Sepsis continues to pose a significant threat to human life and represents a substantial financial burden. In addition to replicative stress resulting from telomeric loss, recent studies have identified multiple factors contributing to cell cycle arrest. Furthermore, our understanding of pathways associated with cellular senescence, such as CD47-mediated suppression of efferocytosis, has expanded. However, beyond in vitro experiments, the impact of cell stress during complex systemic illnesses, including sepsis, remains poorly understood. Consequently, we conducted an investigation into molecular alterations related to senescence-associated pulmonary mechanisms during experimental nonpulmonary sepsis.

Our findings suggest an activation of senescent-associated pathways during experimental sepsis. However, expanding the experiments to other organ systems and in vivo long-term models are necessary to further evaluate the sustained mechanisms and immunopathophysiological consequences of cellular senescence triggered by septic organ injury.

Male C57BL/6JRj mice were anesthetized and subjected to either control conditions (sham) or cecal ligation and puncture (CLP) to induce sepsis. Twenty-four hours or 7 d after CLP, animals were killed, and blood, bronchoalveolar fluids, and lungs were harvested and analyzed for morphological and biochemical changes.

Histological damage in pulmonary tissue, as well as increases in plasma levels of surfactant protein D, indicated development of alveolar-focused acute lung injury after CLP. Additionally, we observed a significant upregulation of the CD47-QPCTL-SHP-1 axis in lungs of septic mice. Whereas the expression of p16, a marker primarily indicating manifested forms of senescence, was decreased after CLP, the early marker of cellular senescence, p21, was increased in the lungs during sepsis. Later, at 7 d after CLP, pulmonary expression of CD47 and QPCTL-1 was decreased, whereas SHP-1 was significantly enhanced.