Examinando por Autor "Rehkopf, David H."
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Ítem 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.Ítem Centenarian clocks: epigenetic clocks for validating claims of exceptional longevity(SPRINGER LINK, vol. 45, 2023) Dec, Eric; Clement, James; Cheng, Kaiyang; Church, George M.; Fossel, Michael B.; Rehkopf, David H.; Rosero Bixby, Luis; Kobor, Michael S.; Lin, David TS.; Lu, Ake T.; Fei, Zhe; Guo, Wei; Chew, Yap Ching; Yang, Xiaojing; Dwi Putra, Sulistyo E.; Reiner, Alex P.; Correa, Adolfo; Vilalta, Adrian; Pirazzini, Chiara; Passarino, Giuseppe; Monti, Daniela; Arosio, Beatrice; Garagnani, Paolo; Franceschi, Claudio; Horvath, SteveClaims surrounding exceptional longevity are sometimes disputed or dismissed for lack of credible evidence. Here, we present three DNA methylation-based age estimators (epigenetic clocks) for verifying age claims of centenarians. The three centenarian clocks were developed based on n = 7039 blood and saliva samples from individuals older than 40, including n = 184 samples from centenarians, 122 samples from semi-supercentenarians (aged 105 +), and 25 samples from supercentenarians (aged 110 +). The oldest individual was 115 years old. Our most accurate centenarian clock resulted from applying a neural network model to a training set composed of individuals older than 40. An epigenome- wide association study of age in different age groups revealed that age effects in young individuals (age < 40) are correlated (r = 0.55) with age effects in old individuals (age > 90). We present a chromatin state analysis of age effects in centenarians. The centenarian clocks are expected to be useful for validating claims surrounding exceptional old age.Ítem Correlates of longitudinal leukocyte telomere length in the Costa Rican Longevity Study of Healthy Aging (CRELES): On the importance of DNA collection and storage procedures(PLoS ONE, vol.14(10), 2019) Rosero Bixby, Luis; Rehkopf, David H.; Dow, William H.; Lin, Jue; Epel, Elissa S.; Azofeifa Navas, Jorge; Leal Esquivel, AlejandroThe objective is to identify cofactors of leukocyte telomere length (LTL) in a Latin American population, specifically the association of LTL with 36 socio-demographic, early childhood, and health characteristics, as well as with DNA sample collection and storage procedures. The analysis is based on longitudinal information from a subsample of 1,261 individuals aged 60+ years at baseline from the Costa Rican Study of Longevity and Healthy Aging (CRELES): a nationally representative sample of elderly population. Random effects regression models for panel data were used to estimate the associations with LTL and its longitudinal changes. Sample collection procedures and DNA refrigerator storage time were strongly associated with LTL: telomeres are longer in blood collected in October-December, in DNA extracted from <1-year-old blood cells, and in DNA stored at 4°C for longer periods of time up to five years. The data confirmed that telomeres are shorter at older ages, as well as among males, and diabetic individuals, whereas telomeres are longer in the high-longevity Nicoya region. Most health, biomarkers, and early childhood indicators did not show significant associations with LTL. Longitudinal LTL variation over approximately two years was mainly associated with baseline LTL levels, as found in other studies. Our findings suggest that if there is unavoidable variability in season of sample collection and DNA storage time, these factors should be controlled for in all demographic and epidemiologic studies of LTL. However, due to unobserved components of measurement variation, statistical control may be inadequate as compared to standardization of data collection procedures.