Identifying novel aging-related diagnostic and prognostic models and aging-targeted drugs for sepsis patients.

Abstract

Sepsis is defined as a dysfunctional, life-threatening response to infection leading to multiorgan dysfunction and failure. During the past decade, studies have highlighted the relationship between sepsis and aging. However, the role of aging-related mechanisms in the progression and prognosis of sepsis remains unclear. In the present study, we divided sepsis patients into High- and Low-aging groups based on the gene set variation analysis (GSVA) scores of GOBP-AGING gene set. Sepsis patients in the high-aging group exhibited higher levels of infiltration of innate immune cells, lower levels of infiltration of adaptive immune cells, and a worse prognosis than those in the Low-aging group. Additionally, the MPO to MME ratio (MPO/MME) appears to be an effective biomarker for predicting the prognosis of sepsis patients. Moreover, ARG1/SEC63 and ARG1/CDKN1C appear to be effective and robust biomarkers for the early diagnosis of sepsis patients. Finally, we found that thalidomide (TAL) significantly ameliorated LPS induced inflammation and organ injury and attenuated LPS induced cellular senescence in lung and kidney. Overall, this study provides new insights into the heterogeneity of sepsis, reveals the vital role of aging-related markers in the prognosis and diagnosis of sepsis and demonstrates that TAL is a novel aging-targeted drug for sepsis patients by attenuating LPS induced cellular senescence.