Dual role of MIF in aging and cellular senescence

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that bridges innate immunity, cellular senescence and age‑related pathology. In this review, we describe the unique secretion mechanisms, compartment‑specific signaling, and redox‑dependent conformational states that MIF has in different contexts. We detail how extracellular MIF amplifies chronic inflammation through CD74, CXCR2/4 and NF‑κB, while intracellular MIF sustains proliferation, DNA repair, and autophagy by antagonizing p53. We also highlight oxidized MIF as an emerging marker with unique relevance in age-related diseases. Through systematic comparison of evidence from cardiovascular, neurodegenerative, musculoskeletal and pulmonary disease studies, this review reveals context‑dependent protective versus deleterious outcomes of MIF signaling. The nature of MIF and its involvement in age-related diseases makes it a challenging yet intriguing therapeutic target.