Re: "Epidemiology of insulin-like growth factor-I in elderly men and women. The Rancho Bernardo Study".
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Aged↗
Biomedical subjects
R Roubenoff
Publications and source records attributed to R Roubenoff.
Monocyte cytokine production in an elderly population: effect of age and inflammation.
OBJECTIVE: To determine the association among aging, inflammation, and cytokine production by peripheral blood mononuclear cells. POPULATION AND METHODS: We examined production of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), IL-1 receptor antagonist (IL-1Ra), and IL-6 in 711 elderly participants in the Framingham Heart Study (mean age, 79 y) and 21 young healthy volunteers (mean age, 39 y). The elderly subjects were categorized by serum C-reactive protein (CRP) concentration, a marker of systemic inflammation. RESULTS: Production of IL-6 (p < .00001) and IL-1Ra (p < .00001) was higher in the elderly subjects than in the control group. IL-6 production increased with increasing CRP, whereas IL-1RA was uniformly elevated in elderly subjects regardless of CRP. However, we found no difference in the production of IL-1 beta or TNF-alpha between the young and elderly groups, regardless of CRP status. IL-6 population correlated with IL-1 beta (r = .36, p < .0001) and TNF-alpha production (r = .25, p < .0001), but IL-1Ra production did not. CONCLUSION: Production of IL-6 and IL-1Ra--but not IL-1 beta or TNF-alpha--was increased in the elderly compared to healthy, young subjects. The increase in IL-6 also correlated with increased production of CRP, a marker of inflammation. However, IL-1Ra was increased in the elderly independently of CRP production. Although limited by the small control group, these data suggest that dysregulation of some inflammatory cytokines occurs with age, but the role of inflammation in aging remains unclear.
Adult↗
Body fat and skeletal muscle mass in relation to physical disability in very old men and women of the Framingham Heart Study.
BACKGROUND: Low muscle mass has been assumed to be associated with disability, but no studies confirming this association have been published. High body weight and high body mass index, both rough indicators of body fatness, have been shown to increase the risk for disability; however, the specific role of body fatness has not been studied. METHODS: The relations of skeletal muscle mass and percent body fat with self-reported physical disability were studied in 753 men and women aged 72 to 95 years. Cross-sectional data from biennial examination 22 (1992-1993) of the Framingham Heart Study were used. Body composition was assessed by dual-energy x-ray absorptiometry. Disability was scored as any versus none on a 9-item questionnaire. RESULTS: Total body and lower extremity muscle mass were not associated with disability in either men or women. However, a strong positive association between percent body fat and disability was observed. The odds ratio for disability in those in the highest tertile of body fatness was 2.69 (95% confidence interval 1.45-5.00) for women and 3.08 (1.22-7.81) for men compared to those in the lowest tertile. The increased risk could not be explained by age, education, physical activity, smoking, alcohol use, estrogen use (women only), muscle mass, and health status. Analyses restricting disability to mobility items gave similar results. CONCLUSIONS: In contrast to current assumptions, low skeletal muscle mass was not associated with self-reported physical disability. Persons with a high percent body fat had high levels of disability. Because it cannot be ruled out that persons with low skeletal muscle mass dropped out earlier in the study, prospective studies are needed to further assess the relationship between body composition and physical disability.
Absorptiometry, Photon↗
The relationship between growth hormone kinetics and sarcopenia in postmenopausal women: the role of fat mass and leptin.
Sarcopenia, the decline in body cell mass (BCM) and especially in muscle mass with age, is an important age-related cause of frailty and loss of independence in the elderly. Because the decline in BCM with age parallels a decline in GH secretion from young adulthood to old age, loss of GH secretion has been considered an important contributory cause of sarcopenia in the elderly. To test this hypothesis in a group of healthy postmenopausal women (n = 15; mean +/- SD age, 66.9 +/- 7.8 yr), 24-h GH concentrations and secretory kinetics were correlated with BCM (measured by whole body counting of 40K) and percent body fat (measured by dual energy x-ray absorptiometry or neutron inelastic scattering). Serum leptin levels were determined as a measure of adipocyte mass. Contrary to prediction, GH secretion was lower in women with higher BCM (r = 0.50; P < 0.05), whereas their mean fat mass was higher (r = 0.51, P < 0.05). These data indicate that sarcopenia in postmenopausal women is not associated with reduced GH secretion and is inversely correlated with fat mass. Serum leptin levels were inversely associated with GH secretion (r = -0.67; P < 0.006). Although a causal relationship has not been demonstrated, these data suggest that leptin could modulate GH secretion through its action on the aging hypothalamic-pituitary axis, or that GH regulates leptin secretion.
