Shift work, accelerated biological aging and mortality risk in US adults: a national prospective cohort study.

OBJECTIVE: To examine the association between shift work and all-cause and cause-specific mortality in the U.S. population and assess whether biological age acceleration mediates this relationship. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study included 7548 adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2010, with mortality follow-up through 2019. EXPOSURE: Shift work included regular night, evening, or rotating shifts versus daytime schedules. MAIN OUTCOMES AND MEASURES: Primary outcomes were all-cause, cardiovascular (CVD), and cancer mortality. RESULTS: Among 7548 participants (mean follow-up 11.6 years), 358 deaths occurred. Shift work was associated with significantly increased all-cause mortality after full adjustment (HR = 1.52; 95% CI 1.09-2.13). CVD and cancer mortality associations were non-significant. No statistically significant interactions were observed in subgroup analyses of all-cause mortality. Shift workers showed greater PhenoAge acceleration (β = 0.39 years), which statistically accounted for 6.18% of the association between shift work and all-cause mortality. CONCLUSIONS AND RELEVANCE: Shift work was associated with higher all-cause mortality and greater PhenoAge acceleration. PhenoAge acceleration may statistically account for a small proportion of this association, although causal mediation cannot be inferred.