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      Childhood Adversities Are Associated with Shorter Telomere Length at Adult Age both in Individuals with an Anxiety Disorder and Controls

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          Abstract

          Accelerated leukocyte telomere shortening has been previously associated to self-perceived stress and psychiatric disorders, including schizophrenia and mood disorders. We set out to investigate whether telomere length is affected in patients with anxiety disorders in which stress is a known risk factor. We also studied the effects of childhood and recent psychological distress on telomere length. We utilized samples from the nationally representative population-based Health 2000 Survey that was carried out between 2000–2001 in Finland to assess major public health problems and their determinants. We measured the relative telomere length of the peripheral blood cells by quantitative real-time PCR from 321 individuals with DSM-IV anxiety disorder or subthreshold diagnosis and 653 matched controls aged 30–87 years, who all had undergone the Composite International Diagnostic Interview. While telomere length did not differ significantly between cases and controls in the entire cohort, the older half of the anxiety disorder patients (48–87 years) exhibited significantly shorter telomeres than healthy controls of the same age (P = 0.013). Interestingly, shorter telomere length was also associated with a greater number of reported childhood adverse life events, among both the anxiety disorder cases and controls (P = 0.005). Childhood chronic or serious illness was the most significantly associated single event affecting telomere length at the adult age (P = 0.004). Self-reported current psychological distress did not affect telomere length. Our results suggest that childhood stress might lead to accelerated telomere shortening seen at the adult age. This finding has potentially important implications supporting the view that childhood adversities might have a considerable impact on well being later in life.

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          Most cited references48

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          Oxidative stress shortens telomeres.

          Telomeres in most human cells shorten with each round of DNA replication, because they lack the enzyme telomerase. This is not, however, the only determinant of the rate of loss of telomeric DNA. Oxidative damage is repaired less well in telomeric DNA than elsewhere in the chromosome, and oxidative stress accelerates telomere loss, whereas antioxidants decelerate it. I suggest here that oxidative stress is an important modulator of telomere loss and that telomere-driven replicative senescence is primarily a stress response. This might have evolved to block the growth of cells that have been exposed to a high risk of mutation.
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            Telomeres and human disease: ageing, cancer and beyond.

            Telomere length and telomerase activity are important factors in the pathobiology of human disease. Age-related diseases and premature ageing syndromes are characterized by short telomeres, which can compromise cell viability, whereas tumour cells can prevent telomere loss by aberrantly upregulating telomerase. Altered functioning of both telomerase and telomere-interacting proteins is present in some human premature ageing syndromes and in cancer, and recent findings indicate that alterations that affect telomeres at the level of chromatin structure might also have a role in human disease. These findings have inspired a number of potential therapeutic strategies that are based on telomerase and telomeres.
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              Obesity, cigarette smoking, and telomere length in women.

              Obesity and smoking are important risk factors for many age-related diseases. Both are states of heightened oxidative stress, which increases the rate of telomere erosion per replication, and inflammation, which enhances white blood cell turnover. Together, these processes might accelerate telomere erosion with age. We therefore tested the hypothesis that increased body mass and smoking are associated with shortened telomere length in white blood cells. We investigated 1122 white women aged 18-76 years and found that telomere length decreased steadily with age at a mean rate of 27 bp per year. Telomeres of obese women were 240 bp shorter than those of lean women (p=0.026). A dose-dependent relation with smoking was recorded (p=0.017), and each pack-year smoked was equivalent to an additional 5 bp of telomere length lost (18%) compared with the rate in the overall cohort. Our results emphasise the pro-ageing effects of obesity and cigarette smoking.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2010
                25 May 2010
                : 5
                : 5
                : e10826
                Affiliations
                [1 ]Research Program of Molecular Neurology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
                [2 ]Department of Medical Genetics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
                [3 ]Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
                [4 ]FIMM, Institute of Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
                [5 ]Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
                [6 ]Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland
                [7 ]The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America
                [8 ]Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
                Leicester University, United Kingdom
                Author notes

                Conceived and designed the experiments: IH. Performed the experiments: LK IH. Analyzed the data: LK IS SP JS SR IH. Contributed reagents/materials/analysis tools: SP JS JL LP SR IH. Wrote the paper: LK SR IH.

                Article
                10-PONE-RA-16308R1
                10.1371/journal.pone.0010826
                2876034
                20520834
                9e87589c-d986-4671-be27-0f5d561259ce
                Kananen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 15 February 2010
                : 5 May 2010
                Page count
                Pages: 7
                Categories
                Research Article
                Genetics and Genomics/Chromosome Biology
                Genetics and Genomics/Complex Traits
                Mental Health/Neuropsychiatric Disorders

                Uncategorized
                Uncategorized

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