adults.
doi:10.1097/QAI.0b013e318289bb7e
PMCID: PMC3654048  PMID: 23392468
20.  From muscle wasting to sarcopenia and myopenia: update 2012 
Human muscle undergoes constant changes. After about age 50, muscle mass decreases at an annual rate of 1–2 %. Muscle strength declines by 1.5 % between ages 50 and 60 and by 3 % thereafter. The reasons for these changes include denervation of motor units and a net conversion of fast type II muscle fibers into slow type I fibers with resulting loss in muscle power necessary for activities of daily living. In addition, lipids are deposited in the muscle, but these changes do not usually lead to a loss in body weight. Once muscle mass in elderly subjects falls below 2 standard deviations of the mean of a young control cohort and the gait speed falls below 0.8 m/s, a clinical diagnosis of sarcopenia can be reached. Assessment of muscle strength using tests such as the short physical performance battery test, the timed get-up-and-go test, or the stair climb power test may also be helpful in establishing the diagnosis. Serum markers may be useful when sarcopenia presence is suspected and may prompt further investigations. Indeed, sarcopenia is one of the four main reasons for loss of muscle mass. On average, it is estimated that 5–13 % of elderly people aged 60–70 years are affected by sarcopenia. The numbers increase to 11–50 % for those aged 80 or above. Sarcopenia may lead to frailty, but not all patients with sarcopenia are frail—sarcopenia is about twice as common as frailty. Several studies have shown that the risk of falls is significantly elevated in subjects with reduced muscle strength. Treatment of sarcopenia remains challenging, but promising results have been obtained using progressive resistance training, testosterone, estrogens, growth hormone, vitamin D, and angiotensin-converting enzyme inhibitors. Interesting nutritional interventions include high-caloric nutritional supplements and essential amino acids that support muscle fiber synthesis.
doi:10.1007/s13539-012-0089-z
PMCID: PMC3505577  PMID: 23160774
Sarcopenia; Muscle mass; Prevalence; Morbidity
21.  Metabolic Syndrome, Sarcopenia and Role of Sex and Age: Cross-Sectional Analysis of Kashiwa Cohort Study 
PLoS ONE  2014;9(11):e112718.
Recent epidemiological evidence suggests that effects of cardiovascular risk factors may vary depending on sex and age. In this study, we assessed the associations of metabolic syndrome (MetS) with sarcopenia and its components in older adults, and examined whether the associations vary by sex and age. We also tested if any one of the MetS components could explain the associations. We conducted a cross-sectional analysis of the baseline data from the cohort study conducted in Kashiwa city, Chiba, Japan in 2012 which included 1971 functionally-independent, community-dwelling Japanese adults aged 65 years or older (977 men, 994 women). Sarcopenia was defined based on appendicular skeletal muscle mass, grip strength and usual gait speed. MetS was defined based on the National Cholesterol Education Program’s Adult Treatment Panel-III criteria. The prevalence of sarcopenia was 14.2% in men and 22.1% in women, while the prevalence of MetS was 43.6% in men and 28.9% in women. After adjustment for potential confounders, MetS was positively associated with sarcopenia in men aged 65 to 74 years (odds ratio 5.5; 95% confidence interval 1.9–15.9) but not in older men or women. Among the sarcopenia components, MetS was associated with lower muscle mass and grip strength, particularly in men aged 65 to 74 years. The associations of MetS with sarcopenia and its components were mainly driven by abdominal obesity regardless of sex or age. In conclusion, MetS is positively associated with sarcopenia in older men. The association is modified by sex and age, but abdominal obesity is the main contributor to the association across sex and age.
doi:10.1371/journal.pone.0112718
PMCID: PMC4236117  PMID: 25405866
22.  The anabolic catabolic transforming agent (ACTA) espindolol increases muscle mass and decreases fat mass in old rats 
Background
Sarcopenia, the age-related, progressive loss of skeletal muscle mass, strength, and function, is a considerable socioeconomic burden by increasing risks of falls, fractures, and frailty. Moreover, sarcopenic patients are often obese and therapeutic options are very limited.
Methods
Here, we assessed the efficacy of espindolol on muscle mass in 19-month-old male Wistar Han rats (weight, 555 ± 18 g), including safety issues. Rats were randomized to treatment with 3 mg/kg/day espindolol (n = 8) or placebo (n = 14) for 31 days.
Results
Placebo-treated rats progressively lost body weight (−15.5 ± 7.2 g), lean mass (−1.5 ± 4.2 g), and fat mass (−15.6 ± 2.7 g), while espindolol treatment increased body weight (+8.0 ± 6.1 g, p < 0.05), particularly lean mass (+43.4 ± 3.5 g, p < 0.001), and reduced fat mass further (−38.6 ± 3.4 g, p < 0.001). Anabolic/catabolic signaling was assessed in gastrocnemius muscle. Espindolol decreased proteasome and caspase-3 proteolytic activities by approximately 50 % (all p < 0.05). Western blotting showed a reduced expression of key catabolic regulators, including NFκB, MuRF1, and LC-3 (all p < 0.01). The 50- and 26-kDa forms of myostatin were downregulated fivefold and 20-fold, respectively (both p < 0.001). Moreover, 4E-BP-1 was reduced fivefold (p < 0.01), while phospho-PI3K was upregulated fivefold (p < 0.001), although Akt expression and phosphorylation were lower compared to placebo (all p < 0.05). No regulation of p38 and expression of ERK1/2 were observed, while phosphorylation of p38 was reduced (−54 %, p < 0.001) and ERK1/2 was increased (115 and 83 %, respectively, both p < 0.01). Espindolol did not affect cardiac function (echocardiography) or clinical plasma parameters.
