This review explores how aging transforms the T cell landscape, leading to a decline in immune flexibility and increased vulnerability to disease. The authors detail how the progressive atrophy of the thymus reduces the production of new naive T cells, while lifelong exposure to pathogens causes the remaining memory T cell pool to become highly specialized but functionally constrained. These shifts are driven by complex molecular mechanisms, including telomere shortening, mitochondrial dysfunction, and epigenetic remodeling, which collectively promote a state of chronic low-grade inflammation known as inflammaging. Consequently, elderly individuals often experience weakened responses to new infections and vaccinations, as their immune systems prioritize the persistence of old memories over the ability to adapt to new threats. Finally, the text evaluates emerging rejuvenation strategies, such as metabolic reprogramming and cytokine therapies, aimed at restoring immune vigor and extending a healthy lifespan.

References:

• Adamo S, Rurik J G, Gustafson C E, et al. Memory T cell aging and rejuvenation[J]. Immunity, 2026.