Service Communautaire d'Information sur la Recherche et le Développement - CORDIS

FP7

ENVIRONAGE Report Summary

Project reference: 310898
Funded under: FP7-IDEAS-ERC

Mid-Term Report Summary - ENVIRONAGE (Unravelling environmental exposures in the core axis of ageing)

Although universal and unavoidable, ageing does not occur in a uniform way. AGEing is a complex phenotype, responsive to a plethora of ENVIRONmental inputs (ENVIRONAGE). Age related conditions in adults (cardiovascular, neurological ageing) often find their origin in risk factors operative in early life. Relevant exposures are likely to include maternal nutrition and air pollution. The molecular mechanisms behind these phenomena remain largely unknown. Mitochondria are involved in a variety of critical cell functions, including oxidative energy production and programmed cell death. The mitochondrial DNA function which have been shown to change under different energy demands, as well as different physiological conditions such as ageing. Telomeres, the distal ends of chromosomes, protect chromosomes from structural degradation, inappropriate recombination and also end-to-end fusion. Telomere length is highly heritable and erosion leads to an increasingly vulnerable structural integrity of the chromosomes. It is considered a marker of overall biological age compared with chronological age. For now, findings from the ENVIRONAGE birth cohort limit to the first phase of the study (birth) since the follow-up phase is still ongoing. We have shown that air pollution exposure during pregnancy induces molecular, cellular, and hormonal changes in placental tissue and cord blood, which are representative tissues for the fetus. The placenta is considered the main target organ since it serves as the gatekeeper between mother and fetus for all nutritional, hormonal, and other environmental stress factors throughout pregnancy. Important findings on telomere biology early in life showed influence by maternal BMI, traffic related air pollution and residential greenness. First, we provide evidence for an association between maternal pre-pregnancy BMI and telomere lengths of newborns in both cord blood and placental tissue. The key finding is that maternal pre-pregnancy BMI is associated with shorter newborn cord blood and placental telomeres. Our finding shed light of pre-pregnancy effects of mothers BMI on the next generation. Indeed, our data showed that for each BMI point increase average relative cord blood telomeres were 0·50% shorter and average relative placental telomeres were 0·66% shorter. The telomere loss in newborns of obese mothers may increase the risk for chronic diseases in adulthood. Based on longitudinal studies an annual loss between 32.2 and 45.5 bp is estimated in adult leukocytes, indicating that each maternal pre-pregnancy BMI point increase is equivalent to a loss of 1.1 to 1.6 telomere year equivalence in adulthood. This illustrates the public health significance of our findings as newborns from obese mothers compared with newborns from normal weight mothers were biologically about 10 years older, based on telomeric year equivalence in adulthood. Furthermore, we found that maternal residential proximity to a major road was associated with placental telomere length: a doubling in the distance to the nearest major road was associated with a 5.32% (95% CI: 1.90 to 8.86%; p=0.003) longer placental telomere length at birth. In addition, an interquartile increase (22%) in maternal residential surrounding greenness (5 km buffer) was associated with an increase of 3.62% (95% CI: 0.20 to 7.15%; p=0.04) in placental telomere length. We showed that maternal residential proximity to traffic and lower residential surrounding greenness is associated with shorter placental telomere length at birth. This may explain a significant proportion of air pollution-related adverse health outcomes starting from early life, since shortened telomeres accelerate the progression of many diseases. At the epigenetic level we found air pollution induced alterations in placental tissue on global methylation, specific methylation of genes involved in neurcognition as well as miRNA involved in telomere biology. Our results support the ENVIRONAGE hypothesis, i.e. that environmental inputs influence biomolecular markers of ageing including mitochondrial function, telomere length along with DNA repair and epigenetics as the ‘core axis of ageing’.

Contact

Nivelle, Nele (Research coordination officer)
Tel.: +32 11 268342
Fax: +32 11 268324
E-mail
Record Number: 183525 / Last updated on: 2016-06-16
Information source: SESAM