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author:("Epel, melissa")
1.  Indirect effect of financial strain on daily cortisol output through daily negative to positive affect index in the Coronary Artery Risk Development in Young Adults Study 
Psychoneuroendocrinology  2013;38(12):10.1016/j.psyneuen.2013.07.016.
Daily affect is important to health and has been linked to cortisol. The combination of high negative affect and low positive affect may have a bigger impact on increasing HPA axis activity than either positive or negative affect alone. Financial strain may both dampen positive affect as well as increase negative affect, and thus provides an excellent context for understanding the associations between daily affect and cortisol. Using random effects mixed modeling with maximum likelihood estimation, we examined the relationship between self reported financial strain and estimated mean daily cortisol level (latent cortisol variable), based on six salivary cortisol assessments throughout the day, and whether this relationship was mediated by greater daily negative to positive affect index measured concurrently in a sample of 781 Coronary Artery Risk Development in Young Adults (CARDIA) Study participants. The analysis revealed that while no total direct effect existed for financial strain on cortisol, there was a significant indirect effect of high negative affect to low positive affect, linking financial strain to elevated cortisol. In this sample, the effects of financial strain on cortisol through either positive affect or negative affect alone were not significant. A combined affect index may be a more sensitive and powerful measure than either negative or positive affect alone, tapping the burden of chronic financial strain, and its effects on biology.
doi:10.1016/j.psyneuen.2013.07.016
PMCID: PMC3844074  PMID: 23969421
financial strain; cortisol; positive affect; negative affect
2.  Soda and Cell Aging: Associations between Sugar-Sweetened Beverage Consumption and Leukocyte Telomere Length in Healthy Adults from the National Health and Nutrition Examination Surveys 
American journal of public health  2014;104(12):2425-2431.
Objectives
We tested whether leukocyte telomere length maintenance, which underlies healthy cellular aging, provides a link between sugar-sweetened beverage (SSB) consumption and risk of cardiometabolic disease. We examined cross-sectional associations between consumption of SSBs, diet soda and fruit juice and telomere length in a nationally representative sample of healthy adults.
Methods
The study population included 5,309 adults, aged 20 to 65 years, with no prior history of diabetes or cardiovascular disease, from the 1999–2002 National Health and Nutrition Examination Surveys. Leukocyte telomere length was assayed from DNA specimens. Diet was assessed using 24-hour dietary recalls. Associations were examined using multivariate linear regression for the outcome of log-transformed telomere length.
Results
After adjustment for sociodemographic and health-related characteristics, sugar-sweetened soda consumption was associated with shorter telomeres (β=−0.010, 95% CI −0.020, −0.001, P=0.04). Consumption of 100% fruit juice was marginally associated with longer telomeres (β= 0.016, 95% CI −0.000, 0.033). No significant associations were observed between consumption of diet sodas or non-carbonated sugar-sweetened beverages and telomere length.
Conclusions
Regular consumption of sugar-sweetened sodas may influence metabolic disease development through accelerated cell aging.
doi:10.2105/AJPH.2014.302151
PMCID: PMC4229419  PMID: 25322305
3.  Childhood Socioeconomic Status, Telomere Length, and Susceptibility to Upper Respiratory Infection 
Low socioeconomic status (SES) during childhood and adolescence has been found to predict greater susceptibility to common cold viruses in adults. Here, we test whether low childhood SES is associated with shorter leukocyte telomere length in adulthood, and whether telomere length mediates the association between childhood SES and susceptibility to acute upper respiratory disease in adulthood.
At baseline, 196 healthy volunteers reported whether they currently owned their home and, for each year of their childhood, whether their parents owned the family home. Volunteers also had blood drawn for assessment of specific antibody to the challenge virus, and for CD8+CD28− T-lymphocyte telomere length (in a subset, n = 135). They were subsequently quarantined in a hotel, exposed to a virus (rhinovirus [RV] 39) that causes a common cold and followed for infection and illness (clinical cold) over 5 post-exposure days.
Lower childhood SES as measured by fewer years of parental home ownership was associated with shorter adult CD8+CD28− telomere length and with an increased probability of developing infection and clinical illness when exposed to a common cold virus in adulthood. These associations were independent of adult SES, age, sex, race, body mass, neuroticism, and childhood family characteristics. Associations with infections and colds were also independent of pre-challenge viral-specific antibody and season. Further analyses do not support mediating roles for smoking, alcohol consumption or physical activity but suggest that CD8+CD28− cell telomere length may act as a partial mediator of the associations between childhood SES and infection and childhood SES and colds.
doi:10.1016/j.bbi.2013.06.009
PMCID: PMC3795973  PMID: 23845919
4.  Longer leukocyte telomere length in Costa Rica's Nicoyan Peninsula: A population-based study 
Experimental gerontology  2013;48(11):10.1016/j.exger.2013.08.005.
