Muscle mass decreases with age, leading to "sarcopenia," or low relative muscle mass, in elderly people. Sarcopenia is believed to be associated with metabolic, physiologic, and functional impairments and disability. Methods of estimating the prevalence of sarcopenia and its associated risks in elderly populations are lacking. Data from a population-based survey of 883 elderly Hispanic and non-Hispanic white men and women living in New Mexico (the New Mexico Elder Health Survey, 1993-1995) were analyzed to develop a method for estimating the prevalence of sarcopenia. An anthropometric equation for predicting appendicular skeletal muscle mass was developed from a random subsample (n = 199) of participants and was extended to the total sample. Sarcopenia was defined as appendicular skeletal muscle mass (kg)/height2 (m2) being less than two standard deviations below the mean of a young reference group. Prevalences increased from 13-24% in persons under 70 years of age to >50% in persons over 80 years of age, and were slightly greater in Hispanics than in non-Hispanic whites. Sarcopenia was significantly associated with self-reported physical disability in both men and women, independent of ethnicity, age, morbidity, obesity, income, and health behaviors. This study provides some of the first estimates of the extent of the public health problem posed by sarcopenia.

Epidemiology of Sarcopenia among the Elderly in New Mexico

Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as "myokines." Recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. However, the first identified and most studied myokine is the gp130 receptor cytokine interleukin-6 (IL-6). IL-6 was discovered as a myokine because of the observation that it increases up to 100-fold in the circulation during physical exercise. Identification of IL-6 production by skeletal muscle during physical activity generated renewed interest in the metabolic role of IL-6 because it created a paradox. On one hand, IL-6 is markedly produced and released in the postexercise period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin action. This review focuses on the myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease.

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Muscle as an endocrine organ: focus on muscle-derived interleukin-6.

Background. A decline in muscle mass and muscle strength characterizes normal aging. As clinical and animal studies show it relationship between higher cytokine levels and low muscle mass, the aim of this study was to investigate whether markers, of inflammation are associated with muscle mass and strength in well-functioning elderly persons. Methods. We Used baseline data (1997-1998) of the Health, Aging, and Body Composition (Health ABC) Study on 3075 black and white men and women aged 70-79 years. Midthigh muscle cross-sectional area (computed tomography), appendicular muscle mass (dual-energy x-ray ab absorptiometry). isokinetic knee extensor strength (KinCom). and isometric inip strength were measured. plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assessed by enzyme-linked immunosorbent assay (ELISA). Results. Higher cytokine levels were generally associated with lower muscle mass and lower muscle strength. The most consistent relationship across the gender and race groups was observed for IL-6 and grip strength: per SD increase in IL-6, grip strength was 1.1 to 2.4 kg lower (p 1.80 pg/ml) as well as high levels of TNF-alpha (> 3.20 pg/ml) had a smaller muscle area, less appendicular mass. a lower knee extensor strength. and a lower grip strength compared to those with low levels of both cytokines. Conclusions. Higher plasma concentrations of IL-6 and TNF-alpha are associated with lower muscle mass and lower muscle strength in well-functioning older men and women. Higher cytokine levels. as often observed in healthy older persons. may contribute to the loss Of muscle mass and strength that accompanies aging.

Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study.

https://www.amjmed.com/article/S0002-9343(05)01054-5/pdf

Inflammatory markers and loss of muscle mass (sarcopenia) and strength.

Background. Sarcopenia refers to the loss of skeletal muscle mass with age. The objective of this study was to determine the prevalence of sarcopenia in a population of older, community-dwelling research volunteers. Methods. Appendicular skeletal muscle mass was measured by dual x-ray absorptiometry in 195 women aged 64 to 93 years and 142 men aged 64 to 92 years. We defined sarcopenia as appendicular skeletal muscle mass/height 2 (square meters) less than 2 standard deviations below the mean for young, healthy reference populations. We used two different reference populations and compared prevalence in our population to that reported in previous studies. Body mass index (BMI) was calculated and physical activity and performance were measured with the Physical Activity Scale for the Elderly, the Short Physical Performance Battery, and the Physical Performance Test. We measured health-related quality of life by using the SF-36 general health survey. Serum estrone, estradiol, sex hormone-binding globulin, parathyroid hormone, and 25-hydroxy vitamin D were measured in all participants and bioavailable testosterone was measured only in men. Leg press strength and leg press power were determined in men. Results. The prevalence of sarcopenia in our cohort was 22.6% in women and 26.8% in men. A subgroup analysis of women and men 80 years or older revealed prevalence rates of 31.0% and 52.9%, respectively. In women, skeletal muscle mass correlated significantly with BMI and levels of serum estrone, estradiol, and 25-hydroxy vitamin D; in men, it correlated significantly with BMI, single leg stance time, leg press strength, leg press power, SF-36 general health score, Physical Performance Test total score, and bioavailable testosterone levels. With the use of linear regression analysis, BMI was the only predictor of appendicular skeletal muscle mass in women, accounting for 47.9% of the variance (p < .05). In men, BMI accounted for 50.1%, mean strength accounted for 10.3%, mean power accounted for 4.1%, and bioavailable testosterone accounted for 2.6% of the variance in appendicular skeletal muscle mass (p <.05). Conclusions. Sarcopenia is common in adults over the age of 65 years and increases with age. BMI is a strong predictor of skeletal muscle mass in women and men. Strength, power, and bioavailable testosterone are further contributors in men. These data suggest that interventions to target nutrition, strength training, and testosterone replacement therapy should be further investigated for their role in preventing muscle loss with age.

