Figure 1.

Hallmarks of cellular and metabolic senescence and/or aging in T cells. (A) Key characteristics of cellular senescence include DNA damage and telomere erosion that contribute to genomic instability and dysregulation of the epigenome. Phenotypically, T cell senescence is associated with a loss of surface CD28 expression and the upregulation of innate T cell markers such as the killer cell immunoglobulin-like receptors (KIRs). The involution of the thymus increases the homeostatic pressure on T cells. Senescent T cells, however, show a diminished capacity for homeostatic proliferation, and additionally feature reduced T cell receptor (TCR) reactivity. Another hallmark of T cell senescence is the production of pro-inflammatory mediators, collectively known as senescence-associated secretory phenotype (SASP). (B) Key metabolic characteristics associated with T cell senescence and aging often closely interwoven and include a decline in the respiratory capacity or efficacy and substantially altered engagement of glycolysis, as well as alterations in the pathways used to fuel the tricarboxylic acid (TCA) cycle, which are likely context- and cell subset-dependent. The same holds true for the dysbalanced lipid metabolism observed in senescent/aged T cells. In addition, ratios of coenzymes for metabolic reactions such as NAD/NADH that are crucial for balancing the cellular redox state are shifted in senescent cells. Furthermore, reactive oxygen species (ROS) accumulate and eventually cause DNA and protein damage. Damaged organelles, cell membranes and proteins are usually degraded by autophagy, another pivotal mechanism that is attenuated by the aging or the senescent process.