Myeloid-derived suppressor cells (MDSC): an important partner in cellular/tissue senescence.

The aging process is associated with a low-grade chronic inflammation and the accumulation of senescent cells into tissues. Diverse stresses can trigger cellular senescence, a cell fate characterized by cell-cycle arrest and flat morphology. Oncogenic signaling can also induce cellular senescence which has been termed oncogene-induced senescence (OIS). Senescent cells display a pro-inflammatory phenotype which has been called the senescence-associated secretory phenotype (SASP). The secretomes associated with SASP contain colony-stimulating factors and chemokines which stimulate the generation of myeloid-derived suppressor cells (MDSC) by enhancing myelopoiesis in bone marrow and spleen. Enhanced myelopoiesis and increased level of MDSCs have been observed in bone marrow, spleen, and blood in both tumor-bearing and aged mice. Immunosuppressive MDSCs are recruited via chemotaxis into inflamed tissues where they proliferate and consequently suppress acute inflammatory reactions by inhibiting the functions of distinct components of innate and adaptive immunity. For instance, MDSCs stimulate the activity of immunosuppressive regulatory T-cells (Tregs). They also increase the expression of amino acid catabolizing enzymes and the secretion of anti-inflammatory cytokines, e.g. IL-10 and TGF-β, and reactive oxygen species (ROS). On the other hand, the accumulation of MDSCs into tissues exerts harmful effects in chronic pathological disorders, e.g. tumors and many age-related diseases, since the immunosuppression induced by MDSCs impairs the clearance of senescent and cancer cells and also disturbs the maintenance of energy metabolism and tissue proteostasis. The co-operation between senescent cells and immunosuppressive MDSCs regulates not only tumorigenesis and chronic inflammatory disorders but it also might promote inflammaging during the aging process.