Prevalence of Sarcopenia and Predictors of Skeletal Muscle Mass in Healthy, Older Men and Women

The cytokines IL-1 beta and TNF-alpha cause cachexia and hypermetabolism in animal models, but their role in human inflammation remains controversial. The relationship between in vitro cytokine production and metabolism was examined in 23 adults with RA and 23 healthy control subjects matched on age, sex, race, and weight. Body composition was measured by multicompartmental analysis of body cell mass, water, fat, and bone mass. Resting energy expenditure (REE) was measured by indirect calorimetry. Cytokine production by PBMC was measured by radioimmunoassay. Usual energy intake, physical activity, disability scores, medication use, and other confounders were also measured. Body cell mass was 13% lower (P < 0.00001), REE was 12% higher (P < 0.008), and physical activity was much lower (P < 0.001) in subjects with RA. Production of TNF-alpha was higher in RA than controls, both before and after stimulation with endotoxin (P < 0.05), while production of IL-1 beta was higher with endotoxin stimulation (P < 0.01). In multivariate analysis, cytokine production was directly associated with REE (P < 0.001) in patients but not in controls. While energy and protein intake were similar in the two groups and exceeded the Recommended Dietary Allowances, energy intake in subjects with RA was inversely associated with IL-1 beta production (P < 0.005). In this study we conclude that: loss of body cell mass is common in RA; cytokine production in RA is associated with altered energy metabolism and intake, despite a theoretically adequate diet; and TNF-alpha and IL-1 beta modulate energy metabolism and body composition in RA.

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Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation.

Certain body fat distribution patterns have been associated with increased risk for chronic disease since 1956, when Vauge proposed that specific obesity patterns could determine predisposition to diabetes, atherosclerosis and other disease1. Several investigators have confirmed that the “male-type” fat distribution pattern, characterized by increased abdominal adipose tissue, is associated with increased risk of cardiovascular disease and elevated plasma lipid and lipoprotein concentrations, independently of total body fat2,3. A mechanism has been suggested which relates the “male-type” obesity pattern to certain metabolic alterations. Specifically, lipolysis in the intra-abdominal adipose tissue could expose the liver to a high flux of free fatty acids, due to its anatomic proximity to the hepatic portal vein. As a result, the hepatic insulin and lipid metabolism is significantly altered3. New methods for measuring distribution of adipose tissue were generated for investigating this hypothesis. Indirect techniques, such as the waist-to-hip ratio, have produced results consistent with this theory. The relative importance of genetic factors as well as the role of peripheral fat remain unknown.

Measurement of Regional Body Fat in Vivo in Humans by Simultaneous Detection of Regional Carbon and Oxygen, Using Neutron Inelastic Scattering at Low Radiation Exposure

Sarcopenia, defined as theloss ofskeletal muscle with age, may lead to frailty, fractures due to falls, and reduced immunity to disease.Byunderstanding the causes ofmuscle loss with age we will be able to develop ways ofmaintaining functional capacity and qualityoflile for the elderly. ElementalPartitionAnalysis (EPA) is a new approach to body composition assessment A major element of thebody is measured and then, by means ofother measurements, is partitioned to the contributing body compartments. We developed a model for measuring total body muscle by applying the EPA method to total body phosphorus (TBP). We measure TBP (headexcluded) by in vivo fast neutron activation analysis using the reaction 31P(n,a)M The main contributors to TB? are bone and skeletal muscle. Adipose tissue and the liver contribute less than 3%. We use dual-energy X-ray absorptiometry (1)XA) to evaluatethe coniribution ofbone to TBP. Corrections are applied for the small contributions ofthe liver and adipose tissue to TBP to derive

Hong Zhuang

Papers

Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation.

Measurement of Regional Body Fat in Vivo in Humans by Simultaneous Detection of Regional Carbon and Oxygen, Using Neutron Inelastic Scattering at Low Radiation Exposure

Use of fast neutrons for assessing sarcopenia by measuring body phosphorus: relevance to health and quality of life of the elderly