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1.  Cytomegalovirus is associated with reduced telomerase activity in the Whitehall II cohort 
Experimental gerontology  2013;48(4):385-390.
Telomere length and telomerase activity have received increased attention as markers of cellular aging, but the determinants of inter-individual variation in these markers are incompletely understood. Cytomegalovirus (CMV) infection may be particularly important for telomere and telomerase dynamics due to its dramatic impact on peripheral blood lymphocyte composition, i.e., increasing the number and proportions of highly differentiated T cells that are characterized by shorter telomere length (TL) and lowered telomerase activity (TA). However, the possible relationship between CMV infection and leukocyte TL and TA has not been well-examined in vivo. This study examined the associations of CMV seropositivity and CMV IgG antibodies with leukocyte (TL) and (TA) in a sample of 434 healthy individuals (ages 53–76) from the Whitehall II cohort. Positive CMV serostatus was significantly associated with lower TA among women, and higher CMV IgG antibody levels were associated with lower TA in the overall sample. However, neither CMV seropositivity nor CMV IgG antibody levels (reflecting subclinical reactivation) among the seropositive were significantly associated with TL. These associations were robust to adjustment for age, employment grade, BMI, and smoking status. The results demonstrate that CMV seropositivity and subclinical reactivation predict lower TA. Future longitudinal studies should test whether the association of CMV with lower TA contributes to accelerated telomere shortening over time.
PMCID: PMC3626117  PMID: 23403382
telomeres; telomerase; cytomegalovirus; infections; Whitehall II
2.  Elevated HbA1c levels and the accumulation of differentiated T cells in CMV+ individuals 
Diabetologia  2015;58(11):2596-2605.
Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27−CD45RA+/−; or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV+ and CMV− individuals.
A cross-sectional sample of participants from an occupational cohort study (n = 1,103, mean age 40 years, 88% male) were assessed for HbA1c and fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids), numbers of circulating effector memory (EM; CD27−CD45RA−) and CD45RA re-expressing effector memory (EMRA; CD27−CD45RA+) T cells, and CMV infection status. Self-report and physical examination assessed anthropometric, sociodemographic and lifestyle factors.
Among CMV+ individuals (n = 400), elevated HbA1c was associated with increased numbers of EM (B = 2.75, p < 0.01) and EMRA (B = 2.90, p < 0.01) T cells, which was robust to adjustment for age, sex, sociodemographic variables and lifestyle factors. Elevated EM T cells were also positively associated with total cholesterol (B = 0.04, p < 0.05) after applying similar adjustments. No associations were observed in CMV− individuals.
The present study identified consistent associations of unfavourable glucose and lipid profiles with accumulation of dCTLs in CMV+ individuals. These results provide evidence that the impact of metabolic risk factors on immunity and health can be co-determined by infectious factors, and provide a novel pathway linking metabolic risk factors with accelerated immunosenescence.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-015-3731-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
PMCID: PMC4589544  PMID: 26290049
Cholesterol; CMV; Cytomegalovirus; Diabetes; Glucose; Haemoglobin A1c; HbA1c; Immune ageing; Metabolic syndrome; T cell
3.  Neighborhood-level stressors, social support, and diurnal patterns of cortisol: the Chicago Community Adult Health Study 
Social science & medicine (1982)  2012;75(6):1038-1047.
Neighborhood disadvantage has consistently been linked to increased rates of morbidity and mortality, but the mechanisms through which neighborhood environments may get “under the skin” remain largely unknown. Differential exposure to chronic environmental stressors has been identified as a potential pathway linking neighborhood disadvantage and poor health, particularly through the dysregulation of stress-related biological pathways such as cortisol secretion, but the majority of existing observational studies on stress and neuroendocrine functioning have focused exclusively on individual-level stressors and psychosocial characteristics. This paper aims to fill that gap by examining the association between features of the neighborhood environment and the diurnal cortisol patterns of 308 individuals from Chicago, Illinois, USA. We found that respondents in neighborhoods with high levels of perceived and observed stressors or low levels of social support experienced a flatter rate of cortisol decline throughout the day. In addition, overall mean cortisol levels were found to be lower in higher stress, lower support neighborhoods. This study adds to the growing evidence of hypocortisolism among chronically stressed adult populations and suggests hypocortisolism rather than hypercortisolism as a potential mechanism linking social disadvantage to poor health.
