p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8^sup +^ T cells

T cell senescence is thought to contribute to immune function decline, but the pathways that mediate senescence in these cells are not clear. In this article, the researchers evaluated T cell populations from healthy volunteers and determined that human CD8^sup +^ effector memory T cells that reexpress the naive T cell marker CD45RA have many characteristics of cellular senescence, including decreased proliferation, defective mitochondrial function, and elevated levels of both ROS and p38 MAPK. Despite their apparent senescent state, they determined that these cells secreted high levels of both TNF-α and IFN-γ and showed potent cytotoxic activity. The researchers found that the senescent CD45RA-expressing population engaged anaerobic glycolysis to generate energy for effector functions. Furthermore, inhibition of p38 MAPK signaling in senescent CD8^sup +^ T cells increased their proliferation, telomerase activity, mitochondrial biogenesis, and fitness; however, the extra energy required for these processes did not arise from increased glucose uptake or oxidative phosphorylation.