T cell metabolic ageing as a factor for therapeutic research

Abstract

Ageing is an important determinant of immune function across the lifespan, yet it remains underappreciated in the design and interpretation of much basic T cell research. As the immune system ages, T cell responses become less diverse, less efficient, and less adaptable, with consequences for infection control, vaccine responsiveness, cancer immunosurveillance, and the performance of T cell-based immunotherapies. This issue is particularly acute because many fundamental studies still rely on T cells from, mostly, healthy young donors. These controls are indispensable, but the field has built much of its pre-clinical logic on immune systems that are younger, fitter, and biologically distinct from the patients for whom T cell therapies are intended. We argue that this mismatch between experimental systems and clinical reality could be overcome by considering age as a routine variable from the start.