Adipocytes↗
Cytokine production and nutritional status in hemodialysis patients.
Malnutrition is an important predictor of mortality in patients on chronic hemodialysis, however the pathogenesis of wasting in this population remains unclear. Experimental data suggest that the dialysis procedure per se leads to enhanced catabolism, as well as direct loss of plasma amino acids and proteins into the dialysate. In the present study, the primary hypothesis examined is that hemodialysis-induced cytokine production is associated with reductions in lean body mass and other plasma markers of nutrition. We used the production of interleukin-1 receptor antagonist (IL-1Ra) by peripheral blood mononuclear cells (PBMC) as an indicator of cytokine production. PBMC were obtained pre-dialysis on the first and second sessions of the week in a cohort of 16 patients on chronic hemodialysis using reprocessed cellulose dialyzers who fulfilled rigorous entry criteria designed to eliminate known etiologies of increased cytokine production, e.g. chronic infections. PBMCs were either immediately frozen (cell content) or incubated for 24 hours at 37 degrees C in the presence or absence of endotoxin 10 ng/ml and total IL-1Ra was measured by radioimmunoassay. Nutritional staus was assessed using body mass index (BMI), total body potassium (TBK), anthropometry-derived arm muscle area (AMA), and measurements of plasma albumin, transferrin, total cholesterol, and triglycerides. Over the subsequent 3 months, patients were monitored carefully for pyrogen reactions, hemodynamic stability and intra-interdialytic symptoms. There was a direct correlation of cell content of IL-1Ra with several indices of nutritional status including BMI (r = 0.90, p = 0.0001), AMA (r = 0. 77, p = 0.0008), serum total cholesterol (r = 0.57, p = 0.03) and serum triglycerides (r = 0. 73, p = 0.002). Endotoxin-stimulated IL-1Ra production correlated directly with AMA (r = 0.59, p = 0.02), TBK (r = 0.71, p = 0.01) and serum triglycerides (r = 0.51, p = 0.05). These studies suggest a direct correlation between nutrition and cytokine production, and that malnutrition could depress cytokine production and potentially contribute to reduced immune responsiveness in patients on chronic hemodialysis.
Adult↗
Exercise and the treatment of wasting: aging and human immunodeficiency virus infection.
A common feature of human immunodeficiency virus (HIV) infection and aging is the loss of skeletal muscle mass. Although the causes of this loss of muscle are multifactorial, there may be some shared characteristics to this loss, and therefore common strategies for its prevention or reversal. For example, loss of muscle mass early in life and early in the progression of HIV infection may result from decreased levels of physical activity. The rapid loss of skeletal muscle mass at the end of life (sometimes referred to as failure to thrive syndrome) and in acquired immunodeficiency syndrome (AIDS) patients may also have common cause: cachexia. However, it also must be pointed out that loss of skeletal muscle mass with advancing age also may result from losses of motor units, decreased rate of skeletal muscle protein synthesis, and impaired regulation of appetite. These factors have not been demonstrated to be consequences of HIV infection. The use of exercise to treat the losses of muscle size, strength, and functional capacity holds great promise. Although the losses of muscle with HIV infection may be more rapid and dramatic than those seen with aging, resistance exercise training can attenuate or arrest this loss. In elderly people, resistance exercise has been demonstrated to result in increased nitrogen balance, muscle mass and strength, functional capacity, energy requirements, and when combined with a protein calorie supplement, increased energy intake. The use of resistance exercise in HIV-infected patients may also provide similar results. This review discusses many of the changes in body composition, physiological function, and metabolism associated with aging and HIV infection. The specific effects of exercise in the elderly and in patients infected with HIV on the treatment of muscle wasting, and its consequences are also discussed.
