Study links early-life tobacco exposure to accelerated aging, urging preventive action

By Priyanjana Pramanik, MSc.Reviewed by Susha Cheriyedath, M.Sc.May 6 2024

In a recent study published in the journal Science Advances, researchers investigated the impact of early-life tobacco exposure on aging-related diseases. They found that in-utero tobacco exposure is associated with increases in the rate of biological aging.

Their findings indicate that reducing early-life tobacco exposure is crucial for improving healthy aging, as it significantly influences biological aging and interacts with various factors such as age, sex, deprivation, and diet.

Study: Early-life exposure to tobacco, genetic susceptibility, and accelerated biological aging in adulthood. Image Credit: New Africa / Shutterstock

Background

Biological aging is a complex process characterized by cumulative cellular changes that progressively deteriorate tissue and organ integrity. This leads to increased vulnerability to morbidity and mortality and imposes a substantial financial burden on healthcare systems.

Recent reviews have underscored the importance of quantifying biological age (BA) through various biomarkers to predict health outcomes accurately. Early-life environmental exposures, particularly tobacco exposure, have been identified as significant risk factors for adverse health outcomes in adulthood.

While previous research has linked tobacco exposure to accelerated aging in early life, its effects on adult biological aging remain unclear, especially regarding the timing of exposure and genetic susceptibility.

About the study

This study examined the association between early-life exposure to tobacco and adult biological aging using multiple biomarkers, including telomere length (TL) and composite clinical-parameter algorithms.

Additionally, it investigated the combined impact of genetic susceptibility and tobacco exposure on acceleration in biological aging, aiming to provide insights for preventive and therapeutic interventions targeting healthy aging.

The study utilized data from the UK Biobank, a population-based cohort study comprising approximately half a million participants aged 37 to 73 years enrolled between 2006 and 2010. After exclusions, a total of 276,259 participants were included.

Early-life tobacco exposure, encompassing in-utero exposure and age of smoking initiation, was assessed via self-reported questionnaires. BA was determined using Klemera-Doubal Biological Age (KDM-BA) and phenotypic age (PhenoAge) algorithms validated with NHANES data.

TL in leukocytes was measured using a quantitative polymerase chain reaction. Polygenic risk scores (PRS) were constructed using genetic variants associated with aging phenotypes and TL.

Covariates included demographic and lifestyle factors. Statistical analyses involved linear regression models adjusted for covariates to estimate associations between tobacco exposure, PRS, and biological aging indicators.

Sensitivity analyses were conducted to assess robustness, including adjustments for additional confounders and stratified analyses by demographic and lifestyle factors.

Findings

Initial participant comparisons indicated that individuals with in-utero exposure tended to be marginally younger, predominantly male, and more inclined towards alcohol consumption. Moreover, they exhibited elevated metrics such as body mass index (BMI) and Townsend deprivation index (TDI), along with a higher prevalence of major diseases.

Further statistical analysis revealed robust associations between early-life tobacco exposure and accelerated biological aging.

Notably, subjects with in-utero exposure demonstrated significant increments in both KDM-BA and PhenoAge acceleration, coupled with a noteworthy TL reduction. Specifically, in-utero exposure was linked with a 0.26-year increase in KDM-BA acceleration, a 0.49-year increase in PhenoAge acceleration, and a 5.34% decrease in TL.

Furthermore, a clear dose-response trend emerged regarding the smoking initiation age, with earlier commencements correlating with a more pronounced acceleration in biological aging markers.

For instance, childhood tobacco exposure was associated with a 0.88-year increase in KDM-BA acceleration, a 2.51-year increase in PhenoAge acceleration, and a 10.53% decrease in TL, compared to never-smokers.

Exploration into the combined effects of genetic predisposition and early-life tobacco exposure underscored substantial impacts on accelerated aging.

Those with heightened PRS and either in-utero exposure or early smoking initiation exhibited the most pronounced acceleration in biological aging markers.

Stratified analyses further illuminated nuanced interactions between early-life tobacco exposure and demographic or lifestyle factors.

For instance, younger participants subjected to in-utero exposure showcased heightened acceleration in biological aging markers, while the effects were amplified in individuals residing in areas of high deprivation.

Conclusions

This study investigates how early-life tobacco exposure, encompassing fetal, childhood, and adolescent periods, relates to higher rates of biological aging during adulthood.

In a large-scale analysis, in-utero tobacco exposure and smoking initiation age notably correlate with accelerated aging markers and shortened telomere length.

The findings from this study underscore the multifaceted interplay between exposure to tobacco in early life, genetic predisposition, and environmental factors in shaping the trajectory of biological aging.

Limitations include retrospective self-reporting and potential confounding factors, but sensitivity analyses support the robustness of the results. Further research is needed to understand the underlying mechanistic pathways and include more diverse cohorts to validate these findings.