Sex-Specific and Time-Varying Associations Between Cigarette Smoking and Telomere Length Among Older Adults

Abstract

Inconsistent associations between smoking and telomere length (TL) have been reported in epidemiologic studies, perhaps because of the time-varying nature of smoking behaviors. We estimated the associations of TL, which was measured by quantitative polymerase chain reaction using saliva DNA, with concurrent and past smoking status reported biennially for up to 16 years before TL measurement in 5,624 participants in the Health and Retirement Study (1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008). Smoking was associated with reduced TL when we used prospective data on smoking statuses among men and women, but the association was strongly attenuated among men in crosssectional analyses. This attenuation was largely due to a higher rate of smoking cessation during the study period among men with shorter TL than among men with longer TL. Short TL was also associated with poorer overall health in men, which suggests that male smokers with short TL were more likely to quit smoking because of poor health. Analyses of years since cessation, smoking duration, and pack-years of smoking all support the hypothesis that increased cigarette use shortens TL. Our results provide a potential explanation for the inconsistent associations between smoking and TL reported in previous cross-sectional studies. Time-varying associations should be considered in future studies of smoking behavior, TL, aging, and disease risk.aging; Health and Retirement Study; sex; smoking; smoking cessation; telomere length Abbreviations: HRS, Health and Retirement Study; TL, telomere length.Telomeres are DNA-protein complexes at chromosome ends that protect DNA from damage. Shortening of the DNA component of telomeres occurs with cell division, with average leukocyte telomere length (TL) decreasing by approximately 25 to 50 base pairs per year in adults (1). TL has been studied extensively as a biomarker of aging and susceptibility to age-related diseases, including cardiovascular diseases, cancers, and neurocognitive diseases (2-5).Cigarette smoking results in exposure to free radicals and reactive oxygen species, which leads to increased oxidative stress and inflammation (6). Both processes have also been linked to TL shortening (7-9), leading to the hypothesis that smoking promotes TL shortening (10). However, epidemiologic reports of smoking and TL have been inconsistent; in some studies, investigators reported shorter TL associated with smoking (11-20), whereas others found no association (21)(22)(23)(24)(25)(26). This inconsistency has also been seen in studies of smoking and longitudinal measures of TL attrition, with associations between smoking and TL shortening seen in some studies (17, 18) but not in others (19,20). Furthermore, a study of older men in Finland (27) found that smoking during midlife was associated with short TL measured later in life but that smoking was not associated with TL in crosssectional analyses conducted in later life, which suggests that the timing of smoking beh...

Suppression effect of body weight on the association between cigarette smoking and telomere length: the Bogalusa Heart Study

“…Our findings suggest that BMI modifies the association between cigarette smoking and LTL by suppressing the effect of smoking, which potentially contributes to the mixed findings reported on the smoking-LTL association in previous studies [13]. Other causes for the inconsistent findings might be suboptimal LTL measurements, small sample size, age range, sex, race, statistical analysis models and the number of covariates included, and often their complex interactions [4–7, 19–21].…”

Cigarette smoking and telomere length: A systematic review of 84 studies and meta-analysis

“…Furthermore, all studies included in the meta-analysis assessed circulating telomere length in blood. We were unable to assess any potential effect modification by sample source of telomere length such as saliva, which has also been linked to smoking ( Zhang et al, 2016 ). Leukocyte telomere length has been widely used as a representative parameter of individual telomere status and that shorter leukocyte telomere length has been linked with increased mortality in several studies ( Kimura et al, 2008 , Needham et al, 2015 ).…”

The association of sarcopenia, telomere length, and mortality: data from the NHANES 1999–2002

“…Sarcopenia has been defined as the loss of muscle mass and/or strength with aging 1 . The aging process can be affected by many epigenetic factors including smoking, air pollution, and diet 2 – 4 . Partly due to the impaired muscle enzymatic system that degrades reactive oxygen species, there is an increased exposure to these toxic entities that develops with aging that may hasten the development of sarcopenia 5 .…”