Studies in humans suggest that leukocyte telomere length may act as a marker of biological aging. We investigated whether individuals in the Nicoya region of Costa Rica, known for exceptional longevity, had longer telomere length than those in other parts of the country. After controlling for age, age squared, rurality, rainy season and gender, mean leukocyte telomere length in Nicoya was substantially longer (81 base pairs, p<0.05) than in other areas of Costa Rica, providing evidence of a biological pathway to which this notable longevity may be related. This relationship remains unchanged (79 base pairs, p<0.05) after statistically controlling for nineteen potential biological, dietary and social and demographic mediators. Thus the difference in mean leukocyte telomere length that characterizes this unique region does not appear to be explainable by traditional behavioral and biological risk factors. More detailed examination of mean leukocyte telomere length by age shows that the regional telomere length difference declines at older ages.
doi:10.1016/j.exger.2013.08.005
PMCID: PMC3819141  PMID: 23988653
telomere length; Costa Rica; aging; biomarkers; socioeconomic; longevity
5.  Clues to Maintaining Calorie Restriction? Psychosocial Profiles of Successful Long-term Restrictors 
Appetite  2014;79:106-112.
To combat the obesity epidemic, interventions and treatment often recommend low-calorie dieting. Calorie restriction (CR) as a weight intervention, however, is often unsuccessful, as most people cannot sustain the behavior. Yet one small group has maintained extreme CR over years—members of the CR Society and followers of The CR Way. This study examined stable psychosocial characteristics of these individuals to identify traits that may promote success at long-term CR. In 65 participants, we measured diet, eating behaviors, and personality traits comparing calorie restrictors to two age-, gender-, ethnicity-, and education-matched comparison groups (normal weight and overweight/obese). We first tested whether the CR group restricted calories without indications of eating disorder pathology, and second, what crystallized psychosocial characteristics set them apart from their non-restricting comparisons. Results indicated the CR group averaged 10 years of CR but scored lower than comparison groups on measures of disordered eating (p < .001) and psychopathology (p < .001). Particularly against overweight/obese participants, CR participants scored lower on neuroticism (p < .04) and hostility (p < .01), and were stronger in future time orientation (p< .05). Overall, CR profiles reflected high self-control and well being, except for having few close relationships. This study suggests a potential predisposition for successful long-term CR without disordered eating. Since modifying trait factors may be unrealistic, there may be psychosocial boundaries to the capacity for sustaining CR. Paralleling a movement towards personalized medicine, this study points toward a personalized behavioral medicine model in behavioral nutrition and treatment of overweight/obesity.
doi:10.1016/j.appet.2014.04.006
PMCID: PMC4198019  PMID: 24747211
dieting; calorie restriction; obesity; personality; time perspective; eating disorders
6.  Good Stress, Bad Stress and Oxidative Stress: Insights from Anticipatory Cortisol Reactivity 
Psychoneuroendocrinology  2013;38(9):1698-1708.
Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F2α (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-OxoG) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as “peak” cortisol reactivity, while the increase from 0 to 15 min was defined as “anticipatory” cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (p<.01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-OxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants (p≤.01.) Intriguingly, among those with low chronic stress exposure, moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage. Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through frequent and sustained activation of the Hypothalamic-Pituitary-Adrenal axis. It also supports the less studied model of ‘eustress’ - that manageable levels of life stress may enhance psychobiological resilience to oxidative damage.
doi:10.1016/j.psyneuen.2013.02.004
PMCID: PMC4028159  PMID: 23490070
Oxidative stress; biological aging; chronic stress; acute stress; DNA/RNA damage; cortisol; hypothalamic-pituitary-adrenal axis; eustress; resilience; reactive oxygen species
7.  Stress and Telomere Biology: A Lifespan Perspective 
Psychoneuroendocrinology  2013;38(9):1835-1842.
In the past decade, the growing field of telomere science has opened exciting new avenues for understanding the cellular and molecular substrates of stress and stress-related aging processes ver the lifespan. Shorter telomere length is associated with advancing chronological age and also increased disease morbidity and mortality. Emerging studies suggest that stress accelerates the erosion of telomeres from very early in life and possibly even influences the initial (newborn) setting of telomere length. In this review, we highlight recent empirical evidence linking stress and mental illnesses at various times across the lifespan with telomere erosion. We first present findings in the developmental programming of telomere biology linking prenatal stress to newborn and adult telomere length. We then present findings linking exposure to childhood trauma and to certain mental disorders with telomere shortening. Last, we review studies that characterize the relationship between related health-risk behaviors with telomere shortening over the lifespan, and how this process may further buffer the negative effects of stress on telomeres. A better understanding of the mechanisms that govern and regulate telomere biology throughout the lifespan may inform our understanding of etiology and the long-term consequences of stress and mental illnesses on aging processes in diverse populations and settings.
doi:10.1016/j.psyneuen.2013.03.010
PMCID: PMC3735679  PMID: 23639252
Telomere length; telomerase; stress; lifespan; prenatal; fetal/developmental programming; childhood stress; mental health; depression; lifestyle
8.  Gender differences in the prospective associations of self-reported sleep quality with biomarkers of systemic inflammation and coagulation: findings from the Heart and Soul Study 
Journal of psychiatric research  2013;47(9):10.1016/j.jpsychires.2013.05.004.
