Age-Related Microenvironment Toxicity Dictates T cells’ Immunity

Age-related morbidity, including the increased rate of infectious diseases, cancer, and autoimmune disorders, is hugely affected by the decline in immune potency. Aging affects all immune system compartments, with T lymphocytes being one of the most negatively affected populations. T cell activation relies on a well-tuned reprogramming of cellular metabolism. Aged T cells fail to induce the metabolic shift necessary for activation and proliferation. The reason for this failure is not known. In this study, we identified specific components accumulating in the aged lymphoid organ and show that aged T cells survive significantly better than young T cells when exposed to these signals. Moreover, exposing young T cells to the identified components was sufficient to drive multiple, aging-like, functional, and metabolic defects. These studies suggest that aged T cells adapt to survive in the toxic microenvironment of the aged lymphoid organ, at the expanse of losing their ability to respond to stimulation. And offer a new approach to restoring aged T cells’ metabolic functions by targeting their microenvironment.