2. Academic Validation
  3. Identifying novel aging-related diagnostic and prognostic models and aging-targeted drugs for sepsis patients

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

  • Sci Rep. 2024 Dec 28;14(1):31445. doi: 10.1038/s41598-024-83111-1.
Kai Yang # 1 2 3,  Yaoyao Lu # 4,  Jian Gu 1 2 3,  Yingli Nie 5,  Tao Zhang 6 7 8
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2 Key Laboratory of Anesthesiology and Resuscitation, Ministry of Education, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 4 Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 5 Department of Dermatology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China. yingli_nie@163.com.
  • 6 Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 2019xh0150@hust.edu.cn.
  • 7 Key Laboratory of Anesthesiology and Resuscitation, Ministry of Education, Huazhong University of Science and Technology, Wuhan, China. 2019xh0150@hust.edu.cn.
  • 8 Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 2019xh0150@hust.edu.cn.
  • # Contributed equally.
PMID: 39732977 DOI: 10.1038/s41598-024-83111-1
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.

Keywords

Aging; Classification; Diagnosis; Prognosis; Sepsis; Thalidomide.

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