Systemic inflammation is proposed as a putative mechanism underlying the link between poor sleep and cardiovascular disease. The aim of present study was to investigate the cross-sectional and prospective associations of self-reported sleep quality with biomarkers of inflammation and coagulation implicated in coronary heart disease (CHD) and to explore whether these associations differed between men and women. To this end, measures of sleep quality and markers of inflammation, including circulating levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (CRP), and fibrinogen were assessed at baseline in 980 participants with established CHD and 626 at 5-year follow-up. In the sample as a whole, subjective sleep quality was unrelated to inflammatory markers in cross-sectional and prospective analyses. However, in gender stratified analyses, adjusting for age, ethnicity, education, body mass index, and regular snoring, poorer subjective sleep quality at baseline was prospectively associated with 5-year increases in IL-6 (b= 0.14, SE= 0.05, p= 0.003), CRP (b= 0.21, SE= 0.09, p= 0.02), and fibrinogen (b= 18.02, SE= 7.62, p= 0.02) in women but not men. These associations remained independent of lifestyle/psychosocial factors, medical comorbidities, medication use, and cardiac function. Women who reported baseline sleep disturbances characterized by a tendency to wake up too early in the morning also showed significant 5-year increases in circulating IL-6 that withstood covariate adjustment. Further research is necessary to elucidate the pathways that underlie gender-specific associations between subjective sleep quality and markers of inflammation and coagulation as this may help clarify gender disparities in CHD.
doi:10.1016/j.jpsychires.2013.05.004
PMCID: PMC3864775  PMID: 23746737
sleep; inflammation; gender; coronary heart disease
9.  Seasonal variation of peripheral blood leukocyte telomere length in Costa Rica: a population based observational study 
Objectives
Peripheral blood leukocyte telomere length is increasingly being used as a biomarker of aging, but its natural variation in human populations is not well understood. Several other biomarkers show seasonal variation, as do several determinants of leukocyte telomere length. We examined whether there was monthly variation in leukocyte telomere length in Costa Rica, a country with strong seasonal differences in precipitation and infection.
Methods
We examined a longitudinal population based cohort of 581 Costa Rican adults age 60 and above, from which blood samples were drawn between October 2006 and July 2008. Leukocyte telomere length was assayed from these samples using the quantitative PCR method. Multivariate regression models were used to examine correlations between month of blood draw and leukocyte telomere length.
Results
Telomere length from peripheral blood leukocytes varied by as much as 200 base pairs depending on month of blood draw, and this difference is not likely to be due to random variation. A moderate proportion of this association is statistically accounted for by month and region specific average rainfall. We found shorter telomere length associated with greater rainfall.
Conclusions
There are two possible explanations of our findings. First, there could be relatively rapid month-to-month changes in leukocyte telomere length. This conclusion would have implications for understanding the natural population dynamics of telomere length. Second, there could be seasonal differences in constituent cell populations. This conclusion would suggest that future studies of leukocyte telomere length use methods to account for the potential impact of constituent cell type.
doi:10.1002/ajhb.22529
PMCID: PMC4136920  PMID: 24615938
telomere length; seasonality; lymphocytes; infection; rainfall
10.  Chronic Stress Increases Vulnerability to Diet-Related Abdominal Fat, Oxidative Stress, and Metabolic Risk 
Psychoneuroendocrinology  2014;46:14-22.
Summary
Background
In preclinical studies, the combination of chronic stress and a high sugar/fat diet is a more potent driver of visceral adiposity than diet alone, a process mediated by peripheral Neuropeptide Y (NPY).
Methods
In a human model of chronic stress, we investigated whether the synergistic combination of highly palatable foods (HPF; high sugar/fat) and stress was associated with elevated metabolic risk. Using a case-control design, we compared 33 post-menopausal caregivers (the chronic stress group) to 28 age-matched low-stress control women on reported HPF consumption (modified Block Food Frequency Questionnaire), waistline circumference, truncal fat ultrasound, and insulin sensitivity using a three-hour oral glucose tolerance test. A fasting blood draw was assayed for plasma NPY and oxidative stress markers (8-hydroxyguanosine and F2-Isoprostanes).