Aging↗
The association of peripheral monocyte derived interleukin 1beta (IL-1beta), IL-1 receptor antagonist, and tumor necrosis factor-alpha with osteoarthritis in the elderly.
OBJECTIVE: To examine the association of peripheral blood mononuclear cell (PBMC) derived interleukin 1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), tumor necrosis factor alpha (TNF-alpha), and radiographic osteoarthritis (OA) in the elderly. METHODS: A total of 703 subjects (436 women, 267 men, mean age 78.5+/-4.5 yrs) had both knee and hand radiographs, and cytokines were measured during the 22nd biennial examination of the Framingham Cohort. PBMC derived IL-1beta , IL-1Ra, and TNF-alpha production was assessed using a non-cross reacting polyclonal radioimmunoassay. Knee OA was defined as a score of > 2 using a modified Kellgren and Lawrence scale. The presence of osteophytes and joint space narrowing were scored separately on a 0-3 scale, in which disease was defined a priori as a score > 0 for each feature. Sex-specific odds ratios were calculated for knee OA after adjusting for weight, history of knee injury, and use of estrogen and nonsteroidal antiinflammatory drugs. RESULT: No uniform associations were found for IL-1beta or IL-1Ra in men, or for TNF-alpha production and radiographic OA in either sex. We found possible associations for the highest levels of IL-1beta production and the presence of knee osteophytes [OR=2.0 (1.2-3.5)] and joint space narrowing [OR=1.7 (1.1-2.8)] in women. Our data suggested a possible protective effect for IL-1Ra production and hand OA in women [OR=0.6 (0.4-1.0)]. CONCLUSION: We found no consistent association of PBMC cytokine production and radiographic OA. However, women with the highest production of IL-1beta and IL-1Ra had respectively higher rates of knee OA and lower rates of hand OA than expected.
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Feeding tubes in prevention of pneumonia.
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Deglutition Disorders↗
Adjuvant arthritis as a model of inflammatory cachexia.
OBJECTIVE: To determine whether adjuvant arthritis (AA) leads to changes in body composition and cytokine production similar to those seen in patients with rheumatoid arthritis. METHODS: AA was induced in Lewis rats using Freund's complete adjuvant. Body cell mass was measured by determining the concentration of total exchangeable potassium using 42K gavage. Splenocyte production of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) was measured by bioassay. Weight and food intake were also measured. RESULTS: Animals that developed AA lost 6% of their body weight by the onset of clinically evident arthritis (day 14; P < 0.01) and lost 20% by the end of the inflammatory phase of AA (day 28; P < 0.0001). Body cell mass fell 24.7 +/- 8.6% (mean +/- SEM) in animals with AA, but did not change significantly in controls (increase of 6.3 +/- 7.9%) (P < 0.03). Pair-fed animals lost one-fourth of the weight lost by the animals with AA (P < 0.01), indicating that anorexia alone does not explain inflammatory cachexia. Weight loss was correlated with TNF alpha production by spleen mononuclear cells (r = 0.68, P < 0.007), and a weaker correlation was seen with IL-1 production (r = 0.45, P < 0.04). CONCLUSION: AA in rats is a useful model of inflammatory cachexia that mimics the human pathophysiology in important ways, and is consistent with cytokine-driven cachexia in chronic inflammatory arthritis.
Animals↗
Abnormal homocysteine metabolism in rheumatoid arthritis.
