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      Maternal pre-pregnancy body mass index and newborn telomere length

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          Abstract

          Background

          Newborn telomere length sets telomere length for later life. At birth, telomere length is highly variable among newborns and the environmental factors during in utero life for this observation remain largely unidentified. Obesity during pregnancy might reflect an adverse nutritional status affecting pregnancy and offspring outcomes, but the association of maternal pre-pregnancy body mass index (BMI) with newborn telomere length, as a mechanism of maternal obesity, on the next generation has not been addressed.

          Methods

          Average relative telomere lengths were measured in cord blood ( n = 743) and placental tissue ( n = 702) samples using a quantitative real-time PCR method from newborns from the ENVIR ONAGE birth cohort in Belgium. By using univariate and multivariable adjusted linear regression models we addressed the associations between pre-pregnancy BMI and cord blood and placental telomere lengths.

          Results

          Maternal age was 29.1 years (range, 17–44) and mean (SD) pre-pregnancy BMI was 24.1 (4.1) kg/m 2. Decline in newborn telomere length occurred in parallel with higher maternal pre-pregnancy BMI. Independent of maternal and paternal age at birth, maternal education, gestational age, newborn gender, ethnicity, birthweight, maternal smoking status, parity, cesarean section, and pregnancy complications, each kg/m 2 increase in pre-pregnancy BMI was associated with a −0.50 % (95 % CI, −0.83 to −0.17 %; P = 0.003) shorter cord blood telomere length and a −0.66 % (95 % CI, −1.06 to −0.25 %; P = 0.002) shorter placental telomere length.

          Conclusions

          Maternal pre-pregnancy BMI is associated with shorter newborn telomere lengths as reflected by cord blood and placental telomeres. These findings support the benefits of a pre-pregnancy healthy weight for promoting molecular longevity from early life onwards.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12916-016-0689-0) contains supplementary material, which is available to authorized users.

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          Most cited references49

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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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            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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              A crucial role for adipose tissue p53 in the regulation of insulin resistance.

              Various stimuli, such as telomere dysfunction and oxidative stress, can induce irreversible cell growth arrest, which is termed 'cellular senescence'. This response is controlled by tumor suppressor proteins such as p53 and pRb. There is also evidence that senescent cells promote changes related to aging or age-related diseases. Here we show that p53 expression in adipose tissue is crucially involved in the development of insulin resistance, which underlies age-related cardiovascular and metabolic disorders. We found that excessive calorie intake led to the accumulation of oxidative stress in the adipose tissue of mice with type 2 diabetes-like disease and promoted senescence-like changes, such as increased activity of senescence-associated beta-galactosidase, increased expression of p53 and increased production of proinflammatory cytokines. Inhibition of p53 activity in adipose tissue markedly ameliorated these senescence-like changes, decreased the expression of proinflammatory cytokines and improved insulin resistance in mice with type 2 diabetes-like disease. Conversely, upregulation of p53 in adipose tissue caused an inflammatory response that led to insulin resistance. Adipose tissue from individuals with diabetes also showed senescence-like features. Our results show a previously unappreciated role of adipose tissue p53 expression in the regulation of insulin resistance and suggest that cellular aging signals in adipose tissue could be a new target for the treatment of diabetes (pages 996-967).
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                Author and article information

                Contributors
                dries.martens@uhasselt.be
                michelle.plusquin@uhasselt.be
                wilfired.gyselaers@zol.be
                nhidv@channing.harvard.edu
                tim.nawrot@uhasselt.be
                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central (London )
                1741-7015
                18 October 2016
                18 October 2016
                2016
                : 14
                : 148
                Affiliations
                [1 ]Centre for Environmental Sciences, Hasselt University, Hasselt, 3500 Belgium
                [2 ]MRC/PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, W2 1PG UK
                [3 ]Department of Obstetrics, East-Limburg Hospital, Genk, 3600 Belgium
                [4 ]Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02215 USA
                [5 ]Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, MA 02115 USA
                [6 ]Department of Public Health & Primary Care, Leuven University, Leuven, 3000 Belgium
                Article
                689
                10.1186/s12916-016-0689-0
                5067896
                27751173
                24fdf97e-122d-4b60-aae9-25639f6a525f
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 24 June 2016
                : 8 September 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000781, European Research Council;
                Award ID: ERC-2012-StG 310898
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2016

                Medicine
                telomeres,newborns,pre-pregnancy body-mass index,in utero life
                Medicine
                telomeres, newborns, pre-pregnancy body-mass index, in utero life

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