Results
Among chronically stressed women only, greater HPF consumption was associated with greater abdominal adiposity, oxidative stress, and insulin resistance at baseline (all p’s ≤.01). Furthermore, plasma NPY was significantly elevated in chronically stressed women (p<.01), and the association of HPF with abdominal adiposity was stronger among women with high versus low NPY. There were no significant predictions of change over one-year, likely due to high stability (little change) in the primary outcomes over this period.
Discussion
Chronic stress is associated with enhanced vulnerability to diet-related metabolic risk (abdominal adiposity, insulin resistance, and oxidative stress). Stress-induced peripheral NPY may play a mechanistic role.
doi:10.1016/j.psyneuen.2014.04.003
PMCID: PMC4104274  PMID: 24882154
Psychological stress; obesity; abdominal adiposity; metabolic syndrome; pre-diabetes
11.  The Reward-Based Eating Drive Scale: A Self-Report Index of Reward-Based Eating 
PLoS ONE  2014;9(6):e101350.
Why are some individuals more vulnerable to persistent weight gain and obesity than are others? Some obese individuals report factors that drive overeating, including lack of control, lack of satiation, and preoccupation with food, which may stem from reward-related neural circuitry. These are normative and common symptoms and not the sole focus of any existing measures. Many eating scales capture these common behaviors, but are confounded with aspects of dysregulated eating such as binge eating or emotional overeating. Across five studies, we developed items that capture this reward-based eating drive (RED). Study 1 developed the items in lean to obese individuals (n = 327) and examined changes in weight over eight years. In Study 2, the scale was further developed and expert raters evaluated the set of items. Study 3 tested psychometric properties of the final 9 items in 400 participants. Study 4 examined psychometric properties and race invariance (n = 80 women). Study 5 examined psychometric properties and age/gender invariance (n = 381). Results showed that RED scores correlated with BMI and predicted earlier onset of obesity, greater weight fluctuations, and greater overall weight gain over eight years. Expert ratings of RED scale items indicated that the items reflected characteristics of reward-based eating. The RED scale evidenced high internal consistency and invariance across demographic factors. The RED scale, designed to tap vulnerability to reward-based eating behavior, appears to be a useful brief tool for identifying those at higher risk of weight gain over time. Given the heterogeneity of obesity, unique brief profiling of the reward-based aspect of obesity using a self-report instrument such as the RED scale may be critical for customizing effective treatments in the general population.
doi:10.1371/journal.pone.0101350
PMCID: PMC4076308  PMID: 24979216
12.  Speaking under pressure: Low linguistic complexity is linked to high physiological and emotional stress reactivity 
Psychophysiology  2013;51(3):257-266.
What can a speech reveal about someone's state? We tested the idea that greater stress reactivity would relate to lower linguistic cognitive complexity while speaking. In Study 1, we tested whether heart rate and emotional stress reactivity to a stressful discussion would relate to lower linguistic complexity. In Studies 2 and 3 we tested whether a greater cortisol response to a standardized stressful task including a speech (Trier Social Stress Test) would be linked to speaking with less linguistic complexity during the task. We found evidence that measures of stress responsivity (emotional and physiological) and chronic stress are tied to variability in the cognitive complexity of speech. Taken together, these results provide evidence that our individual experiences of stress or ‘stress signatures’—how our body and mind react to stress both in the moment and over the longer term—are linked to how complexly we speak under stress.
doi:10.1111/psyp.12171
PMCID: PMC4059522  PMID: 24354732
cognitive complexity; cognition; stress reactivity; cortisol reactivity; language
13.  Is the Belief in Meritocracy Palliative for Members of Low Status Groups? Evidence for a Benefit for Self-Esteem and Physical Health via Perceived Control 
Consensually held ideologies may serve as the cultural “glue” that justifies hierarchical status differences in society (e.g. Augustinos, 1998). Yet to be effective these beliefs need to be embraced by low-status groups. Why would members of low-status groups endorse beliefs that justify their relative disadvantage? We propose that members of low-status groups in the United States may benefit from some system-justifying beliefs (such as the belief in meritocracy) to the extent that these beliefs emphasize the perception of control over future outcomes. In 2 studies, among women, lower-SES women, and women of color, we found a positive relationship between the belief in meritocracy and well-being (self-esteem and physical health) that was mediated by perceived control. Members of low-status groups may benefit from some system-justifying beliefs to the extent that these beliefs, like the belief in meritocracy, emphasize the perception of control over future outcomes.
doi:10.1002/ejsp.1959
PMCID: PMC3769703  PMID: 24039310
System Justification; Meritocracy; Self-Esteem; Socio-economic Status
14.  Food insecurity with past experience of restrained eating is a recipe for increased gestational weight gain 
Appetite  2013;65:178-184.
