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Item Social connections, leukocyte telomere length, and all-cause mortality in older adults from Costa Rica : the Costa Rican longevity and healthy aging study (CRELES)(Journal of Aging and Health, DOI: 10.1177/08982643251313923, 2025) Gan, Danting; Baylin, Ana; Peterson, Karen E.; Rosero Bixby, Luis; Ruiz Narváez, Edward A.Objectives: To examine the association of social connections with blood leukocyte telomere length (LTL) and all-cause mortality in older Costa Ricans. Methods: Utilizing data from the Costa Rican Longevity and Healthy Aging Study (CRELES), a prospective cohort of 2827 individuals aged 60 and above followed since 2004, we constructed a Social Network Index (SNI) based on marital status, household size, interaction with non-cohabitating adult children, and church attendance. We used linear regression to assess SNI’s association with baseline LTL (N = 1113), and Cox proportional-hazard models to examine SNI’s relationship with all-cause mortality (N = 2735). Results: Higher SNI levels were associated with longer telomeres and decreased all-cause mortality during follow-up. Being married and regular church attendance were associated with 23% and 24% reductions of the all-cause mortality, respectively. Discussion: These findings underscore the importance of social engagement in promoting longevity among older Costa Ricans, suggesting broader implications for aging populations globally.Item Traditional rural dietary pattern and all-cause mortality in a prospective cohort study of elderly Costa Ricans: the Costa Rican Longevity and Healthy Aging Study (CRELES)(The American Journal of Clinical Nutrition, 2024) Zhang, Yundan; Cortés Ortiz, Mónica V.; Leung, Cindy W.; Baylin, Ana; Rosero Bixby, Luis; Ruiz Narváez, Edward A.Costa Rica, as many other Latin American countries, is experiencing a fast demographic aging. It is estimated that by 2030, 18.5% of the population, or almost 1 of every 5 Costa Ricans, will be 60 y or older, compared with 7.9% or 1 of every 13 Costa Ricans in 1999 [1]. As the population ages, chronic health conditions such as cardiovascular diseases (CVDs) and neurodegenerative disorders are expected to increase in prevalence posing growing challenges to the health of the Costa Rican population. With the demographic shift toward an aging population, there is an urgent need to study determinants of longevity and healthy aging. Diet—as part of a healthy lifestyle—is a key modifiable factor that may help to minimize the burden of age-related health conditions. Beans are a major source of protein and fiber in Costa Rican adults and part of traditional diets in most Latin American countries. High bean consumption has been found associated with a protective cardiometabolic prolife such as low total cholesterol and LDL cholesterol [2,3]. In the Costa Rican population specifically, intake of beans has been associated with lower risk of nonfatal myocardial infarction in middle-aged adults [4]. We recently reported that a traditional Costa Rican rural dietary pattern, rich in beans and rice, was associated with longer leukocyte telomeres—a marker of biologic aging—in Costa Rican adults 60 y and older [5]. However, no studies have examined whether adherence to a traditional diet in elderly Costa Ricans may also be associated with lower mortality. Because of the nutrition transition (i.e., a shift from traditional diets to an increased consumption of processed foods highs in sugars, fats, and salt) experienced by Costa Rica in the last decades [4,6,7], it is essential to evaluate the potential impact of traditional diets on promoting healthy aging and longevity within an aging population. In this study, we assessed the association between a traditional rural dietary pattern, as well as their major food components beans and rice, and all-cause mortality among elderly Costa Ricans aged 60 y and older at baseline. We hypothesized that higher scores on the traditional dietary pattern are associated with lower all-cause mortality in elderly Costa Ricans. We also assessed whether additional dietary patterns may be associated with all-cause mortality. We used longitudinal and nationally representative data from the Costa Rican Longevity and Healthy Aging Study (CRELES).Item 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.Item The vanishing advantage of longevity in Nicoya, Costa Rica: A cohort shif(Demographic Research, vol.49 (27, 2023) Rosero Bixby, LuisBACKGROUND The Nicoya region in Costa Rica has been identified as one of a handful of hotspots of extreme longevity. The evidence supporting this status comes mostly from observing the 1990 and 2000 decades and cohorts born before 1930. OBJECTIVE To