Spermidine, a polyamine that induces macroautophagy/autophagy, exhibits anti-aging properties. It is thought that these properties of spermidine are primarily due to its ability to modulate autophagy, but the mechanistic details were hitherto unclear. Studying the effects of spermidine on B lymphocytes, Zhang et al uncover the molecular mechanism that places spermidine at the crossroads of autophagy and immune senescence. Their work highlights the role of spermidine as an anti-aging metabolite that exerts its effects through the translational control of autophagy.Abbreviations: EIF5A, eukaryotic translation initiation factor 5A; HC, hematopoietic cell; ODC1, ornithine decarboxylase 1; PBMCs, peripheral blood mononuclear cells.