Food insecurity is linked to higher weight gain in pregnancy, as is dietary restraint. We hypothesized that pregnant women exposed to marginal food insecurity, and who reported dietary restraint before pregnancy, will paradoxically show the greatest weight gain. Weight outcomes were defined as total kilograms, observed-to-recommended weight gain ratio, and categorized as adequate, inadequate or excessive weight gain based on 2009 Institute of Medicine guidelines. A likelihood ratio test assessed the interaction between marginal food insecurity and dietary restraint and found significant. Adjusted multivariate regression and multinomial logistic models were used to estimate weight gain outcomes. In adjusted models stratified by dietary restraint, marginal insecurity and low restraint was significantly associated with lower weight gain and weight gain ratio compared to food secure and low restraint. Conversely, marginal insecurity and high restraint was significantly associated with higher weight gain and weight gain ratio compared to food secure and high restraint. Marginal insecurity with high restraint was significantly associated with excessive weight gain. Models were consistent when restricted to low-income women and full-term deliveries. In the presence of marginal food insecurity, women who struggle with weight and dieting issues may be at risk for excessive weight gain.
doi:10.1016/j.appet.2013.01.018
PMCID: PMC3800106  PMID: 23402720
food insecurity; dietary restraint; weight gain; dieting; disordered eating; pregnancy
15.  Socioeconomic status, health behavior, and leukocyte telomere length in the National Health and Nutrition Examination Survey, 1999–2002 
The purpose of this study was to examine the association between socioeconomic status (SES) and leukocyte telomere length (LTL) – a marker of cell aging that has been linked to stressful life circumstances – in a nationally representative, socioeconomically and ethnically diverse sample of US adults aged 20–84. Using data from the National Health and Nutrition Examination Survey (NHANES), 1999–2002, we found that respondents who completed less than a high school education had significantly shorter telomeres than those who graduated from college. Income was not associated with LTL. African-Americans had significantly longer telomeres than whites, but there were no significant racial/ethnic differences in the association between education and telomere length. Finally, we found that the association between education and LTL was partially mediated by smoking and body mass index but not by drinking or sedentary behavior.
doi:10.1016/j.socscimed.2013.02.023
PMCID: PMC3666871  PMID: 23540359
socioeconomic status; cell aging; telomere length; health behavior; United States
16.  Relation between Leukocyte Telomere Length and Incident Coronary Heart Disease Events (From the 1995 Canadian Nova Scotia Health Survey) 
The American journal of cardiology  2013;111(7):962-967.
Leukocyte telomere length has been proposed as a biomarker of cellular aging and atherosclerosis. We sought to determine whether leukocyte telomere length is independently associated with incident coronary heart disease (CHD) in the general population. Telomere length was measured using a polymerase chain reaction method for participants enrolled in the 1995 Nova Scotia Health Survey (n=1,917). The primary endpoint was first occurrence of fatal and non-fatal CHD events. During a mean follow-up of 8.7 years, 164 fatal or non-fatal CHD events occurred. Compared to participants in the longest tertile of telomere length, those in the middle and shortest tertiles had increased incidence of CHD events (6.2, 11.2 and 12.2 per 1000 person-years, respectively). After adjustment for demographics, traditional risk factors and inflammatory markers including hs-CRP, IL-6, and sICAM-1, those in the middle tertile had significantly elevated risk for incident CHD (hazard ratio [HR] 1.63, 95% CI 1.07–2.51, p=0.02) compared to the longest tertile, whereas the risk for those in the shortest tertile was non-significantly elevated (HR 1.25, 95% CI 0.82–1.90, p=0.30). In conclusion, these findings do not support a linear association between leukocyte telomere length and incident CHD risk in the general population.
