Telomere biology in early life and its environmental determinants

Abstract

Aging is a complex physiological process responsive to the genetic background and environmental factors operative during the life course of an individual. Attrition of telomeres (the ends of our chromosomes) is considered a primary hallmark of aging and extensive research on the determinants of telomere length in adults has been performed. Telomere length shortens with each cell division and accumulating DNA damaging effects caused by oxidative stress and inflammation during life contribute to a more rapid decline in telomere length. This may explain differences in aging rates between individuals. Telomere length may predict lifespan and susceptibility of developing age-related diseases, and is considered as a marker of biological aging. At birth, telomere length is highly variable due to differences in genetics and environmental exposures that occur during embryonic and fetal development. It has been hypothesized that the origins of health and disease in later life may be determined early in life or even during the prenatal life. Therefore, the programming of telomere biology at birth and during early life may be an important biological pathway underlying the developmental origins of later life health and disease. Knowledge on factors that determine telomere length at birth is scarce. In this thesis, we evaluated four different factors operative during the in utero life that may relate to the early biological aging process, by studying their relationship with newborn telomere length (as measured in cord blood and placental tissue). This dissertation consists of four main chapters. In the first two chapters, lifestyle- and behavioral factors were associated with newborn telomere length. We evaluated - in chapter one - to what extent maternal pre-pregnancy BMI and - in chapter two - parental socio-economic features relate to the aging process. We further evaluated two unavoidable environmental exposures, including prenatal ambient particulate matter air pollution - chapter three - and ambient temperature exposures - chapter four - in relation with newborn telomere length. In summary, we found that shorter newborn telomere length is associated with higher pre-pregnancy BMI, low socio-economic status, higher prenatal particulate matter and ambient temperature exposures (heat). Lower prenatal exposure to ambient temperature (cold) showed potential protective effects reflected by longer newborn telomere length. We observed that our findings were mostly consistent in the two evaluated newborn tissues (cord blood and placenta). Our results show that maintaining a healthy weight during the reproductive life may increase overall molecular longevity of the offspring. In addition, we show that, even in an affluent country such as Belgium, socio-economic differences still relate to differences in potential lifespans, as reflected by telomere length at birth. These results show the need for targeting and addressing direct determinants of socio-economic inequalities, which may increase public health from birth onwards. Additionally, we showed that air pollution exposures below the European Union accepted limit values clearly impact the molecular aging process. Besides, we showed for the first time that ambient temperature is associated with the aging process, reflected by telomere length, which may have severe consequences with respect to the global climate change. These results provide evidence for the need of simple but adequate human interventions and governmental actions to reduce global air pollution levels and arrest the further global warming process. These interventions may greatly impact global health across the different phases of life, which, as shown by our results, may start from life in the womb.