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Item Stressors over the life course and neuroendocrine system dysregulation in Costa Rica(Journal of Aging and Health XX(X), 2010) Gersten, Omer; Rosero Bixby, Luis; Dow, William H.Objectives: A key aspect of the increasingly popular allostatic load (AL) framework is that stressors experienced over the entire life course result in physiological dysregulation. Although core to AL theory, this idea has been little tested, and where it has been tested, the results have been mixed. Method: The study analyzes the Costa Rican Study on Longevity and Healthy Aging (CRELES), a new, cross-sectional, and nationally representative survey of older Costa Rican men and women (aged between 60 and 109 years). The survey period is between 2004 and 2006, and the survey has a sample size of 2,827 individuals. This article focuses on the relationship between a variety of stressors experienced over the life course and cortisol, dehydroepiandrosterone sulfate (DHEAS), epinephrine, and norepinephrine analyzed separately and in an index. Results: There are some links between certain stressors and worse cortisol levels, but overall, almost all of the stressors examined are not associated with riskier neuroendocrine biomarker profiles. Discussion: More work is needed, in order to establishthe connection between stressors experienced over the life course and resting levels of the neuroendocrine markers.Item Longer leukocyte telomere length in Costa Rica's Nicoya Peninsula: A population-based study(Experimental Gerontology; Volumen 48, Número 11, 2013) Rehkopf, David H.; Dow, William H.; Rosero Bixby, Luis; Lin, Jue; Epel, Elissa S.; Blackburn, Elizabeth H.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.Item Seasonal variation of peripheral blood leukocyte telomere length in Costa Rica : a population-based observational study(American Journal of Human Biology; Volumen 26, Número 3, 2014) Rehkopf, David H.; Dow, William H.; Rosero Bixby, Luis; Lin, Jue; Epel, Elissa S.; Blackburn, Elizabeth H.Objectives: Peripheral blood leukocyte telomere length (LTL) 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 LTL. We examined whether there was monthly variation in LTL 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. LTL was assayed from these samples using the quantitative PCR method. Multivariate regression models were used to examine correlations between month of blood draw and LTL. 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 LTL. 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 LTL use methods to account for the potential impact of constituent cell type.Item A cross-national comparison of 12 biomarkers finds no universal biomarkers of aging among individuals aged 60 and older(Vienna Yearbook of Population Research, vol.14, 2016) Rehkopf, David H.; Rosero Bixby, Luis; Dow, William H.There is uncertainty about whether biological and anthropometric measures that are clinical risk factors for disease are universally associated with chronological age, or whether these correlations vary depending on the social and economic context. The answer to this question has implications for the malleability of biological aging. To examine this issue, we use population-based data on individuals aged 60 and older from the Costa Rican Study on Longevity and Healthy Aging, and temporally consistent data from the United States National Health and Nutrition Examination Survey and the United States Health and Retirement Study. Our analysis focuses on 12 biomarkers that have been shown in the literature to have an association with age, and that occur prior to the clinical manifestation of disease. We find that there are few consistent patterns of association with age when these biomarkers are stratified by gender, country, and level of education. This result suggests that these measures of biological aging are highly context-dependent, and that none of the 12 biomarkers we examined are universal biomarkers of aging. Future research that investigates composite measures of biological age should test newly proposed measures across gender, social class, and country.Item Differential DNA methylation and lymphocyte proportions in a Costa Rican high longevity region(Epigenetics & Chromatin,vol.10(21), 2017) McEwen, Lisa M.; Morin, Alexander M.; Edgar, Rachel D.; MacIsaac, Julia L.; Jones, Meaghan J.; Dow, William H.; Rosero Bixby, Luis; Kobor, Michael S.; Rehkopf, David H.Background: The Nicoya Peninsula in Costa Rica has one of the highest old-age life expectancies in the world, but the underlying biological mechanisms of this longevity are not well understood. As DNA methylation is hypothesized to be a component of biological aging, we focused on this malleable epigenetic mark to determine its association with current residence in Nicoya versus elsewhere in Costa Rica. Examining a population’s unique DNA methylation pattern allows us to differentiate hallmarks of longevity from individual stochastic variation. These differences may be characteristic of a combination of social, biological, and environmental contexts. Methods: In a cross-sectional subsample of the Costa Rican Longevity and Healthy Aging Study, we compared whole blood DNA methylation profiles of residents from Nicoya (n = 48) and non-Nicoya (other Costa Rican regions, n = 47) using the Infinium HumanMethylation450 microarray. Results: We observed a number of differences that may be markers of delayed aging, such as bioinformatically derived differential CD8+ T cell proportions. Additionally, both site- and region-specific analyses revealed DNA methylation patterns unique to Nicoyans. We also observed lower overall variability in DNA methylation in the Nicoyan population, another hallmark of younger biological age. Conclusions: Nicoyans represent an interesting group of individuals who may possess unique immune cell proportions as well as distinct differences in their epigenome, at the level of DNA methylationItem Costa Rican Longevity and Healthy Aging Study(Encyclopedia of Gerontology and Population Aging. Springer Cham, 2019) Rosero Bixby, Luis; Dow, William H.; Brenes Camacho, GilbertThe Costa Rican Longevity and Healthy Aging Study (CRELES, or Costa Rica Estudio de Longevidad y Envejecimiento Saludable) is a set of nationally representative longitudinal surveys of health and life-course experiences of older Costa Ricans, conducted by the University of Costa Rica’s Centro Centroamericano de Población in collaboration with the University of California at Berkeley. CRELES is part of the growing set of Health and Retirement Surveys being conducted around the world (See “Health and Retirement Study”). Costa Rica is of particular interest to study given its high longevity: life expectancy is greater than that of the United States, despite being a middle-income country. CRELES comprises five waves of data from two birth cohort panels (See “Cross-Sectional Research/Panel Studies (Longitudinal Studies)”). The original CRELES Pre-1945 cohort is a sample of more than 2,800 Costa Rica residents born in 1945 or before. There are three waves of interviews for this panel conducted mainly in 2005, 2007, and 2009. Wellcome Trust funded this panel (Grant N. 072406). The CRELES 1945–1955 Retirement Cohort (RC) is a sample of about 2800 Costa Rica residents born in 1945–1955 plus 1400 of their spouses, interviewed mainly in 2011 and 2013 (waves 4 and 5). The US National Institute on Aging (grant R01AG031716) funded this panel through the University of California, Berkeley. CRELES data are well-suited for studying longevity and health determinants, relationships between socioeconomic status and health, stress and health, patterns of health behaviors, and prospective mortality.