Aging modulates the immunosuppressive, polarizing and metabolic functions of blood-derived myeloid-derived suppressor cells (MDSCs)

With aging, the immune system undergoes immunosenescence, accompanied by chronic low-grade inflammation (inflammaging). Balanced immunity relies on effector and regulatory cells, with myeloid-derived suppressor cells (MDSCs) playing a key regulatory role. MDSCs, a heterogeneous population of immature myeloid cells, develop under inflammatory conditions and primarily suppress T cell activity. The age-dependent increase in myelopoiesis and inflammation, along with reduced immune reactivity, suggests that changes in the number and function of regulatory cells, such as MDSCs, might strongly contribute to age-related modifications of immune responses. While studies in mice have demonstrated an age-related increase in MDSC numbers, human studies have predominantly focused on cancer patients, making it challenging to separate the effects of aging and cancer on MDSC induction. Therefore, we analyzed MDSC increases in older individuals without a history of cancer. Furthermore, we excluded patients with neurodegenerative, cardiovascular or autoimmune diseases. We found a significant increase in circulating MDSCs in old donors. In addition, in vitro generated, blood-derived MDSCs from old donors exhibited enhanced immunosuppressive and Th2 polarizing capacity. RNA sequencing indicated age-related metabolic changes. These findings highlight that age-related changes in MDSCs contribute to dysregulated immune functions during aging.