Table I. Comparison of pathways pertinent in general aging to findings in T cell aging and differentiation
General Aging HallmarksaNaive T Cell Aging Hallmarks (Human)Hallmarks Associated with Naive T Cell Activation/Differentiation
Decline in regenerative capacity/stem cell exhaustionThymic involution, no evidence for homeostatic proliferation exhaustionNot applicable
Telomeric attritionTelomeric attritionTelomeric attrition
Genetic instability/DNA damageDefective DNA repair responses associated with premature naive T cell aging in rheumatoid arthritisIncreased DNA damage compared with naive T cells
Epigenetic alterationsNo dataPoised effector genes
Cellular senescenceInconclusive evidenceInduction of p16 with naive T cell activation
Metabolic processes/nutrient sensing/insulin-IGF pathwayNo dataAerobic glycolysis/oxidative phosphorylation pathways strictly linked with activation/differentiation
Mitochondrial dysfunctionNo dataIncreased mitochondrial capacity
Loss of proteostasisNo data in humans, autophagy defects in mouseAutophagy involved in T cell differentiation
Loss of stem cellness due to partial lineage commitmentPartial differentiation into memory cells (miRNA expression patterns, expression of CD25 and CD95)Full differentiation into memory T cells
  • a Modified from López-Otín et al. (9).