New strategies to rejuvenate immunity

The thesis "New Strategies to Rejuvenate Immunity" explores novel therapeutic approaches to combat immunosenescence, the age-related decline of immune function. Immunosenescence leads to increased susceptibility to infections, autoimmune diseases, and decreased vaccine efficacy in elderly populations. This PhD project focuses on targeting T cells, which are critical for adaptive immunity, to restore their functionality and improve immune responses. The first key finding involves the disruption of the sestrin-mitogen activated kinase (MAPK) protein complex (sMAC), which is responsible for driving T cell senescence. By developing Disruptors of sMAC (DOS) compounds, the study demonstrates how inhibiting the sestrin-MAPK interaction can reverse T cell aging. DOS compounds degrade sestrins, reprogramming T cells into a more youthful, stem-like state, thereby restoring their proliferative capacity and enhancing immune responses. This rejuvenation offers potential for improving immunity in elderly populations. The second major discovery is the identification of a novel telomere transfer mechanism. Antigen-presenting cells (APCs) can transfer telomeres to T cells via extracellular vesicles, elongating their telomeres and increasing their lifespan. This process generates long-lived memory T cells, which are crucial for sustaining immune memory and for responding effectively to infections and vaccines. Telomere transfer presents significant potential for improving immune function in aging populations and in cancer immunotherapy. The thesis also applies these findings to autoimmune diseases, specifically multiple sclerosis (MS). By restoring telomere length in T cells, the study shows the potential to reverse T-cell senescence, reduce neuroinflammation, and improve disease outcomes in MS mouse model. Overall, the research provides groundbreaking insights into immune rejuvenation and offers new avenues for treating immunosenescence and autoimmune diseases. These findings pave the way for innovative therapeutic strategies to enhance human health and longevity.