determine how the longevity advantage of older men in Nicoya has progressed in the period 1990 to 2020 and in cohorts born from 1900 to 1950. METHODS Remaining length of life and adult mortality were estimated using new public administrative records from the electoral system and a Gompertz regression model. A new nationwide survival-time database of 550,000 adult Costa Ricans who were alive at any point during 1990–2020 was put together. RESULTS The longevity advantage of Nicoya is disappearing in a trend driven mostly by cohort effects. While Nicoyan males born in 1905 had 33% lower adult mortality rates than other Costa Ricans, those born in 1945 had 10% higher rates. The original geographic hotspot of low elderly mortality, coined the Nicoya blue zone, has decreased to a small area south of the peninsula around the corridor from Hojancha inland to the beach town of Sámara. However, Nicoyans born before 1930 who are still alive continue to show exceptionally high longevity. CONCLUSIONS Surviving Nicoyan males born before 1930 are exceptional human beings living longer than expected lives. Not so for more recent cohorts. The window of opportunity to meet and study pre-1930 individuals is closing.Item 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.Item Helicobacter pylori infection and serum pepsinogen concentrations in an elderly population representative of Costa Rica(Población y Salud en Mesoamérica 19(2), 2022) Une, Clas Allan; Malespín Bendaña, Wendy Karina; Ramírez Mayorga, Vanessa; Rosero Bixby, Luis; Sierra Ramos, RafaelaINTRODUCTION: Costa Rica has among the highest mortality rates from gastric cancer in the world, largely due to late detection. It is therefore important that economically and logistically sustainable screening is implemented in order to detect risk of developing cancer. We have previously shown that low pepsinogen (PG) values and infection with Helicobacter pylori-CagA+ are associated with risk of gastric atrophy and cancer in Costa Rican populations. OBJECTIVES: To determine how markers for gastric cancer risk are distributed in an elderly population representative of Costa Rica in order to design a screening strategy. METHODS: The population studied consists of 2,652 participants in a nationally representative survey of ageing. Information concerning epidemiologic, demographic, nutritional and life style factors is available. Serum PG concentrations as well as H. pylori and CagA status were determined by serology. Possible associations were determined by regression analyses. RESULTS: Antibodies to H. pylori were present in 72% of the population and of those, 58% were CagA positive. Infection with H. pylori was associated with higher PGI concentrations (p=0.000) and infection with H. pylori-CagA+ with lower PGI concentrations (p=0.025). Both showed association with lower PGI/PGII (p=0.006 and p=0.000). Higher age was associated with lower prevalence of H. pylori infection (OR=0.98; p=0.000) and CagA+ (OR=0.98; p=0.000) but not with PG values. Regions with high risk of gastric cancer showed lower PGI (p=0.004) and PGI/PGII values (p=0.021) as well as higher prevalence of H. pylori infection (OR=1.39; p=0.013) but not CagA+. Using cut-off values of PGI<100 μg/L and PGI/PGII<2.0, 2.5 and 3.0, 7-15% of the population would be considered at risk. CONCLUSIONS: H. pylori alone is not a useful marker for risk of gastric cancer. Screening using serum pepsinogen concentrations and infection with H. pylori-CagA+ is feasible in the general elderly population of Costa Rica but appropriate cut-off values have to be determined based on more clinical data and follow up capacity.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 Estudio longitudinal de mortalidad de adultos costarricenses 1984-2007(Población y Salud en Mesoamérica; Volumen 7, Número 2, 2010) Rosero Bixby, Luis; Antich Montero, DanielSe describen los procedimientos y se presentan algunos resultados del "estudio longitudinal de mortalidad de adultos costarricenses" (ELMAC), consistente en una muestra de cerca de 20.000 costarricenses de 30 o más años de edad del censo de población de 1984 seguidos hasta fines de 2007. El Instituto Nacional de Estadística y Censos (INEC) digitalizó los nombres de la boleta censal de los individuos en la muestra. Procesos informáticos depuraron los nombres y los enlazaron al número único de identificación -el número de cédula- del Registro Civil. El empate se efectuó en el 87% de la muestra. Los individuos identificados se siguieron en las bases de datos del Registro Civil para establecer su sobrevivencia. Se identificaron más de 5.000 defunciones entre el censo de 1984 y diciembre de 2007. Procesos informáticos adicionales enlazaron 92% de estas defunciones con