Claudia Lazarides1, Elissa S Epel2, Jue Lin3, Elizabeth H Blackburn3, Manuel C Voelkle4, Claudia Buss5, Hyagriv N Simhan6, Pathik D Wadhwa7, Sonja Entringer8. 1. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Psychological Medicine, Charitéplatz 1, 10117 Berlin, Germany. 2. Department of Psychiatry, University of California, San Francisco, CA, USA. 3. Department of Biochemistry & Biophysics, University of California, San Francisco, CA, USA. 4. Department of Psychology, Humboldt University, Berlin, Germany. 5. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Psychological Medicine, Charitéplatz 1, 10117 Berlin, Germany; Department of Pediatrics, University of California, Irvine, CA 92617, USA; Development, Health and Disease Research Program, University of California, Irvine, CA 92617, USA. 6. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA. 7. Department of Psychiatry & Human Behavior, University of California, Irvine, CA 92617, USA; Department of Pediatrics, University of California, Irvine, CA 92617, USA; Department of Obstetrics & Gynecology, University of California, Irvine, CA 92617, USA; Department of Epidemiology, University of California, Irvine, CA 92617, USA; Development, Health and Disease Research Program, University of California, Irvine, CA 92617, USA. Electronic address: pwadhwa@uci.edu. 8. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Psychological Medicine, Charitéplatz 1, 10117 Berlin, Germany; Department of Pediatrics, University of California, Irvine, CA 92617, USA; Development, Health and Disease Research Program, University of California, Irvine, CA 92617, USA. Electronic address: sonja.entringer@charite.de.
Abstract
INTRODUCTION: Telomere biology plays a fundamental role in maintaining the integrity of the genome and cell, and shortened telomeres have been linked to several age-related diseases. The initial (newborn) telomere length (TL) represents a critically important feature of the telomere biology system. Exposure to a variety of adverse prenatal conditions such as maternal stress, suboptimal diet, obesity, and obstetric complications, is associated with shorter offspring TL at birth and in adult life. Many, if not all, of these exposures are believed to have an inflammatory component. In this context, stress-related immunological processes during pregnancy may constitute a potential additional biological pathway because they can affect telomere length and telomerase activity via transcriptions factors such as cyclic adenosine monophosphate-dependent transcription factor (ATF7) and nuclear factor-kappa B (NF-κB). Thus, in the present study we examined the hypothesis that maternal pro-inflammatory state across pregnancy, operationalized as the balance between tumor necrosis factor (TNF)-α, a major pro-inflammatory cytokine, and interleukin-10 (IL-10), the major anti-inflammatory cytokine, is associated with newborn leukocyte telomere length (LTL) at birth. METHODS AND MATERIALS: Participants were healthy women (N = 112) recruited in early pregnancy. Concentrations of TNF- α and IL-10 were quantified in early, mid and late pregnancy from maternal blood samples. Telomere length was assessed in newborn blood samples soon after birth. RESULTS: After adjusting for maternal age, maternal pre-pregnancy BMI, birth weight percentile, and infant sex, a higher mean TNF-α/IL-10 ratio across pregnancy was significantly associated with shorter newborn TL (β = -.205, p = .030). Newborn TL was, on average, 10% shorter in offspring of women in the upper compared to lower quartile of the TNF-α/IL-10 ratio during pregnancy. DISCUSSION: These findings provide new evidence in humans for a potential "programming" mechanism linking maternal systemic pro-inflammatory processes during pregnancy with the initial (newborn) setting of her offspring's telomere system.
INTRODUCTION: Telomere biology plays a fundamental role in maintaining the integrity of the genome and cell, and shortened telomeres have been linked to several age-related diseases. The initial (newborn) telomere length (TL) represents a critically important feature of the telomere biology system. Exposure to a variety of adverse prenatal conditions such as maternal stress, suboptimal diet, obesity, and obstetric complications, is associated with shorter offspring TL at birth and in adult life. Many, if not all, of these exposures are believed to have an inflammatory component. In this context, stress-related immunological processes during pregnancy may constitute a potential additional biological pathway because they can affect telomere length and telomerase activity via transcriptions factors such as cyclic adenosine monophosphate-dependent transcription factor (ATF7) and nuclear factor-kappa B (NF-κB). Thus, in the present study we examined the hypothesis that maternal pro-inflammatory state across pregnancy, operationalized as the balance between tumor necrosis factor (TNF)-α, a major pro-inflammatory cytokine, and interleukin-10 (IL-10), the major anti-inflammatory cytokine, is associated with newborn leukocyte telomere length (LTL) at birth. METHODS AND MATERIALS: Participants were healthy women (N = 112) recruited in early pregnancy. Concentrations of TNF- α and IL-10 were quantified in early, mid and late pregnancy from maternal blood samples. Telomere length was assessed in newborn blood samples soon after birth. RESULTS: After adjusting for maternal age, maternal pre-pregnancy BMI, birth weight percentile, and infant sex, a higher mean TNF-α/IL-10 ratio across pregnancy was significantly associated with shorter newborn TL (β = -.205, p = .030). Newborn TL was, on average, 10% shorter in offspring of women in the upper compared to lower quartile of the TNF-α/IL-10 ratio during pregnancy. DISCUSSION: These findings provide new evidence in humans for a potential "programming" mechanism linking maternal systemic pro-inflammatory processes during pregnancy with the initial (newborn) setting of her offspring's telomere system.
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