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Tetrabromobisphenol A (TBBPA) is one of the most prevalently used brominated flame retardants. Due to its persistence, it is predominantly found in environmental matrices and has the potential to generate multi-generational toxicity. However, knowledge of its adaptive response or long-term residual effect in multi-generations, and molecular mechanisms remain understudied. In the current study, the model animal nematode Caenorhabditis elegans (C. elegans) was exposed to TBBPA at environmentally realistic concentrations (0.1–1000 μg L−1) for four consecutive generations (G 0 to G 3). Degenerative age-related multiple endpoints including lifespan, locomotion behaviors, growth, reproduction, oxidative stress-related biochemical responses, cell apoptosis, and stress related gene expressions were assessed in the continuous exposure generations (G 0 and G 3) and the discontinuously exposed generations (T 3 and T′ 3). The results showed that changes in degenerative age-related response monitored four generations varied in direction and magnitude depending on the TBBPA concentrations, and the response intensify ranked as G 0 > T′ 3 /G 3 > T 3. TBBPA at 1 μg L−1 dosage was detected as the lowest observed effect concentration in multi-biomarkers. The underlying mechanism of aging phenotypes was that reactive oxygen species accumulation led to cell apoptosis regulated by gene ape-1 , and confirmed catalase enzyme and superoxide dismutase activity played a crucial role in the detoxification process of TBBPA at the molecular level. This study provided insights into the underlying mechanism of TBBPA-interfered longevity and its environmental multi-generational potential risks. [Display omitted] • TBBPA interfered lifespan of C. elegans over generations. • Lifespan was regulated by the transcription of apoptosis and aging-related genes. • Maternal generations exposure could have irreversible effects on the progeny. • Ape-1 regulated cell apoptosis and ultimately impacted longevity. [ABSTRACT FROM AUTHOR]

• In an exposure and rest model, PM2.5 paradoxically alleviated the disease severity and airway inflammatory responses in COPD-like mice. • PM2.5 and polycyclic aromatic hydrocarbons (PAHs) in PM2.5 induced inhibitory memory alveolar macrophages (AMs). • The induction of inhibitory trained AMs by PM2.5 was dependent on the IL-33 production from epithelial cells through the AhR/ARNT pathway. Fine particulate matter (PM2.5) concentrations have decreased in the past decade. The adverse effects of acute PM2.5 exposure on respiratory diseases have been well recognized. To explore the long-term effects of PM2.5 exposure on chronic obstructive pulmonary disease (COPD), mice were exposed to PM2.5 for 7 days and rest for 21 days, followed by challenges with lipopolysaccharide (LPS) and porcine pancreatic elastase (PPE). Unexpectedly, PM2.5 exposure and rest alleviated the disease severity and airway inflammatory responses in COPD-like mice. Although acute PM2.5 exposure increased airway inflammation, rest for 21 days reversed the airway inflammatory responses, which was associated with the induction of inhibitory memory alveolar macrophages (AMs). Similarly, polycyclic aromatic hydrocarbons (PAHs) in PM2.5 exposure and rest decreased pulmonary inflammation, accompanied by inhibitory memory AMs. Once AMs were depleted, pulmonary inflammation was aggravated. PAHs in PM2.5 promoted the secretion of IL-33 from airway epithelial cells via the aryl hydrocarbon receptor (AhR)/ARNT pathway. High-throughput mRNA sequencing revealed that PM2.5 exposure and rest drastically changed the mRNA profiles in AMs, which was largely rescued in IL-33−/− mice. Collectively, our results indicate that PM2.5 may mitigate pulmonary inflammation, which is mediated by inhibitory trained AMs via IL-33 production from epithelial cells through the AhR/ARNT pathway. We provide the rationale that PM2.5 plays complicated roles in respiratory disease. [ABSTRACT FROM AUTHOR]