Ítem Differences in the association of cardiovascular risk factors with education: a comparison of Costa Rica (CRELES) and the USA (NHANES)(J Epidemiol Community Health 2010: 64, 2009) Rehkopf, David H.; Dow, William H.; Rosero Bixby, LuisBackground Despite different levels of economic development, Costa Rica and the USA have similar mortalities among adults. However, in the USA there are substantial differences in mortality by educational attainment, and in Costa Rica there are only minor differences. This contrast motivates an examination of behavioural and biological correlates underlying this difference. Methods The authors used data on adults aged 60 and above from the Costa Rican Longevity and Healthy Ageing Study (CRELES) (n¼2827) and from the US National Health and Nutrition Examination Survey (NHANES) (n¼5607) to analyse the cross-sectional association between educational level and the following risk factors for cardiovascular disease (CVD): ever smoked, current smoker, sedentary, high saturated fat, high carbohydrates, high calorie diet, obesity, severe obesity, large waist circumference, HDL cholesterol, LDL cholesterol, triglycerides, hemoglobin A1c, fasting glucose, C-reactive protein, systolic blood pressure and BMI. Results There were significantly fewer hazardous levels of risk biomarkers at higher levels of education for more than half (10 out of 17) of the risk factors in the USA, but for less than a third of the outcomes in Costa Rica (five out of 17). Conclusions These results are consistent with the context-specific nature of educational differences in risk factors for CVD and with a non-uniform nature of association of CVD risk factors with education within countries. Our results also demonstrate that social equity in mortality is achieved without uniform equity in all risk factors.Ítem 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 methylationÍtem Epigenome-Wide Association Study and Epigenetic Age Acceleration Associated with Cigarette Smoking among Costa Rican Adults(Scientific Reports, Vol. 12 Núm, 2022) Cárdenas, Andrés; Ecker, Simone; Fadadu, Raj P.; Huen, Karen; Orozco, Allan; McEwen, Lisa M.; Engelbrecht, Hannah Ruth; Gladish, Nicole; Kobor, Michael S.; Rosero Bixby, Luis; Dow, William H.; Rehkopf, David H.Smoking-associated DNA methylation (DNAm) signatures are reproducible among studies of mostly European descent, with mixed evidence if smoking accelerates epigenetic aging and its relationship to longevity. We evaluated smoking-associated DNAm signatures in the Costa Rican Study on Longevity and Healthy Aging (CRELES), including participants from the high longevity region of Nicoya. We measured genome-wide DNAm in leukocytes, tested Epigenetic Age Acceleration (EAA) from five clocks and estimates of telomere length (DNAmTL), and examined effect modification by the high longevity region. 489 participants had a mean (SD) age of 79.4 (10.8) years, and 18% were from Nicoya. Overall, 7.6% reported currently smoking, 35% were former smokers, and 57.4% never smoked. 46 CpGs and five regions (e.g. AHRR, SCARNA6/SNORD39, SNORA20, and F2RL3) were differentially methylated for current smokers. Former smokers had increased Horvath’s EAA (1.69-years; 95% CI 0.72, 2.67), Hannum’s EAA (0.77-years; 95% CI 0.01, 1.52), GrimAge (2.34-years; 95% CI1.66, 3.02), extrinsic EAA (1.27-years; 95% CI 0.34, 2.21), intrinsic EAA (1.03-years; 95% CI 0.12, 1.94) and shorter DNAmTL (− 0.04-kb; 95% CI − 0.08, − 0.01) relative to non-smokers. There was no evidence of effect modification among residents of Nicoya. Our findings recapitulate previously reported and novel smoking-associated DNAm changes in a Latino cohort.Ítem Life-course BMI and biomarkers in persons aged 60 years or older: a comparison of the USA and Costa Rica(Public Health Nutrition, vol.22(2), 2019) Rehkopf, David H.; Duong, Andrew; Dow, William H.; Rosero Bixby, LuisObjective: There is a large literature linking current body mass index (BMI) to levels of cardiovascular risk biomarkers, but it is unknown whether measures of BMI earlier in the life course and maximum BMI are predictive of current levels of biomarkers. The objective of this study is to determine how current, maximum and age 25 body mass index among individuals over the age of 60 are associated with their current levels of cardiovascular risk biomarkers. Design: Cross-sectional study with retrospective recall. Setting: Costa Rica (n=821) and the United States (n=4110). Subjects: Nationally representative samples of adults aged 60 and over. Results: We used regression models to examine the relationship between multiple meaures of body mass index with four established cardiovascular risk biomarkers. The most consistent predictor of current levels of systolic blood pressure, triglycerides and HDL