PMCID: PMC3556931  PMID: 22698925
USA; cortisol; neighborhood effects; health inequalities; multi-level modeling; stress
4.  Persistent Viral Pathogens and Cognitive Impairment Across the Life Course in the Third National Health and Nutrition Examination Survey 
The Journal of Infectious Diseases  2013;209(6):837-844.
Background. Herpesviruses have been linked to cognitive impairment in older individuals but little is known about the association in the general US population.
Methods. We determined whether cytomegalovirus (CMV) and herpes simplex virus 1 (HSV-1) seropositivity were associated with cognitive impairment among children (aged 6–16 years) and adults aged 20–59 or ≥60 years, using data from the National Health and Nutrition Examination Survey (NHANES) III. Linear and logistic regression models were used to examine the associations between pathogen seropositivity and cognitive impairment.
Results. Among children, HSV-1 seropositivity was associated with lower reading and spatial reasoning test scores (β, −0.69; 95% confidence interval [CI], −1.18 to −.21 and β, −0.82; 95% CI, −1.29 to −.36, respectively). Among middle-aged adults, HSV-1 and CMV seropositivity were associated with impaired coding speed (odds ratio [OR], 1.54; 95% CI, 1.13–2.11, and OR, 1.41; 95% CI, 1.09–1.82, respectively). CMV seropositivity was also associated with impaired learning and recall (OR, 1.43; 95% CI, 1.14–1.80). Among older adults, HSV-1 seropositivity was associated with immediate memory impairment (OR, 3.26; 95% CI, 1.68–6.32).
Conclusions. Future studies examining the biological pathways by which herpesviruses influence cognitive impairment across the life course are warranted.
PMCID: PMC3935478  PMID: 24253286
Cognitive impairment; herpes simplex virus-1; cytomegalovirus; lifecourse; NHANES
5.  Family poverty is associated with cytomegalovirus antibody titers in U.S children 
Early life environmental and psychological influences are thought to play an important role in the development of the immune system. Antibody response to latent herpesviruses has been used as an indirect measure of cell-mediated immune function but has seldom been applied to younger age groups.
We used data from the 1999–2004 National Health and Nutrition Examination Survey (NHANES) to test for an association between family poverty and continuous antibody response to cytomegalovirus (CMV) in U.S. children aged 6–16 (N= 2,226) using OLS regression.
Poverty was significantly associated with increased antibody levels among seropositive individuals. The association between income and antibody levels exhibited a threshold effect, with additional income beyond the poverty line not associated with increased antibody titers.
Early life social factors such as family poverty could have detrimental impacts on the developing immune system, with potentially important consequences for later life health outcomes.
PMCID: PMC3677208  PMID: 21895372
CMV; poverty; socioeconomic status; health disparities; NHANES; immunity
6.  Education and levels of salivary cortisol over the day in U.S. adults 
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is hypothesized to be an important pathway linking socioeconomic position and chronic disease.
This paper tests the association between education and the diurnal rhythm of salivary cortisol.
Up to 8 measures of cortisol (mean of 5.38 per respondent) over two days were obtained from 311 respondents, aged 18–70, drawn from the 2001–2002 Chicago Community Adult Health Study. Multi-level models with linear splines were used to estimate waking level, rates of cortisol decline, and area-under-the-curve over the day, by categories of education.
Lower education (0–11 years) was associated with lower waking levels of cortisol, but not the rate of decline of cortisol, resulting in a higher area-under-the-curve for more educated respondents throughout the day.
This study found evidence of lower cortisol exposure among individuals with less education and thus does not support the hypothesis that less education is associated with chronic over-exposure to cortisol.
PMCID: PMC3486742  PMID: 20812036
7.  Deeper and wider: income and mortality in the USA over three decades 
Background Literature on the socio-economic ‘gradient’ in health often asserts that income is associated with better health not only for the very poor, but also across the entire income distribution. In addition, changes in the shape of the association between incomes during a period of increasing economic inequality have not been previously studied. The goal of the current study was to estimate and compare the shape of the relationship between income and mortality in the USA for the 1970s, the 1980s and the 1990s.
Methods Using income and mortality data from the Panel Study of Income Dynamics for respondents aged 35–64 years, we used a Bayesian Cox Model with regression splines to model the risk of mortality over three 10-year follow-up periods. To identify whether income was more strongly associated with mortality at different parts of the income distribution, we treated income as a linear spline with an unknown knot location.
