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FRIMEDBIO-Fri prosj.st. med.,helse,biol

The intrauterine redox state and telomere length in the newborn

Alternativ tittel: Risikofaktorer i livmoren og telomerelengde hos nyfødte

Tildelt: kr 9,8 mill.

Det har ikke vært noen endringer i forhold til det som var beskrevet før.

Recent studies infer causal roles for long telomeres in major human cancers and short telomeres in cardiovascular disease. They also suggest that longer telomeres in women than men might partially explain women's longer life expectancy. As telomere length (TL) is largely determined at birth, it is essential to understand factors that modify TL in the newborn. This project focuses on key intrinsic and extrinsic factors that are likely to affect TL dynamics in utero. Such intrauterine exposures include oxidative stress, which might increase telomere shortening with cell replication. This project will examine the (1) association between newborn's leukocyte TL (LTL) and mitochondrial genotypes, given that the mitochondria are a key intrinsic source of reactive oxygen species (ROS), and (2) associations between newborn's LTL and maternal smoking during pregnancy, given that tobacco smoke is a rich extrinsic source of ROS. The hypothesis that drives aims 1 and 2 is that the redox state during early gestation has a considerable impact on LTL dynamics in utero and therefore LTL at birth. To test this hypothesis, this project leverages ongoing research in the Norwegian MoBa study. Elucidating factors that make LTL short or long in newborns is not just scientifically interesting, it might also help guide the development of effective modalities for monitoring disease susceptibility, given that LTL at birth largely defines LTL throughout the life course. Innovation of this proposal stems from the novelty of the hypothesis which provides a whole new way of examining factors that influence TL. Moreover, the setting of MoBa, the availability of high quality DNA, and confluence of the investigators' expertise make this project unique. If results support our hypothesis, then this work will bring into focus the role of inherent and extrinsic factors within the intrauterine milieu in fashioning TL in the newborn and usher telomere epidemiology into a new era of mitochondrial genomics.

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FRIMEDBIO-Fri prosj.st. med.,helse,biol

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