T cell survival, differentiation after stimulation, and function are intrinsically linked to distinct cellular metabolic states. The ability of T cells to readily transition between metabolic states enables flexibility to meet the changing energy demands defined by distinct effector states or T cell lineages. Immune aging is characterized, in part, by the loss of naïve T cells, accumulation of senescent T cells, severe dysfunction in memory phenotype T cells in particular, and elevated levels of inflammatory cytokines, or ‘inflammaging’. Here, we review our current understanding of the phenotypic and functional changes that occur with aging in T cells, and how they relate to metabolic changes in the steady state and after T cell activation. We discuss the apparent contradictions in the aging T cell phenotype - where enhanced differentiation states and metabolic profiles in the steady state can correspond to a diminished capacity to adapt metabolically and functionally after T cell activation. Finally, we discuss key recent studies that indicate the enormous potential for aged T cell metabolism to induce systemic inflammaging and organism-wide multimorbidity, resulting in premature death.

hematopoietic stem cells

oxidative phosphorylation

mucosal-associated invariant T cell

virtual memory T cell

effector memory T cell re-expressing CD45RA

antigen-experienced memory T cell

mammalian target of rapamycin

pentose phosphate pathway

spare respiratory capacity

hypoxia inhibitory factor 1α

reactive oxygen species

T cells

Aging

Metabolism

Unconventional T cells

Organismal aging

T cell dysfunction

© 2023 The Author(s). Published by Elsevier Ltd.