Results The shape of the association between income and mortality was quite non-linear, with a much stronger association at lower levels of income. The relationship between income and mortality in the USA was also not invariant across time, with the increased risk of death associated with lower income applying to an increasing proportion of the US population over time (9th percentile of income in 1970–79, 20th percentile in 1980–89 and 32nd percentile in 1990–99).
Conclusions Our analyses do not support the claim that income is associated with mortality throughout the income distribution, nor is the association between income and mortality the same across periods. Based on our analyses, a focus on the bottom 30% of the income distribution would seem to return the greatest benefits in reducing socio-economic inequalities in health.
PMCID: PMC3043282  PMID: 20980249
Income; mortality
8.  Cytomegalovirus antibodies in dried blood spots: a minimally invasive method for assessing stress, immune function, and aging 
Cytomegalovirus (CMV) is a prevalent herpesvirus with links to both stress and aging. This paper describes and validates a minimally invasive method for assessing antibodies against CMV in finger stick whole blood spot samples for use as an indirect marker of an aspect of cell-mediated immunity.
Analysis of CMV in dried blood spot samples (DBS) was based on modifications of a commercially available protocol for quantifying CMV antibodies in serum or plasma. The method was evaluated through analysis of precision, reliability, linearity, and correlation between matched serum and DBS samples collected from 75 volunteers. Correlation between DBS and plasma values was linear and high (Pearson correlation R = .96), and precision, reliability, and linearity of the DBS assay were within acceptable ranges.
The validity of a DBS assay for CMV antibodies will enable its inclusion in population-based surveys and other studies collecting DBS samples in non-clinical settings, increasing scientific understanding of the interaction of social and biological stress and immune function.
PMCID: PMC3031243  PMID: 21232134
9.  Socio-economic status, cortisol and allostatic load: a review of the literature 
Background The notion that chronic stress contributes to health inequalities by socio-economic status (SES) through physiological wear and tear has received widespread attention. This article reviews the literature testing associations between SES and cortisol, an important biomarker of stress, as well as the summary index of allostatic load (AL).
Methods A search of all published literature on the PubMed and ISI Web of Knowledge literature search engines was conducted using broad search terms. The authors reviewed abstracts and selected articles that met the inclusion criteria. A total of 26 published studies were included in the review.
Results Overall, SES was not consistently related to cortisol. Although several studies found an association between lower SES and higher levels of cortisol, many found no association, with some finding the opposite relationship. Lower SES was more consistently related to a blunted pattern of diurnal cortisol secretion, but whether this corresponded to higher or lower overall cortisol exposure varied by study. Approaches to collecting and analysing cortisol varied widely, likely contributing to inconsistent results. Lower SES was more consistently related to higher levels of AL, but primarily via the cardiovascular and metabolic components of AL rather than the neuroendocrine markers.
Conclusions Current empirical evidence linking SES to cortisol and AL is weak. Future work should standardize approaches to measuring SES, chronic stress and cortisol to better understand these relationships.
PMCID: PMC2755130  PMID: 19720725
Socio-economic status; cortisol; allostatic load
10.  Socioeconomic and Race/Ethnic Patterns in Persistent Infection Burden Among U.S. Adults 
The pathophysiological mechanisms that underlie health disparities by socioeconomic status and race/ethnicity are poorly understood. Promising new research suggests that the burden of persistent infection may influence adult disease risk and mortality. This article examines how multiple persistent infections cluster within individuals and how this clustering varies by socioeconomic position and race/ethnicity in U.S. adults.
We analyze data from the National Health and Nutrition Examination Survey III (N = 19,275) for adults aged 17–90 years. The clustering of infections within individuals is studied using tetrachoric correlations. Multiple indicator multiple cause models are used to analyze the infection burden construct as measured by seropositivity to Helicobacter pylori, cytomegalovirus, herpes simplex virus-1, and hepatitis B, focusing on the burden's distribution by socioeconomic position and race/ethnicity. The results are corroborated using ordered logistic regression for a commonly used count index of individual infections.
Seroprevalence of individual persistent infections is positively correlated, suggesting common factors related to exposure or susceptibility. Education, income, and race/ethnicity are strong and significant independent predictors of infection burden in U.S. adults in all models.
The disproportionate burden of persistent infections among disadvantaged groups across all ages may be one biologic pathway by which low socioeconomic position is related to increased rates of morbidity and mortality in the United States.
PMCID: PMC2655034  PMID: 19196638
Socioeconomic; Race; Ethnic; United states; Adults; Infection; Biomarkers

Results 1-10 (10)