Effect of Earlier Age of Tobacco Exposure on Accelerated Biological Aging in Adulthood

OBJECTIVE: To investigate how early-life tobacco exposures implicate accelerated biological aging in adulthood and the potential mechanism. PARTICIPANTS AND METHODS: This study used questionnaires to determine when the participants smoked and whether their mothers smoked when pregnant. Early-life tobacco exposures included in utero tobacco exposure and age of smoking initiation. For evaluating biological aging, we used the following 8 outcome measures: telomere length, frailty index, homeostatic dysregulation score, Klemera-Doubal method biological age, age-related hospitalization rate, premature death, and life expectancy. Mediation analysis was used to identify the role of inflammation factors. RESULTS: During a median follow-up of 14.6 years, 8 outcome measures in participants were analyzed for age of smoking initiation (N=320,453). Compared with never smoking, smoking initiation at age 5 to 12 years (β=3.043; 95% CI, 2.683 to 3.403 and β=-0.011; 95% CI, -0.016 to -0.006), 13 to 17 years (β=1.343; 95% CI, 1.226 to 1.460 and β=-0.007; 95% CI, -0.009 to -0.005), and 18 years and above (β=0.949; 95% CI, 0.823 to 1.075 and β=-0.004; 95% CI, -0.006 to -0.003) were significantly associated with increased Klemera-Doubal method bioage and shorter telomere length, as well as with other aging-related outcome measures. Markers of inflammation significantly mediated up to 0.00% to 43.58% of the studied associations above. CONCLUSION: In utero tobacco exposure and earlier age of smoking initiation were significantly associated with accelerated biological aging. These associations were in part mediated through inflammation markers.