OBJECTIVE: To assess total homocysteine (tHcy) metabolism in patients with rheumatoid arthritis (RA). METHODS: Assessments were performed to determine the fasting levels of tHcy and the increase in tHcy in response to methionine (Met) challenge in blood samples from 28 patients with RA and 20 healthy age-matched control subjects. RESULTS: Fasting levels of tHcy were 33% higher in the RA patients than in the control subjects (mean +/- SD 11.7 +/- 1.5 nmoles/ml versus 8.8 +/- 1.1 nmoles/ml; P < 0.01). Four hours after Met challenge, the increase in plasma tHcy levels (delta tHcy) was higher in the RA patients (20.9 +/- 10.4 nmoles/ml) than in the control subjects (15.5 +/- 1.6 nmoles/ml) (P < 0.02). In a subgroup analysis, the delta tHcy in patients taking methotrexate (12.9 +/- 2.2 nmoles/ml) did not differ from that in the control group, while the delta tHcy in patients not taking methotrexate (25.3 +/- 1.7 nmoles/ml) was significantly higher (P < 0.0001). CONCLUSION: Elevated tHcy levels occur commonly in patients with RA, and may explain some of the increased cardiovascular mortality seen in such patients. Studies of the prevalence and mechanism of hyperhomocysteinemia in RA are warranted.
Adult↗
Standardization of nomenclature of body composition in weight loss.
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Body Composition↗
Total body potassium and body fat: relevance to aging.
Understanding the mechanisms that govern sarcopenia (depletion of muscle mass with age) may suggest ways to preserve lean tissue and functional capacity, and to maintain quality of life in the elderly. We investigated the body-composition changes in normal aging in a cross-sectional study of 188 healthy volunteers aged 20-89 y, which examines the differences in body cell mass and fat as a function of age. In aging, the assumptions of indirect body-composition-measurement techniques, such as the "constant" hydration coefficient of lean body mass or the "constant" density of fat-free mass, may not hold. Therefore, we selected body-composition-measurement techniques that are not sensitive to assumptions about the composition of lean tissue. Cellular mass, lean body mass, and fat were assessed "directly" by total body potassium (TBK) measurements and neutron inelastic scattering. Our results show that TBK content declines at a rate of 7.20 +/- 1.00 mg K.kg body wt-1.y-1 for females (r = 0.601, P < or = 0.001) and 9.16 +/- 0.96 mg K.kg body wt-1.y-1 for males (r = 0.710, P < or = 0.001). Body fat measurements by neutron inelastic scattering have shown a significant increase of percentage body fat with age for female volunteers between the ages of 20 and 50 y and a continuous increase for male volunteers throughout adult life.
Adult↗
Application of bioelectrical impedance analysis to elderly populations.
BACKGROUND: Bioelectrical impedance analysis (BIA) can potentially be used to estimate body composition in large populations studied at multiple sites. However, it is not clear whether age-specific BIA equations are necessary for accurate application of BIA to research on elderly subjects. METHODS: We compared a published equation designed to predict fat-free mass (FFM) that had been derived in a young healthy population (mean age 27 y; mean BMI 23.9 kg/m2), with equations that we developed for the elderly by using data from 455 participants in the Framingham Heart Study (78 Y; 27.3 kg/m2), using dual-energy x-ray absorptiometry (DXA) as a reference technique. The BIA equations were then compared in an independent sample of 283 participants in the New Mexico Aging Process Study (76 y, 25.5 kg/m2), who also underwent BIA and DXA. RESULTS: When the young-population equation was applied to Framingham, it caused an overestimation of FFM in heavier subjects that was eliminated by use of the age-specific equation. However, when the two equations were tested in the New Mexico population, the published equation gave estimates of FFM that were closer to DXA than the Framingham equations did. CONCLUSIONS: The accuracy of a BIA equation depends on the body composition of the population of the population and the validation method rather than on age per se. Application of BIA to elderly populations requires uniform validation procedures in the actual study population, rather than reliance on age-specific equations.
Absorptiometry, Photon↗
Inflammatory and hormonal mediators of cachexia.
Body composition is a reflection of the metabolic state of the organism. However, because the time course of change in body composition is slower than that of metabolic processes, measurement of body composition offers a unique way of assessing the organism's physiologic status. The hormonal and immune mediators that control metabolism, and thus body composition, can be divided into three categories: day-to-day regulators (insulin and glucagon), life cycle-related hormones (estrogens and androgens, growth hormone, prolactin, thyroid hormones, catecholamines, corticosteroids) and immunologic mediators (the cytokines interleukin-1, tumor necrosis factor, and interleukin-6). Although the cytokines can clearly drive metabolism and thus body composition in various illnesses, it is not yet clear whether they also play a homeostatic role in the age-related changes in body composition that we now call sarcopenia.