doi:10.1016/j.amjcard.2012.12.017
PMCID: PMC3602395  PMID: 23375186
coronary heart disease; telomere; risk prediction
17.  Omega-3 Fatty Acids, Oxidative Stress, and Leukocyte Telomere Length: A Randomized Controlled Trial 
Shorter telomeres have been associated with poor health behaviors, age-related diseases, and early mortality. Telomere length is regulated by the enzyme telomerase, and is linked to exposure to proinflammatory cytokines and oxidative stress. In our recent randomized controlled trial, omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation lowered the concentration of serum proinflammatory cytokines. This study assessed whether n-3 PUFA supplementation also affected leukocyte telomere length, telomerase, and oxidative stress. In addition to testing for group differences, changes in the continuous n-6:n-3 PUFA ratio were assessed to account for individual differences in adherence, absorption, and metabolism. The double-blind 4-month trial included 106 healthy sedentary overweight middle-aged and older adults who received (1) 2.5 g/day n-3 PUFAs, (2) l.25 g/day n-3 PUFAs, or (3) placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Supplementation significantly lowered oxidative stress as measured by F2-isoprostanes (p=0.02). The estimated geometric mean log-F2-isoprostanes values were 15% lower in the two supplemented groups compared to placebo. Although group differences for telomerase and telomere length were nonsignificant, changes in the n-6:n-3 PUFA plasma ratios helped clarify the intervention’s impact: telomere length increased with decreasing n-6:n-3 ratios, p=0.02. The data suggest that lower n-6:n-3 PUFA ratios can impact cell aging. The triad of inflammation, oxidative stress, and immune cell aging represents important pre-disease mechanisms that may be ameliorated through nutritional interventions. This translational research broadens our understanding of the potential impact of the n-6:n-3 PUFA balance. ClinicalTrials.gov identifier: NCT00385723
doi:10.1016/j.bbi.2012.09.004
PMCID: PMC3545053  PMID: 23010452
omega-3; omega-6; telomeres; inflammation; cell aging; nutritional neuroscience; oxidative stress; F2-isoprostanes; fish oil
18.  Maternal psychosocial stress during pregnancy is associated with newborn leukocyte telomere length 
Objective
In adults, one of the major determinants of leukocyte telomere length (LTL), a predictor of age-related diseases and mortality, is cumulative psychosocial stress exposure. More recently we reported that exposure to maternal psychosocial stress during intrauterine life is associated with LTL in young adulthood. The objective of the present study was to determine how early in life this effect of stress on LTL is apparent by quantifying the association of maternal psychosocial stress during pregnancy with newborn telomere length.
Study Design
In a prospective study of N = 27 mother-newborn dyads maternal pregnancy-specific stress was assessed in early gestation and cord blood peripheral blood mononuclear cells were subsequently collected and analyzed for LTL measurement.
Results
After accounting for the effects of potential determinants of newborn LTL (gestational age at birth, weight, sex, and exposure to antepartum obstetric complications), there was a significant, independent, linear effect of pregnancy-specific stress on newborn LTL that accounted for 25% of the variance in adjusted LTL (β = −0.099; P = .04).
Conclusion
Our finding provides the first preliminary evidence in human beings that maternal psychological stress during pregnancy may exert a “programming” effect on the developing telomere biology system that is already apparent at birth, as reflected by the setting of newborn LTL.
doi:10.1016/j.ajog.2012.11.033
PMCID: PMC3612534  PMID: 23200710
fetal/developmental programming of health and disease risk; maternal psychosocial stress; newborn telomere biology
19.  Educational Attainment and Late Life Telomere Length in the Health, Aging and Body Composition Study 
Brain, behavior, and immunity  2012;27(1):15-21.
Morbidity and mortality are greater among socially disadvantaged racial/ethnic groups and those of lower socioeconomic status (SES). Greater chronic stress exposure in disadvantaged groups may contribute to this by accelerating cellular aging, indexed by shorter age-adjusted telomere length. While studies consistently relate shorter leukocyte telomere length (LTL) to stress, the few studies, mostly from the UK, examining associations of LTL with SES have been mixed. The current study examined associations between educational attainment and LTL among 2,599 high-functioning black and white adults age 70-79 from the Health, Aging and Body Composition Study. Multiple regression analyses tested associations of race/ethnicity, educational attainment and income with LTL, adjusting for potential confounders. Those with only a high school education had significantly shorter mean LTL (4806 basepairs) than those with post-high school education (4926 basepairs; B=125, SE= 47.6, p = .009). A significant interaction of race and education (B = 207.8, SE = 98.7, p = .035) revealed more beneficial effects of post-high school education for blacks than for whites. Smokers had shorter LTL than non-smokers, but the association of education and LTL remained significant when smoking was covaried (B = 119.7, SE = 47.6, p = .012). While higher income was associated with longer LTL, the effect was not significant (p > .10). This study provides the first demonstration of an association between educational attainment and LTL in a US population where higher education appears to have a protective effect against telomere shortening, particularly in blacks.
doi:10.1016/j.bbi.2012.08.014
PMCID: PMC3543785  PMID: 22981835
Socioeconomic status; education; telomere length; race; health disparities
20.  Chronic stress elevates telomerase activity in rats 
Biology Letters  2012;8(6):1063-1066.