las de las estadísticas vitales del INEC que contienen el dato de la causa de defunción. El patrón de mortalidad de la muestra, que comprende 373.000 personas-años de observación, reproduce bien las tasas de las tablas de mortalidad del país. Las gradientes socioeconómicas de la mortalidad en esta muestra no son sensibles a posibles errores en los empates o en las imputaciones efectuadas. La muestra confirma la excepcionalmente baja mortalidad de los adultos costarricenses, especialmente de los varones. Esta muestra abre la puerta para que se efectúen variedad de análisis de los determinantes socioeconómicos de la mortalidad de adultos en Costa Rica, algo rara vez intentado en un país en desarrollo.Item Generational Transfers and Population Aging in Latin America(Population and Development review 37 (Supplement), 2011) Rosero Bixby, LuisPopulation aging, a direct consequence of the demographic transition, is often portrayed in negative, even dire terms. This chapter examines some of the probable effects of population aging in Latin America within the framework of the National Transfer Accounts (NTA ) project (NTA 2010).1 The starting point is the NTA estimates of the life-cycle deficit and intergenerational transfers in five countries: Brazil, Chile, Costa Rica, Mexico, and Uruguay. This information is then combined with long-term demographic trends, primarily in age composition, to estimate expected effects on the economy. These effects, also known as “demographic dividends” (e.g., Mason and Lee 2007), are both positive and negative, meaning that population aging in the region involves not only challenges and constraints but also opportunities for development and gains in standards of living. In economic terms, the human life cycle typically includes long initial and final periods of dependency in which production, if any, is insufficient to meet consumption, and an intermediate period in which individuals produce more than they consume. The surplus in intermediate ages compensates for the “life-cycle deficit” at early and late ages through public and private transfers across generations, as well as through reallocations within the same generation. This cycle of deficit–surplus–deficit is neatly depicted by the age curves of consumption and production (labor income) in a given society (Lee, Mason, and Miller 2003).Item Predicting mortality with biomarkers : a population-based prospective cohort study for elderly Costa Ricans(Population Health Metrics 10(1), 2012) Rosero Bixby, Luis; Dow, William H.Background: Little is known about adult health and mortality relationships outside high-income nations, partly because few datasets have contained biomarker data in representative populations. Our objective is to determine the prognostic value of biomarkers with respect to total and cardiovascular mortality in an elderly population of a middle-income country, as well as the extent to which they mediate the effects of age and sex on mortality. Methods: This is a prospective population-based study in a nationally representative sample of elderly Costa Ricans. Baseline interviews occurred mostly in 2005 and mortality follow-up went through December 2010. Sample size after excluding observations with missing values: 2,313 individuals and 564 deaths. Main outcome: prospective death rate ratios for 22 baseline biomarkers, which were estimated with hazard regression models. Results: Biomarkers significantly predict future death above and beyond demographic and self-reprted health conditions. The studied biomarkers account for almost half of the effect of age on mortality. However, the sex gap in mortality became several times wider after controlling for biomarkers. The most powerful predictors were simple physical tests: handgrip strength, pulmonary peak flow, and walking speed. Three blood tests also predicted prospective mortality: C-reactive protein (CRP), glycated hemoglobin (HbA1c), and dehydroepiandrosterone sulfate (DHEAS). Strikingly, high blood pressure (BP) and high total cholesterol showed little or no predictive power. Anthropometric measures also failed to show significant mortality effects. Conclusions: This study adds to the growing evidence that blood markers for CRP, HbA1c, and DHEAS, along with organ-specific functional reserve indicators (handgrip, walking speed, and pulmonary peak flow), are valuable tools for identifying vulnerable elderly. The results also highlight the need to better understand an anomaly noted previously in other settings: despite the continued medical focus on drugs for BP and cholesterol, high levels of BP and cholesterol have little predictive value of mortality in this elderly population.
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