Longevidad
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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 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.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 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 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.