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Research Article: Circadian disruption associated with nighttime light exposure contributes to airway epithelial remodeling via TIMELESS in childhood asthma

Date Published: 2026-04-23

Abstract:
Childhood asthma is a common inflammatory airway disease, and its occurrence is influenced by environmental factors. Artificial light at night (ALAN) can disrupt circadian rhythms, but its relationship with childhood asthma remains unclear. To evaluate the association between ALAN and childhood asthma, and to investigate the role of the circadian clock gene in this relationship. The study combined multiple approaches: an epidemiological analysis of asthma prevalence and urban ALAN levels in China; a pediatric asthma clinical study assessing nighttime light exposure, circadian disruption, and lung function; Mendelian randomization to test for a causal link between circadian disruption and asthma, and multi-omics plus experimental models to evaluate the function of TIMELESS , a circadian clock gene. ALAN exposure in Chinese cities has increased and was identified by AutoGluon modeling as a significant environmental risk factor for childhood asthma. In a pediatric asthma cohort, excessive nighttime light exposure was strongly associated with circadian rhythm disruption ( R =?0.756, p <?0.001). Mendelian randomization analysis supported a causal relationship between circadian rhythm disruption and asthma ( p =?0.040). Multi-omics analysis identified TIMELESS as a key circadian regulator that is highly expressed in the airway epithelium of asthmatic children. In an asthma mouse model, TIMELESS expression was upregulated in airway epithelium, and TIMELESS knockdown in airway epithelial cells significantly reduced their proliferation. Circadian disruption associated with nighttime light exposure may contribute to airway epithelial proliferation and remodeling via TIMELESS , potentially exacerbating childhood asthma.

Introduction:
Childhood asthma is a common inflammatory airway disease, and its occurrence is influenced by environmental factors. Artificial light at night (ALAN) can disrupt circadian rhythms, but its relationship with childhood asthma remains unclear. To evaluate the association between ALAN and childhood asthma, and to investigate the role of the circadian clock gene in this relationship.

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