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Updated: Apr 9, 2026

Techniques to Induce and Quantify Cellular Senescence
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Published on: May 1, 2017

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Dual role of MIF in aging and cellular senescence

Abdullah Altulea1, Jamil Nehme1, Marco Demaria1

  • 1European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), University of Groningen (RUG), Groningen, the Netherlands.

Cytokine & Growth Factor Reviews
|April 7, 2026
PubMed

Insights

Macrophage migration inhibitory factor (MIF) is a key cytokine in immunity and aging. Its dual roles in inflammation and cell survival present a complex therapeutic target for age-related diseases.

Area of Science:

  • Immunology
  • Cellular Biology
  • Pathology

Background:

  • Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine involved in innate immunity, cellular senescence, and age-related diseases.
  • MIF exhibits unique secretion mechanisms, compartment-specific signaling, and redox-dependent conformational states.

Purpose of the Study:

  • To review the multifaceted roles of MIF in various biological contexts and age-related pathologies.
  • To elucidate the distinct functions of extracellular and intracellular MIF.
  • To highlight oxidized MIF as a potential biomarker in aging.

Main Methods:

  • Systematic review of evidence from cardiovascular, neurodegenerative, musculoskeletal, and pulmonary disease studies.
  • Analysis of MIF's signaling pathways, including CD74, CXCR2/4, NF-κB, and p53 interactions.
  • Examination of MIF's redox-dependent conformational states.

Main Results:

  • Extracellular MIF promotes chronic inflammation via CD74, CXCR2/4, and NF-κB.
  • Intracellular MIF supports proliferation, DNA repair, and autophagy by antagonizing p53.
  • Oxidized MIF is identified as a relevant marker in age-related diseases.
  • MIF signaling demonstrates context-dependent protective or deleterious effects across different diseases.

Conclusions:

  • MIF's complex and context-dependent functions make it a challenging therapeutic target for age-related diseases.
  • Understanding MIF's distinct signaling pathways and conformational states is crucial for therapeutic development.
Keywords:
AgingInflammationMIFSenescence

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