cholesterol is current BMI. However, maximum BMI is the strongest predictor of hemoglobin A1c and is also related to HDL cholesterol and triglycerides. Hemoglobin A1c is independent of current BMI. We find that these relationships are consistent between Costa Rica and the United States for hemoglobin A1c and for HDL cholesterol. Conclusions: Current levels of cardiovascular risk biomarkers are not only the product of current levels of BMI, but also of maximum lifetime BMI, in particular for levels of hemoglobin A1c and for HDL cholesterol. Managing maximum obtained BMI over the life course may be most critical for maintaining the healthiest levels of cardiovascular risk.Ítem 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.Ítem Predicting survival from telomere length versus conventional predictors: a multinational population-based cohort study(PLOS One; Volumen 11, Número 4, 2016) Glei, Dana; Risques, Rosa Ana; Rehkopf, David H.; Dow, William H.; Rosero Bixby, Luis; Weinstein, Maxine; Goldman, NoreenTelomere length has generated substantial interest as a potential predictor of aging- related diseases and mortality. Some studies have reprted significant associations, but few have tested its ability to discriminate between decedents and survivors compared with a broad range of well-established predictors that include both biomarkers and commonly collected self-reprted data. Our aim here was to quantify the prognostic value of leuko- cyte telomere length relative to age, sex, and 19 other variables for predicting five-year mortality among older persons in three countries. We used data from nationally represen- tative surveys in Costa Rica (N = 923, aged 61+), Taiwan (N = 976, aged 54+), and the U. S. (N = 2672, aged 60+). Our study used a prospective cohort design with all-cause mor- tality during five years post-exam as the outcome. We fit Cox hazards models separately by country, and assessed the discriminatory ability of each predictor. Age was, by far, the single best predictor of all-cause mortality, whereas leukocyte telomere length was only somewhat better than random chance in terms of discriminating between decedents and survivors. After adjustment for age and sex, telomere length ranked between 15th and 17th (out of 20), and its incremental contribution was small; nine self-reprted variables (e.g., mobility, global self-assessed health status, limitations with activities of daily living, smoking status), a cognitive assessment, and three biological markers (C-reactive protein, serum creatinine, and glycosylated hemoglobin) were more powerful predictors of mortality in all three countries. Results were similar for cause-specific models (i.e., mortality from cardiovascular disease, cancer, and all other causes combined). Leukocyte telomere length had a statistically discernible, but weak, association with mortality, but it did not predict survival as well as age or many other self-reprted variables. Although telomere length may eventually help scientists understand aging, more powerful and more easily obtained tools are available for predicting survival.Ítem 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.Ítem The Nicoya region of Costa Rica : a high longevity island for elderly males(Vienna Yearbook of Population Research, Vol 11, 2013) Rosero Bixby, Luis; Dow, William H.; Rehkopf, David H.Reliable data show that the Nicoyan region of Costa Rica is a hot spot of high longevity. A survival follow-up of 16,300 elderly Costa Ricans estimated a Nicoya death rate ratio (DRR) for males 1990–2011 of 0.80 (0.69–0.93 CI). For a 60-yearold Nicoyan male, the probability of becoming centenarian is seven times that of a Japanese male, and his life expectancy is 2.2 years greater. This Nicoya advantage does not occur in females, is independent of socio-economic conditions, disappears in out-migrants and comes from lower cardiovascular (CV) mortality (DRR = 0.65). Nicoyans have lower levels of biomarkers of CV risk; they are also leaner, taller and suffer fewer disabilities. Two markers of ageing and stress—telomere length and dehydroepiandrosterone sulphate—are also more favourable. The Nicoya diet is prosaic and abundant in traditional foods like rice, beans and animal protein, with low glycemic index and high fibre content.