The Hallmarks of Environmental Insults and early childhood development

Abstract

BACKGROUND AND AIM: Aging is a complex physiological phenomenon. The question why some subjects grow old while remaining free from disease whereas others prematurely die remains largely unanswered. We focus here on the role of air pollution and other environmental factors in biological aging from early life onwards. METHODS: Some of the hallmarks of aging are overlapping with the hallmarks of environmental insults including three main categories: genomic instability, telomere attrition, and epigenetic alterations leading to altered mitochondrial function and cellular senescence. RESULTS:During in-utero development, the fetus is susceptible to transplacental exposure to carcinogenic air particles. We proved translocation of black carbon from mother to fetus. Even below European Union air pollution thresholds, exposure to particulate matter is associated with an increased placental mutation rate. This increased mutation rate occurred in concert with epigenetic alterations in key DNA repair and tumor suppressor genes in the placenta. Moreover, at birth, the initial telomere length of the newborn is largely determined by environmental factors including prenatal air pollution, green space exposure, pre-pregnancy BMI as well as by maternal socio-economic factors. Telomere length at birth is a major predictor of later life telomere length and predicts telomere change in the transition from birth to child- and adulthood. Therefore, telomere length related health and disease later in life may be programmed at birth. Understanding the setting of initial telomere length and its environmental determinants may further gain insights in the developmental origins of health and disease. CONCLUSIONS:The telomere length – mitochondrial axis is a hallmark of environmental insults during gestation. Improved air quality may promote molecular longevity from birth onward. KEYWORDS: Ageing, telomeres, mitochondria, exposome, DOHaD