2. Academic Validation
  3. Senescent cells promote viral infection-associated inflammation and tissue damage through a robust NF-κB pathway

Senescent cells promote viral infection-associated inflammation and tissue damage through a robust NF-κB pathway

  • Cell Commun Signal. 2025 Oct 28;23(1):464. doi: 10.1186/s12964-025-02466-8.
Mingfu Tian # 1 2,  June Ma # 3,  Zhiqiang Li # 1,  Chenglin Ye 1,  Xianghua Cui 1,  Guolei Wang 1,  Siyu Liu 2,  Muhammad Suhaib Qudus 2,  Uzair Afaq 2,  Hong Fan 1,  Jiali Xiong 4,  Guangli Li 5,  Chuanjin Luo 2,  Zhen Wang 6,  Zhengjiang Jin 3,  Ming Guo 2,  Xin Wang 2,  Zhixiang Huang 2,  Fang Zheng 7,  Kailang Wu 2,  Chengliang Zhu 8
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.
  • 2 State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, PR China.
  • 3 Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, PR China.
  • 4 Department of Emergency, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.
  • 5 Postgraduate Training Base at Shanghai Gongli Hospital, Ningxia Medical University, Shanghai, 200135, PR China.
  • 6 Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.
  • 7 Hubei Clinical Research Center for Molecular Diagnosis and Department of Clinical Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430000, PR China.
  • 8 Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China. [email protected].
  • # Contributed equally.
PMID: 41152908 DOI: 10.1186/s12964-025-02466-8
Abstract

Respiratory virus infections have been presenting significant global public health challenges. The virulence of SARS-CoV-2 and seasonal influenza largely relies on triggering abnormal host immune responses, particularly the production of a cytokine storm, which is notably increased in elderly patients. However, as the mechanisms underlying this age-associated exacerbation remain unclear, we investigated the role of the aging tissue microenvironment in promoting inflammation associated with viral Infection. Our research, based on clinical samples, cellular experiments, and mouse models, provides evidence that the aging lung microenvironment induces severe inflammatory responses and leads to tissue damage, with senescent cells playing a crucial role in this process. Further mechanistic insights reveal that elevated levels of downstream inflammatory factors result from a significant and robust activation of the NF-κB pathway. This increase is attributed to the accumulation of Reactive Oxygen Species in senescent cells and subsequent reduced expression of PDLIM2, an E3 ubiquitin Ligase regulating P65 degradation. Finally, restoring PDLIM2 significantly inhibits viral infection-mediated inflammatory responses and organ damage in the aging body. Therefore, this study offers a novel perspective by elucidating the molecular mechanism and exploring the therapeutic potential behind viral infection-related inflammatory responses, particularly the mechanism accelerating inflammatory storms in elderly patients post-infection.

Keywords

Inflammation; NF-κB; PDLIM2; Senescence; Virus.

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