Search

While hypogammaglobulinemia is associated with COPD exacerbations, it is unknown whether frequent exacerbators have specific defects in antibody production/function. We hypothesized that reduced quantity/function of serum pneumococcal antibodies correlate with exacerbation risk in the SPIROMICS cohort. We measured total pneumococcal IgG in n = 764 previously vaccinated participants with COPD. In a propensity-matched subset of n = 200 with vaccination within five years (n = 50 without exacerbations in the previous year; n = 75 with one, n = 75 with ≥2), we measured pneumococcal IgG for 23 individual serotypes, and pneumococcal antibody function for 4 serotypes. Higher total pneumococcal IgG, serotype-specific IgG (17/23 serotypes), and antibody function (3/4 serotypes) were independently associated with fewer prior exacerbations. Higher pneumococcal IgG (5/23 serotypes) predicted lower exacerbation risk in the following year. Pneumococcal antibodies are inversely associated with exacerbations, supporting the presence of immune defects in frequent exacerbators. With further study, pneumococcal antibodies may be useful biomarkers for immune dysfunction in COPD.

Background. Neopterin a GTP metabolite expressed by macrophages, is a marker of immune activation. We hypothesize that levels of this serum marker alter with donor age, reflecting increased chronic immune activation in normal aging. In addition to age. we assessed gender, race, body mass index (BMI), and percentage of body fat (% fat) as potential covariates. Methods. Serum was obtained from 426 heahhy participants whose age ranged from 18 to 87 years. Anthropometric measures included % fat and BMI. Neopterin concentrations were measured by competitive ELISA. The paired associations between neopterin and age. BMI, or % fat were analyzed by Spearman's correlation or by linear regression of log- transformed neopterin, whereas overall associations were modeled by multiple regression of log-transformed neopterin as a function of age. gender, race, BMI, % fat, and interaction terms. Results. Across all participants, neopterin exhibited a positive association with age, BMI, and % fat. Multiple regression modeling of neopterin in women and men as a function of age, BMI, and race revealed that each covariate contributed significantly to neopterin values and that optimal modeling required an interaction term between race and BMI. The covariate % fat was highly correlated with BMI and could be substituted for BMI to yield similar regression coefficients. Conclusion. The association of age and gender with neopterin levels and their modification by race, BMI. or % fat reflect the biology underlying chronic immune activation and perhaps gender differences in disease incidence, morbidity, and mortality. Key Words: Neopterin--Immune activation--Inflammation BMI--Homeostasis. doi: 10.1093/gerona/glq066

Over the last decade there has been an enormous expansion of research focused on defining the role of inflammation in aging, age-related diseases, disability, and frailty. The availability of methods to measure cytokines and other inflammatory mediators or markers with high sensitivity and specificity is critically important. Enzyme-linked immunosorbent assay (ELISA), the most widely used and best validated method, is limited by its ability to measure only a single protein in each sample. Recent developments in serum cytokine quantification technology include multiplex arrays, which offer the potential of better evaluating the complexity and dynamic nature of inflammatory responses and offer substantial cost and sample savings over traditional ELISA measurements. Despite potential advantages of this new technology, experience with these techniques is limited, and it has not emerged to date as the gold standard in inflammatory mediator measurement. This article reviews ELISA and the emerging multiplex technologies, compares the cost and effectiveness of recently developed multiplex arrays with traditional ELISA technology, and provides specific recommendations for investigators interested in measuring serum inflammatory mediators in older adults. Key Words: ELISA--Muhiplex arrays--Cytokines--Inflammation--Aging.

Background. It is hypothesized that free radical damage contributes to aging. Age-related decline in activity of the antioxidant enzyme glutathione peroxidase (GPx) may contribute to increased free radicals. We hypothesized that GPx activity decreases with age in a population of older women with disability. Methods. Whole blood GPx activity was measured in baseline stored samples from participants in the Women's Health and Aging Study I, a cohort of disabled community-dwelling older women. Linear regression was used to determine cross- sectional associations between GPx activity and age, adjusting for hemoglobin, coronary disease, diabetes, selenium, and body mass index. Results. Six hundred one participants had complete demographic, disease, and laboratory information. An inverse association was observed between GPx and age (regression coefficient = -2.9, p < .001), indicating that for each 1-year increase in age, GPx activity decreased by 2.9 [micro]mol/min/L. This finding remained significant after adjustment for hemoglobin, coronary disease, diabetes, and selenium, but not after adjustment for body mass index and weight loss. Conclusion, This is the first study to examine the association between age and GPx activity in an older adult cohort with disability and chronic disease. These findings suggest that, after age 65, GPx activity declines with age in older women with disability. This decline does not appear to be related to diseases that have been previously reported to alter GPx activity. Longitudinal examination of GPx activity and other antioxidant enzymes in diverse populations of older adults will provide additional insight into age- and disease-related changes in these systems. Key Words: Glutathione peroxidase--Oxidative stress--Aging--Older adult.

Background. The development of animal models that approximate human frailty is necessary to facilitate etiologic and treatment-focused frailty research. The genetically altered IL-[10.sup.tm/tm] mouse does not express the antiinflammatory cytokine interleukin 10 (IL-10) and is, like frail humans, more susceptible to inflammatory pathway activation. We hypothesized thai with increasing age, IL-[10.sup.tm/tm] mice would develop physical and biological characteristics similar to those of human frailty as compared to C57BL/6J control mice. Methods. Strength, activity, serum IL-6, and skeletal muscle gene expression were compared between age-matched and gender-matched [IL-10.sup.tm/tm] mice on C57BL/6J background and C57BL/6J control mice using a longitudinal design for physical characteristics and cross-sectional design for biological characteristics. Results. Strength levels declined significantly faster in [IL-10.sup.tm/tm] compared to control mice with increasing age. Serum IL-6 levels were significantly higher in older compared to younger IL-[10.sup.tm/tm] mice and were significantly higher in older IL-[10.sup.tm/tm] compared to age- and gender-matched C57BL/6J control mice. One hundred twenty-five genes, many related to mitochondrial biology and apoptosis, were differentially expressed in skeletal muscle between 50-week-old IL-[10.sup.tm/tm] and 50-week-old C57BL/6J mice. No expression diffrences between IL-[10.sup.tm/tm] age groups were identified by quantitative polymerase chain reaction. Conclusion. These physical and biological findings suggest that the IL-[10.sup.tm/tm] mouse develops inflammation and strength decline consistent with human frailty at an earlier age compared to C57BL/6J control type mice. This finding provides rationale for the further development and utilization of the IL-[10.sup.tm/tm] mouse to study the biological basis of frailty. Key Words: Frailty--Mouse model.

The novel osmolyte 2-sulfotrehalose in haloalkaliphilic archaea was analyzed to determine its role in the accumulation of organic solutes in species ofnatronococcus and natronobacterium. The study utilized a nuclear magnetic resonance spectroscopy to quantify and identify the organic compatible solutes in the bacteria. Results reveal that the concentration of the novel dissacharide increased with increasing amount of external NaCl. Sucrose, however was am effective means om controlling biosynthesis.