The enzyme telomerase lengthens telomeres—protective structures containing repetitive DNA sequences at chromosome ends. Telomere shortening is associated with diseases of ageing in mammals. Chronic stress has been related to shorter immune-cell telomeres, but telomerase activity under stress may be low, permitting telomere loss, or high, partially attenuating it. We developed an experimental model to examine the impacts of extended unpredictable stress on telomerase activity in male rats. Telomerase activity was 54 per cent higher in stressed rats than in controls, and associated with stress-related physiological and behavioural outcomes. This significant increase suggests a potential mechanism for resilience to stress-related replicative senescence.
doi:10.1098/rsbl.2012.0747
PMCID: PMC3497144  PMID: 23054915
chronic stress; telomere; telomerase; ageing; resilience
21.  Multisystem resiliency moderates the major depression–Telomere length association: Findings from the Heart and Soul Study 
Brain, behavior, and immunity  2013;33:10.1016/j.bbi.2013.05.008.
Major depressive disorder (MDD) has been associated with reduced leukocyte telomere length (LTL). It is not known, however, whether psychosocial and behavioral protective factors moderate this association. In the current study, we examine whether multisystem resiliency – defined by healthy emotion regulation, strong social connections, and health behaviors (sleep and exercise) – predicts LTL and mitigates previously demonstrated associations between depression diagnosis and LTL. LTL was measured, using a quantitative PCR assay, in 954 patients with stable cardiovascular disease in the Heart and Soul Study. In a fully adjusted model, high multisystem resiliency predicted longer LTL (b = 80.00, SE = 27.17, p = .003), whereas each individual factor did not. Multisystem resiliency significantly moderated the MDD-LTL association (p = .02). Specifically, MDD was significantly related to LTL at 1 SD below the mean of multisystem resiliency (b = −142.86, SE = 56.46, p = .01), but not at 1 SD above the mean (b = 49.07, SE = 74.51, p = .51). This study suggests that MDD associations with biological outcomes should be examined within a psychosocial–behavioral context, because this context shapes the nature of the direct relationship. Further research should explore the cognitive, neural, and other physiological pathways through which multisystem resiliency may confer biological benefit.
doi:10.1016/j.bbi.2013.05.008
PMCID: PMC3855878  PMID: 23727245
Major depressive disorder; Telomeres; Cell aging; Resiliency; Social connections; Emotion regulation; Physical activity
22.  An intricate dance: Life experience, multisystem resiliency, and rate of telomere decline throughout the lifespan 
Accumulation of life stressors predicts accelerated development and progression of diseases of aging. Telomere length, the DNA-based biomarker indicating cellular aging, is a mechanism of disease development, and is shortened in a dose response fashion by duration and severity of life stressor exposures. Telomere length captures the interplay between genetics, life experiences and psychosocial and behavioral factors. Over the past several years, psychological stress resilience, healthy lifestyle factors, and social connections have been associated with longer telomere length and it appears that these factors can protect individuals from stress-induced telomere shortening. In the current review, we highlight these findings, and illustrate that combining these `multisystem resiliency' factors may strengthen our understanding of aging, as these powerful factors are often neglected in studies of aging. In naturalistic studies, the effects of chronic stress exposure on biological pathways are rarely main effects, but rather a complex interplay between adversity and resiliency factors. We suggest that chronic stress effects can be best understood by directly testing if the deleterious effects of stress on biological aging processes, in this case the cell allostasis measure of telomere shortening, are mitigated in individuals with high levels of multisystem resiliency. Without attending to such interactions, stress effects are often masked and missed. Taking account of the cluster of positive buffering factors that operate across the lifespan will take us a step further in understanding healthy aging. While these ideas are applied to the telomere length literature for illustration, the concept of multisystem resiliency might apply to aging broadly, from cellular to systemic health.
doi:10.1111/j.1751-9004.2012.00465.x
PMCID: PMC3496269  PMID: 23162608
Telomeres; Cellular Allostatis; Life Stress; Psychological Stress Resiliency; Social Connections; Healthy Lifestyle Factors; Multisystem Resiliency
23.  Association between kidney function and telomere length: the Heart and Soul Study 
American journal of nephrology  2012;36(5):405-411.
Background
Telomere attrition is a novel risk factor for cardiovascular disease. Studies of telomere length in relation to kidney function are limited. We explored the association of kidney function with telomere length and telomere shortening.
Methods
The Heart and Soul study is a longitudinal study of patients with stable coronary heart disease (CHD). Measures of baseline kidney function included: serum creatinine, creatinine-derived estimated glomerular filtration rate (eGFRCKD-EPI), 24-hour urine measured creatinine clearance, cystatin C, cystatin C-derived estimated glomerular filtration rate (eGFRcys) and urine albumin to creatinine ratio. Telomere length was measured from peripheral blood leukocytes at baseline (N=954) and 5 years later (N=608). Linear regression models were used to test the association of kidney function with i) baseline telomere length and ii) change in telomere length over 5 years.
