RESUMO
Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from 8 prospective population-based cohort studies, representing 13 021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had excess mortality from all causes of 57 deaths per 10 000 person-years (95% confidence interval [CI]: 38, 76) compared with their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10 000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the World Health Organization (WHO) risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.
Assuntos
Epigênese Genética , Epigenômica , Escolaridade , Feminino , Humanos , Masculino , Mortalidade , Estudos Prospectivos , Fatores de Risco , Fatores SocioeconômicosRESUMO
RESUMEN Objetivo Modelar el curso de la pandemia COVID-19 en Chile y proyectar la demanda de recursos hospitalarios y letalidad en escenarios simulados: primero, recurriendo a distintas medidas de mitigación para contener la propagación en un mes -desde el 14 de abril hasta el 14 de mayo del 2020- y, segundo, en el supuesto contagio del 70% de la población, según edad, sin límite de tiempo. Métodos Utilizamos como base el número de contagios confirmados con SARS-CoV-2 en Chile hasta el 14 de abril del 2020 (8 273 casos, 94 muertes). Para los distintos escenarios, asumimos un número reproductivo básico que va desde R0=2,5 hasta R0=1,5. La proyección de la demanda hospitalaria y letalidad por edad se fundamentaron en reportes italianos y británicos. Resultados Estimamos que para el 14 de mayo del 2020 habría en Chile 2 019 775 contagiados y 15 068 fallecidos en ausencia de medidas de mitigación (R0=2,5). Al implementar medidas que reduzcan R0 a 1,5 (detección temprana y aislamiento de casos, cuarentena y distanciamiento social de mayores de 70 años), el número de contagios y letalidad disminuirían a 94 235 y 703 respectivamente. Sin embargo, la demanda hospitalaria aún sobrepasaría la capacidad de respuesta. La población de mayor riesgo la componen los mayores de 60 años. Conclusión Encontramos evidencia a favor de las medidas de mitigación implementadas por el Gobierno chileno. Sin embargo, medidas más estrictas son necesarias para no colapsar el sistema sanitario, que cuenta con menos recursos hospitalarios que los proyectados. Es esencial aumentar la capacidad hospitalaria en términos de equipamiento y entrenamiento del personal de salud.(AU)
ABSTRACT Objetive To model disease progression, healthcare demand and case fatality rate attributed to COVID-19 pandemic that may occur in Chile in 1-month time, by simulating different scenarios according to diverse mitigation measures hypothetically implemented. Furthermore, we aimed to estimate the same outcomes assuming that 70% of the population will be infected by SARS-CoV-2, with no time limit assumption. Methods We based on the number of confirmed COVID-19 cases in Chile up to April 14th 2020 (8 273 cases and 94 deaths). For the simulated scenarios we assumed basic reproduction numbers ranging from R0=2.5 to R0=1.5. The estimation of the number of patients that would require intensive care and the age-specific case fatality rate were based on data provided by the Imperial College of London and the Instituto Superiore di Sanità en Italia. Results If no mitigation measures were applied (R0=2.5), by May 25, Chile would have 2 019 775 cases and 15 068 deaths. If mitigations measures were implemented to decrease R0 to 1.5 (early detection of cases, quarantine, social distancing of elderly), the number of cases and deaths would importantly decrease. Nonetheless, the demand for in-hospital care including intensive care would exceed the available resources. Our age-specific analysis showed that population over 60 years are at higher risk of needing intensive care and death. Conclusion Our evidence supports the mitigation measures implemented by the Chilean government. Nevertheless, more stringent measures are needed to prevent the health care system's collapse due to shortfall of resources to confront the COVID-19 pandemic.(AU)
Assuntos
Humanos , Sistemas de Saúde/organização & administração , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/epidemiologia , /métodos , Chile/epidemiologiaRESUMO
Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life.We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries.The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect.Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.
