INMA: “Tobacco smoke exposure during pregnancy induces biological aging in childhood”
A study based on six European birth cohorts, including the INMA study, assesses the relation of prenatal and childhood exposure to tobacco smoke with telomere length and mitochondrial DNA content in children at the age of 8 years.
Prevalence of tobacco smoking in women is around 19% in Europe, and despite a decrease of maternal smoking during pregnancy, pregnant women are still exposed to second-hand tobacco smoke in public places. Cigarette smoke is known to contain toxic and carcinogenic compounds, and early life exposure has been associated with higher cardiovascular risk later in life, asthma, and reduced lung function. However, little is known about possible mechanisms and there is some evidence that oxidative stress is in the pathway between tobacco smoke exposure and health effects.
Telomere length and mitochondrial DNA content are biomarkers related to cellular aging, oxidative stress and inflammation, and may therefore be of interest. Telomeres are non-coding DNA sequences at the end of chromosomes that protect coding DNA against erosion, genomic instability and end-to-end fusions. Telomere length shortens with each cell division and is considered a biomarker of cellular aging. Shorter telomeres have been associated with age-related diseases such as cardiovascular disease, and type 2 diabetes. Telomeric DNA are highly sensitive to reactive oxygen damage. On the other hand, DNA mitochondria, which is inherited from the maternal line, is also vulnerable to oxidative damage. Mitochondria are the cellular organelles that produce the energy necessary for the cell’s survival and functioning.
Environmental factors might have higher impact on telomere length in early life than in adulthood because telomere length is mainly determined at birth and it declines at a higher rate in childhood than in adulthood. Similarly, mitochondrial function is essential for developmental processes.
Questionnaires and assessment of cotinine levels in urine were used to classify women as not exposed to smoking (<10 mg/L), exposed to secondhand smoke (10–50 mg/L) and active smokers (>50 mg/L). Cotinine is a substance produced by the body after being exposed to nicotine, and therefore can be used to estimate the exposition to tobacco. When the children were around 8 years of age, the same protocol was used to assess their tobacco smoke exposure. Telomere length and mitochondrial DNA content were measured in leukocytes (white blood cells) (in the case mitochondrial DNA, it was measured in buffy coats, which also includes platelets), in the children at 8 years, and employing real time polymerase chain reaction (qPCR). The effect of tobacco smoke exposure on the mentioned biomarkers was estimated using statistical models correcting by the potential effect of other sociodemographic and lifestyle factors that are known to influence them as well.
Maternal cotinine levels indicative of second-hand smoke exposure during pregnancy were associated with a decrease of 3.90% in leukocyte telomere length in children, compared with non- smoking, whereas the association for maternal cotinine levels indicative of active smoking (which was associated with a decrease of 3,24% in leukocyte telomere length) was not statistically significant. Childhood tobacco exposure was not associated with leukocyte telomere length, but global second-hand exposure during childhood was associated with an increase of 3.51% in mitochondrial DNA content.
Findings suggest that prenatal exposure to tobacco smoke, even at second-hand smoke levels, may accelerate telomere shortening in children and thus induce biological aging from an early age. Authors highlighted that results were more consistent amongst children of mothers with passive smoke exposure, and at prenatal period. Finally, the fact that results were consistent between children from the different cohorts included in the study, supports the robustness of the findings.
Reference: Osorio-Yáñez C, Clemente DBP, Maitre L, Vives-Usano M, Bustamante M, Martinez D, Casas M, Alexander J, Thomsen C, Chatzi L, Gützkow KB, Grazuleviciene R, Martens DS, Plusquin M, Slama R, McEachan RC, Wright J, Yang TC, Urquiza J, Tamayo I, Sunyer J, Vafeiadi M, Nawrot TS, Vrijheid M. Early life tobacco exposure and children’s telomere length: The HELIX project.Sci Total Environ. 2020 Apr 1;711:135028. doi: 10.1016/j.scitotenv.2019.135028. Epub 2019 Nov 20.