Results
At baseline, mean eGFRCKD-EPI was 72.6 (± 21.5) ml/min/1.73 m2, eGFRcys was 71.0 (± 23.1) ml/min/1.73 m2 and ACR was 8.6 (±12.3) mg/gm. Only lower baseline eGFRCKD-EPI was associated with shorter baseline telomere length (9.1 [95% CI 1.2–16.9] fewer base pairs for every 5 ml/min/1.73 m2 lower eGFRCKD-EPI). Lower baseline eGFRCKD-EPI (and all other measures of kidney function) predicted more rapid telomere shortening (10.8 [95% CI 4.3–17.3] decrease in base pairs over 5 years for every 5 ml/min/1.73 m2 lower eGFRCKD-EPI). After adjustment for age, these associations were no longer statistically significant.
Conclusions
In patients with CHD, reduced kidney function is associated with i) shorter baseline telomere length and ii) more rapid telomere shortening over 5 years, however these associations are entirely explained by older age.
doi:10.1159/000343495
PMCID: PMC3552638  PMID: 23108000
kidney; CKD; telomere
24.  Association Between Telomere Length and Experimentally Induced Upper Respiratory Viral Infection in Healthy Adults 
Importance
Although leukocyte telomere length is associated with mortality and many chronic diseases thought to be manifestations of age-related functional decline, it is not known whether it relates to acute disease in younger healthy populations.
Objective
To determine whether shorter telomeres in leukocytes, especially CD8CD28− T cells, are associated with decreased resistance to upper respiratory infection and clinical illness in young to midlife adults.
Design, Setting, and Participants
Between 2008 and 2011, telomere length was assessed in peripheral blood mononuclear cells (PBMCs) and T-cell subsets (CD4, CD8CD28+, CD8CD28−) from 152 healthy 18- to 55-year-old residents of Pittsburgh, Pennsylvania. Participants were subsequently quarantined (single rooms), administered nasal drops containing a common cold virus (rhinovirus 39), and monitored for 5 days for development of infection and clinical illness.
Main Outcome Measures
Infection (virus shedding or 4-fold increase in virus-specific antibody titer) and clinical illness (verified infection plus objective signs of illness).
Results
Rates of infections and clinical illness were 69% (n = 105) and 22% (n = 33), respectively. Shorter telomeres were associated with greater odds of infection, independent of prechallenge virus-specific antibody, demographics, contraceptive use, season, and body mass index (PBMC odds ratio [OR] per 1-SD decrease in telomere length, 1.71 [95% CI, 1.08–2.72]; n = 128 [shortest tertile 77% infected; middle, 66%; longest, 57%]; CD4: OR, 1.76 [95% CI, 1.15–2.70]; n = 146 [shortest tertile 80% infected; middle, 71%; longest, 54%]; CD8CD28+: OR, 1.93 [95% CI, 1.21–3.09], n = 132 [shortest tertile 84% infected; middle, 64%; longest, 58%]; CD8CD28-: OR, 2.02 [95% CI, 1.29–3.16]; n = 144 [shortest tertile 77% infected; middle, 75%; longest, 50%]). CD8CD28− was the only cell population in which shorter telomeres were associated with greater risk of clinical illness (OR, 1.69 [95% CI, 1.01–2.84]; n = 144 [shortest tertile, 26%; middle, 22%; longest, 13%]). The association between CD8CD28− telomere length and infection increased with age (CD8CD28− telomere length-X-age interaction, b = 0.09 [95% CI, 0.02–0.16], P = .01, n = 144).
Conclusion and Relevance
In this preliminary study among a cohort of healthy 18- to 55-year-olds, shorter CD8CD28− T-cell telomere length was associated with increased risk for experimentally induced acute upper respiratory infection and clinical illness.
doi:10.1001/jama.2013.613
PMCID: PMC3786437  PMID: 23423415
25.  Leptin concentrations in response to acute stress predict subsequent intake of comfort foods 
Physiology & behavior  2012;107(1):34-39.
Both animals and humans show a tendency toward eating more “comfort food” (high fat, sweet food) after acute stress. Such stress eating may be contributing to the obesity epidemic, and it is important to understand the underlying psychobiological mechanisms. Prior investigations have studied what makes individuals eat more after stress; this study investigates what might make individuals eat less. Leptin has been shown to increase following a laboratory stressor, and is known to affect eating behavior. This study examined whether leptin reactivity accounts for individual differences in stress eating. To test this, we exposed forty women to standardized acute psychological laboratory stress (Trier Social Stress Test) while blood was sampled repeatedly for measurements of plasma leptin. We then measured food intake after the stressor in 29 of these women. Increasing leptin during the stressor predicted lower intake of comfort food. These initial findings suggest that acute changes in leptin may be one of the factors modulating down the consumption of comfort food following stress.
doi:10.1016/j.physbeh.2012.04.021
PMCID: PMC3409346  PMID: 22579988

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