Regulatory T cells (Tregs) are crucial for maintaining self-tolerance and preventing autoimmune disease. During aging, cellular senescence of Tregs and their dysfunctional state may contribute to age-related diseases fueled by chronic inflammation in the elderly – also called “inflammaging”. The T cell-intrinsic factors, as well as factors released from dysfunctional cells that could lead to alteration of the metabolic state of recipient T cells during aging, are currently ill-defined. In autoimmune disease patients, Tregs display metabolic changes, mitochondrial dysfunction, and oxidative stress signatures similar to cellular senescence, linking T cell aging and autoimmunity. The main objective of team TDA is to understand the molecular mechanisms governing immune senescence and metabolic dysfunction in Tregs and other T cell subsets that are shared in autoimmunity and aging. This project will conceive novel in vitro models that combine proteomics and single-cell transcriptomics with gene-editing techniques to identify and validate robust molecular signatures during disease development. Team TDA’s final goal is to improve patient outcomes by delivering new targets and novel therapeutic approaches for autoimmune disease treatment and for balancing immune responses in the elderly.