CD4⁺ T cells confer transplantable rejuvenation via Rivers of telomeres

Abstract

The role of the immune system in regulating organismal lifespan remains poorly understood. Here, we show that CD4+ T cells release telomere Rivers into circulation after acquiring telomeres from antigen-presenting cells (APCs). River formation requires fatty acid oxidation at the immune synapse, which selectively excludes glyceraldehyde 3 phosphate dehydrogenase (GAPDH) from the telomere vesicles. The resulting Rivers are depleted of glycolytic enzymes but enriched in T cell derived stemness factors, enabling targeted rejuvenation of senescent tissues across multiple organs. In aged mice, adoptive transfer of young or metabolically reprogrammed CD4+ T cells triggered River production in vivo, and Rivers isolated from these animals could be transplanted into other aged mice to propagate the rejuvenation phenotype independently of T cells. River therapy extended median lifespan by ~17 months, with several mice surviving to nearly five years. This immune-driven telomere transfer pathway is conserved across kingdoms, including plants, defining the first systemic, transplantable programme of youth.