Aging↗
Association of insulin-like growth factor-I with body composition, weight history, and past health behaviors in the very old: the Framingham Heart Study.
OBJECTIVES: We examined correlates of insulin-like growth factor-I (IGF-I), an indicator of growth hormone levels, to identify factors associated with higher levels of IGF-I in old age. DESIGN: Nested study of cross-sectional correlates and early-life predictors of IGF-I level. SETTING: A longitudinal cohort study, the Framingham Heart Study. PARTICIPANTS: A total of 790 men and women (mean age 78.5, range 72-94), who had weight, waist and hip circumferences measured at the time of IGF-I measurement. MEASUREMENTS: Association of IGF-I with weight, fat distribution, functional status, nutritional indicators, and past health behaviors was assessed. We also examined IGF-I in relation to body composition derived from dual energy X-ray absorptiometry. RESULTS: IGF-I levels declined with age in both men and women. However, low IGF-I did not show expected associations with low lean mass and increased body fat. Current functional status and grip strength were not associated with IGF-I Low IGF-I was associated with weight loss in men; the strongest associations were with indicators of poorer nutritional status in both men and women. Levels of IGF-I in old age did not vary by past health behaviors. CONCLUSION: Although IGF-I declined with age, these data from the Framingham Heart Study did not show expected cross-sectional associations of weight, body fat, and lean mass. The strongest associations were between IGF-I and nutritional indicators. These results suggest caution may be warranted with regard to use of IGF-I as an indicator of growth hormone.
Aged↗
Failure to thrive, sacropenia and functional decline in the elderly.
At this time, there are no commonly accepted definitions for either the "failure to thrive" syndrome or for the newly described syndrome of sarcopenia. This lack of a common definition makes it difficult to contrast study results and understand the etiology of these syndromes. This article reviews the current state of understanding of these conditions and suggests potential mechanisms that may be further investigated.
Aged↗
Plasma homocysteine as a risk factor for atherothrombotic events in systemic lupus erythematosus.
BACKGROUND: The aim of this study was to assess whether plasma homocysteine is a risk factor for stroke and other thrombotic events in patients with systemic lupus erythematosus (SLE)--a condition known to be associated with premature atherothrombotic complications. METHODS: In this prospective study, we investigated the association between homocysteine and risk of stroke and thrombotic events in 337 SLE patients in the Hopkins Lupus Cohort Study, with follow-up of 1619 person-years (mean 4.8 [SD 1.7] years). Each patient had four follow-up assessments per year to obtain information about established risk factors for thrombosis and coronary artery disease. The prospectively defined endpoints were occurrence of stroke and arterial or venous thrombotic events between 1987 and 1995. Blood samples were taken at study entry from fasting patients. Plasma homocysteine, folate, vitamin B12, and pyridoxal 5'-phosphate (PLP) concentrations were measured. Raised homocysteine concentrations were defined as more than 14.1 mumol/L. FINDINGS: 93% of the study population were women, 54% African American, and 45% white. The mean age of participants was 34.9 (SD 11.7) years. During follow-up there were 29 cases of stroke and 31 arterial thrombotic events. Raised homocysteine concentrations were found in 51 (15%) SLE patients. The log-transformed total homocysteine concentrations correlated with serum folate (r = 0.31, p = 0.0001). In univariate analyses, raised homocysteine concentrations were significantly associated with stroke (odds ratio 2.24 [95% CI 1.22-4.13], p = 0.01) and arterial thrombotic events (3.74 [1.96-7.13], p = 0.0001). After adjustment for established risk factors, total plasma homocysteine concentrations remained an independent risk factor for stroke (2.44 [1.04-5.75], p = 0.04) and arterial thromboses (3.49 [0.97-12.54], p = 0.05). INTERPRETATION: Homocysteine is a potentially modifiable, independent risk factor for stroke and thrombotic events in patients with SLE.
Adult↗
Body composition, metabolism, and resistance exercise in patients with rheumatoid arthritis.
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Adult↗