Cellular senescence has beneficial functions in embryonic development, wound healing and tumour suppression but can also be maladaptive, contributing to cancer development and disease. This Review describes the mechanisms, hallmarks and consequences of senescence, as well as the therapeutic potential of senescence-targeting interventions.

Two recent randomized trials provide evidence to guide the management of sepsis. The CLASSIC trial reports that restrictive fluid therapy has no mortality benefit compared to a standard regimen in patients with septic shock, whereas the LOVIT trial reports that high-dose intravenous vitamin C might be harmful in patients with severe sepsis.

Necroptosis is a form of regulated necrosis in which RIPK3 is activated by binding to RIP homotypic interaction motif (RHIM)-containing proteins. Now, researchers describe a non-canonical pathway of RIPK3 activation that is triggered by osmotic stress and NHE1-mediated cytosol alkalinization. This previously undescribed mechanism of osmotic stress-induced necroptosis might have implications for treating cancer and other diseases.

Alloimmune T cell responses have a crucial role in graft rejection. Here, the authors examine the factors that regulate T cell activation, differentiation and function in secondary lymphoid organs and in the graft, including the different pathways of allorecognition, innate–adaptive immunity crosstalk and the role of survival cytokines.