RESUMEN
OBJECTIVES: Human age-dependent telomere attrition and telomere shortening are associated with several age-associated diseases and poorer overall survival. The aim of this study was to determine longitudinal leucocyte telomere length dynamics and identify factors associated with temporal changes in telomere length. DESIGN AND METHODS: Leucocyte telomere length was measured by quantitative polymerase chain reaction in 8074 participants from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, an ongoing community-based prospective cohort study initiated in 1997. Follow-up data were available at two time-points up to 2007. Leucocyte telomere length was measured, on between one and three separate occasions, in a total of 16 783 DNA samples. Multilevel growth models were created to identify the factors that influence leucocyte telomere dynamics. RESULTS: We observed an average attrition rate of 0.47 ± 0.16 relative telomere length units (RTLUs) per year in the study population aged 48 (range 39-60) years at baseline. Annual telomere attrition rate increased with age (P < 0.001) and was faster on average in men than in women (P for interaction 0.043). The major independent factors determining telomere attrition rate were active smoking (approximately tripled the loss of RTLU per year, P < 0.0001) and multiple traits of the metabolic syndrome (waist-hip ratio, P = 0.007; blood glucose level, P = 0.045, and HDL cholesterol level, P < 0.001). CONCLUSIONS: Smoking and variables linked to the metabolic syndrome are modifiable lifestyle factors that accelerate telomere attrition in humans. The higher rate of cellular ageing may mediate the link between smoking and the metabolic syndrome to an increased risk of several age-associated diseases.
Asunto(s)
Senescencia Celular/genética , Fumar/efectos adversos , Acortamiento del Telómero , Adulto , Índice de Masa Corporal , Femenino , Humanos , Leucocitos , Masculino , Síndrome Metabólico/genética , Persona de Mediana Edad , Fumar/genética , Fumar/mortalidad , Telómero/genética , Acortamiento del Telómero/genéticaRESUMEN
BACKGROUND: Telomere length is considered an emerging marker of biological aging. Depression and anxiety are associated with excess mortality risk but the mechanisms remain obscure. Telomere length might be involved because it is associated with psychological distress and mortality. The aim of this study was to test whether anxiety and depressive disorders predict telomere length over time in a large population-based sample. Method All analyses were performed in a longitudinal study in a general population cohort of 974 participants. The Composite International Diagnostic Interview (CIDI) was used to measure the presence of anxiety and depressive disorders. Telomere length was measured using monochrome multiplex polymerase chain reaction (PCR) at approximately 2 years of follow-up. We used linear multivariable regression models to evaluate the association between anxiety and depressive disorders and telomere length, adjusting for adverse life events, lifestyle factors, educational level and antidepressant use. RESULTS: The presence of anxiety disorders predicted shorter telomeres at follow-up (ß = -0.073, t = -2.302, p = 0.022). This association was similar after controlling for adverse life events, lifestyle factors, educational level and antidepressant use (ß = -0.077, t = -2.144, p = 0.032). No association was found between depressive disorders and shorter telomeres at follow-up (ß = 0.010, t = 0.315, p = 0.753). CONCLUSIONS: This study found that anxiety disorders predicted shorter telomere length at follow-up in a general population cohort. The association was not explained by adverse life events, lifestyle factors, educational level and antidepressant use. How anxiety disorders might lead to accelerated telomere shortening and whether this might be a mediator explaining the excess mortality risk associated with anxiety deserve further investigation.
Asunto(s)
Trastornos de Ansiedad/epidemiología , Trastorno Depresivo/epidemiología , Leucocitos/ultraestructura , Estrés Psicológico/epidemiología , Acortamiento del Telómero , Telómero/ultraestructura , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Consumo de Bebidas Alcohólicas/epidemiología , Antidepresivos/uso terapéutico , Trastornos de Ansiedad/patología , Biomarcadores , Estudios de Cohortes , Trastorno Depresivo/patología , Escolaridad , Femenino , Conductas Relacionadas con la Salud , Humanos , Entrevista Psicológica , Acontecimientos que Cambian la Vida , Modelos Lineales , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex/métodos , Fumar/epidemiología , Factores de TiempoRESUMEN
The striking variability in the age of onset of and the manifestation/ absence of manifestation of cardiovascular diseases is inadequately explained by conventional risk factors, but may be explained by variation in biological age. Telomere length is possibly a reliable marker of biological age, shorter telomeres reflecting more advanced age. The initial telomere length ofa person is mainly determined by genetic factors. Moreover, the telomere length shortens with each cell division, and exposition to harmful environmental factors also results in shorter telomeres. Leukocytes of patients with atherosclerosis and heart failure display remarkably shorter telomeres compared to leukocytes of healthy subjects of similar age. Conventional cardiovascular risk factors are also associated with telomere length. If telomeres are indeed causally involved in the pathogenesis of cardiovascular disease, this might provide new avenues for future preventive and therapeutic strategies.