Smoking does not accelerate leucocyte telomere attrition: a meta-analysis of 18 longitudinal cohorts

Abstract

Smoking is associated with shorter leucocyte telomere length (LTL), a biomarker of increased morbidity and reduced longevity. This association is widely interpreted as evidence that smoking causes accelerated LTL attrition in adulthood, but the evidence for this is inconsistent. We analysed the association between smoking and LTL dynamics in 18 longitudinal cohorts. The dataset included data from 12 579 adults (4678 current smokers and 7901 non-smokers) over a mean follow-up interval of 8.6 years. Meta-analysis confirmed a cross-sectional difference in LTL between smokers and non-smokers, with mean LTL 84.61 bp shorter in smokers (95% CI: 22.62 to 146.61). However, LTL attrition was only 0.51 bp yr −1 faster in smokers than in non-smokers (95% CI: −2.09 to 1.08), a difference that equates to only 1.32% of the estimated age-related loss of 38.33 bp yr −1 . Assuming a linear effect of smoking, 167 years of smoking would be required to generate the observed cross-sectional difference in LTL. Therefore, the difference in LTL between smokers and non-smokers is extremely unlikely to be explained by a linear, causal effect of smoking. Selective adoption, whereby individuals with short telomeres are more likely to start smoking, needs to be considered as a more plausible explanation for the observed pattern of telomere dynamics.

Age-Dependent Assessment of Genes Involved in Cellular Senescence, Telomere, and Mitochondrial Pathways in Human Lung Tissue of Smokers, COPD, and IPF: Associations With SARS-CoV-2 COVID-19 ACE2-TMPRSS2-Furin-DPP4 Axis

“…Several DNA damaging agents present in smoke, which may activate the DNA damage response, thereby influencing telomere function leading to accumulation of senesced cells. However, recent meta-analysis suggests that even though smokers are associated with shorter telomere length, the study implicates that smoking does not accelerate the telomere attrition in leucocytes (Bateson et al, 2019).…”

Controlling for baseline telomere length biases estimates of the rate of telomere attrition

“…It is worth pointing out that scenario B is unlikely to be very common, unless LTL b is measured early in life, before the participants have started smoking. Likewise, scenario A is not typical, given the abundant cross-sectional evidence that smokers have shorter telomeres than non-smokers [2,3]. Thus, the scenarios likely to be empirically widespread are exactly those (C and D) where bias will occur if LTL b is controlled for.…”

“…Given first, that there are robust differences in LTL b between smokers and non-smokers [2,3], second, that LTL measurement error is often substantial ([34] and figure 5) and third, that most published analyses of the effect of smoking on ΔLTL or LTL fu control for LTL b , we suggest that the difference in ΔLTL between smokers and non-smokers is likely to have been overestimated in the literature. Reports of significantly accelerated LTL attrition in smokers compared to non-smokers should therefore be interpreted with caution (e.g.…”

“…Many cross-sectional studies of LTL demonstrate that mean LTL is shorter in individuals that have been exposed to diverse forms of adversity [1]. Recent meta-analyses show that LTL tends to be shorter in individuals who are smokers [2,3], are more sedentary [4,5], are obese [6], were subjected to childhood trauma [7] or psycho-social stress [8], suffer from schizophrenia [9,10], post-traumatic stress disorder [11], anxiety or depression [12,13] or have higher perceived stress [14]. These studies have been widely assumed to support the hypothesis that the exposure increases the rate of LTL attrition.…”

“…In the case of LTL, two meta-analyses have confirmed that smokers have shorter LTL than non-smokers in cross-sectional datasets [2,3]. Thus, longitudinal datasets are likely to show a baseline association between smoking and LTL.…”