Involvement of cellular senescence due to insufficient autophagy in the asthmatic inflammation in elderly.

<bold>Background:</bold> In recent years, asthma in the elderly has increased along with longer life expectancy. Older asthmatics experience worse airflow obstruction, more complications, and increased Th1 and Th17 inflammation. Previously, we have reported that in an ageing-related lung disease such as IPF or COPD, cellular senescence associated with insufficient autophagy is involved in pathogenesis via the senescence-associated secretary phenotype (SASP). <bold>Aims and objectives:</bold> To elucidate the involvement of insufficient autophagic response and associated cellular senescence in asthmatic inflammation in elderly. <bold>Methods:</bold> We conducted experiments using airway epithelial cells (HBECs) isolated from lung surgery specimens. Specifically, we compared the expression levels of p16, ATG5, IL-8, TSLP, and IL-33 in HBECs stimulated by house dust mites(HDM) at different passages (P3 and P7). <bold>Results:</bold> P16 levels increased in HBECs as passages advanced, especially with HDM stimulation. Additionally, ATG5 levels tended to be lower in P7HBECs than in P3HBECs, both at baseline and in response to HDM. While TSLP and IL-33 didn't consistently show significant differences, IL-8 expression was notably enhanced in P7HBECs and exhibited an HDM concentration-dependent pattern. <bold>Discussions and conclusions:</bold> These findings suggest allergenic triggers may accelerate cellular senescence in the elderly, potentially due to reduced autophagy activity. Enhanced cellular senescence induced by allergens could contribute to non-type 2 inflammation in older individuals, leading to refractory asthma. Ongoing investigations using both in vitro cell cultures and in vivo mouse models aim to directly explore this link.