Immunity & Ageing

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

Amongst other sequelae, age-related skewing of haematopoiesis towards myelopoiesis may result in increased levels of myeloid-derived suppressor cells (MDSC) which are key players in inhibiting anti-tumour immunity and contribute to many other disease states. Keltsch et al. now provide evidence that both the induction and function of MDSC is exacerbated in older adults, potentially contributing to impaired T cell responses, at least in vitro. They investigated MDSC isolated either from peripheral blood or generated in vitro from circulating CD14+ cells. Ageing was associated with significantly increased numbers of both monocytic and polymorphonuclear MDSC populations. MDSC could be induced more efficiently from CD14+ cells of older adults and these suppressed T cell proliferation to a greater degree than MDSC from younger individuals. Serum from older and younger donors supported MDSC induction to a similar degree, but increased immunosuppressive activity of such MDSC was only supported by serum from the former. Elevated immunosuppressive activity of MDSC from old donors was associated with major metabolic changes and increased intracellular levels of neutral and oxidized lipids known to be immunosuppressive. Moreover, MDSC from older donors skewed T cell responses towards Th2 immunity which could further contribute to impaired cell-mediated immunity during ageing. These results may help to explain some of the age-related differences in human immunity.

^{Keltsch, E., Greiner, J., Wahl, L. et al. Aging modulates the immunosuppressive, polarizing and metabolic functions of blood-derived myeloid-derived suppressor cells (MDSCs). Immun Ageing 22, 29 (2025). https://doi.org/10.1186/s12979-025-00524-w}