Dysregulated physiological stress systems and accelerated cellular aging

D. Révész, J. Verhoeven, Y. Milaneschi, E.J.C. de Geus, O.M. Wolkowitz, B.W.J.H. Penninx

Research output: Contribution to JournalArticleAcademicpeer-review


Exposure to chronic stressors is associated with accelerated biological aging as indicated by reduced leukocyte telomere length (LTL). This impact could be because of chronic overactivation of the body's physiological stress systems. This study examined the associations between LTL and the immune system, hypothalamic-pituitary-adrenal axis and autonomic nervous system. LTL was assessed in 2936 adults from the Netherlands Study of Depression and Anxiety. Inflammation markers (interleukin-6, c-reactive protein, tumor necrosis factor-alpha), hypothalamic-pituitary-adrenal-axis indicators (salivary cortisol awakening curve [area under the curve indicators, with respect to the ground and increase], evening levels, 0.5 mg dexamethasone cortisol suppression ratio), and autonomic nervous system measures (heart rate, respiratory sinus arrhythmia, pre-ejection period) were determined. Linear regression analyses were performed and adjusted for sociodemographic, lifestyle and clinical factors. Shorter LTL was significantly associated with higher c-reactive protein, interleukin-6, area under the curve with respect to increase, and heart rate. A cumulative index score was calculated based on the number of highest tertiles of these 4 stress markers. LTL demonstrated a significant gradient within subjects ranging from having zero (5528base pairs) to having 4 elevated stress markers (5371base pairs, p for trend= 0.002), corresponding to a difference of 10years of accelerated biological aging. Contrary to the expectations, shorter LTL was also associated with longer pre-ejection period, indicating lower sympathetic tone. This large-scale study showed that inflammation, high awakening cortisol response, and increased heart rate are associated with shorter LTL, especially when they are dysregulated cumulatively. © 2014 Elsevier Inc.
Original languageEnglish
Pages (from-to)1422-1430
Number of pages9
JournalNeurobiology of Aging
Issue number6
Publication statusPublished - 2014


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