Conclusion
Espindolol reversed the effects of aging/sarcopenia, particularly loss of muscle mass and increased fat mass. Thus, espindolol is an attractive candidate drug for the treatment of sarcopenia patients.
Electronic supplementary material
The online version of this article (doi:10.1007/s13539-013-0125-7) contains supplementary material.
doi:10.1007/s13539-013-0125-7
PMCID: PMC4053568  PMID: 24272787
Sarcopenia; Anabolic catabolic transforming agent (ACTA); Espindolol; Muscle mass; Fat mass
23.  Sarcopenia: European consensus on definition and diagnosis 
Age and Ageing  2010;39(4):412-423.
The European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. EWGSOP included representatives from four participant organisations, i.e. the European Geriatric Medicine Society, the European Society for Clinical Nutrition and Metabolism, the International Association of Gerontology and Geriatrics—European Region and the International Association of Nutrition and Aging. These organisations endorsed the findings in the final document.
The group met and addressed the following questions, using the medical literature to build evidence-based answers: (i) What is sarcopenia? (ii) What parameters define sarcopenia? (iii) What variables reflect these parameters, and what measurement tools and cut-off points can be used? (iv) How does sarcopenia relate to cachexia, frailty and sarcopenic obesity?
For the diagnosis of sarcopenia, EWGSOP recommends using the presence of both low muscle mass + low muscle function (strength or performance). EWGSOP variously applies these characteristics to further define conceptual stages as ‘presarcopenia’, ‘sarcopenia’ and ‘severe sarcopenia’. EWGSOP reviewed a wide range of tools that can be used to measure the specific variables of muscle mass, muscle strength and physical performance. Our paper summarises currently available data defining sarcopenia cut-off points by age and gender; suggests an algorithm for sarcopenia case finding in older individuals based on measurements of gait speed, grip strength and muscle mass; and presents a list of suggested primary and secondary outcome domains for research.
Once an operational definition of sarcopenia is adopted and included in the mainstream of comprehensive geriatric assessment, the next steps are to define the natural course of sarcopenia and to develop and define effective treatment.
doi:10.1093/ageing/afq034
PMCID: PMC2886201  PMID: 20392703
sarcopenia; elderly; muscle strength; muscle mass; physical performance
24.  An overview of sarcopenia: facts and numbers on prevalence and clinical impact 
Human muscle undergoes constant changes. After about age 50, muscle mass decreases at an annual rate of 1–2%. Muscle strength declines by 1.5% between ages 50 and 60 and by 3% thereafter. The reasons for these changes include denervation of motor units and a net conversion of fast type II muscle fibers into slow type I fibers with resulting loss in muscle power necessary for activities of daily living. In addition, lipids are deposited in the muscle, but these changes do not usually lead to a loss in body weight. Once muscle mass in elderly subjects falls below 2 standard deviations of the mean of a young control cohort and the gait speed falls below 0.8 m/s, a clinical diagnosis of sarcopenia can be reached. Assessment of muscle strength using tests such as the short physical performance battery test, the timed get-up-and-go test, or the stair climb power test may also be helpful in establishing the diagnosis. Sarcopenia is one of the four main reasons for loss of muscle mass. On average, it is estimated that 5–13% of elderly people aged 60–70 years are affected by sarcopenia. The numbers increase to 11–50% for those aged 80 or above. Sarcopenia may lead to frailty, but not all patients with sarcopenia are frail—sarcopenia is about twice as common as frailty. Several studies have shown that the risk of falls is significantly elevated in subjects with reduced muscle strength. Treatment of sarcopenia remains challenging, but promising results have been obtained using progressive resistance training, testosterone, estrogens, growth hormone, vitamin D, and angiotensin-converting enzyme inhibitors. Interesting nutritional interventions include high-caloric nutritional supplements and essential amino acids that support muscle fiber synthesis.
doi:10.1007/s13539-010-0014-2
PMCID: PMC3060646  PMID: 21475695
Sarcopenia; Muscle mass; Prevalence; Morbidity
25.  An overview of sarcopenia: facts and numbers on prevalence and clinical impact 
Human muscle undergoes constant changes. After about age 50, muscle mass decreases at an annual rate of 1–2%. Muscle strength declines by 1.5% between ages 50 and 60 and by 3% thereafter. The reasons for these changes include denervation of motor units and a net conversion of fast type II muscle fibers into slow type I fibers with resulting loss in muscle power necessary for activities of daily living. In addition, lipids are deposited in the muscle, but these changes do not usually lead to a loss in body weight. Once muscle mass in elderly subjects falls below 2 standard deviations of the mean of a young control cohort and the gait speed falls below 0.8 m/s, a clinical diagnosis of sarcopenia can be reached. Assessment of muscle strength using tests such as the short physical performance battery test, the timed get-up-and-go test, or the stair climb power test may also be helpful in establishing the diagnosis. Sarcopenia is one of the four main reasons for loss of muscle mass. On average, it is estimated that 5–13% of elderly people aged 60–70 years are affected by sarcopenia. The numbers increase to 11–50% for those aged 80 or above. Sarcopenia may lead to frailty, but not all patients with sarcopenia are frail—sarcopenia is about twice as common as frailty. Several studies have shown that the risk of falls is significantly elevated in subjects with reduced muscle strength. Treatment of sarcopenia remains challenging, but promising results have been obtained using progressive resistance training, testosterone, estrogens, growth hormone, vitamin D, and angiotensin-converting enzyme inhibitors. Interesting nutritional interventions include high-caloric nutritional supplements and essential amino acids that support muscle fiber synthesis.
doi:10.1007/s13539-010-0014-2
PMCID: PMC3060646  PMID: 21475695
Sarcopenia; Muscle mass; Prevalence; Morbidity

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