Young Regulatory T Cell-Derived Extracellular Vesicles Improve Mitochondrial Function and Angiogenesis and Suppress Inflammation in Senescent Brain and Heart.

The core mechanisms underlying aging involve genomic instability, cellular senescence, mitochondrial dysfunction, and chronic inflammation, necessitating multi-dimensional therapeutic interventions. Treg-derived extracellular vesicles (Treg-EVs) therapy, which circumvents the safety risks associated with live cell therapies, exhibits the potential to modulate metabolic and immune functions, offering promise for healthy aging. Here, we isolated Tregs from young male C57BL/6 mice and collected Treg-EVs. In vitro experiments demonstrated that Treg-EVs significantly attenuated cellular senescence, reduced reactive oxygen species (ROS) accumulation, and enhanced mitochondrial respiration in HL-1 and HT22 senescent cell models. In vivo experimental data revealed that young Treg-EVs promoted mitochondrial biogenesis, facilitated vascular repair and regeneration, as well as attenuated inflammatory responses, and ultimately prolonged the survival of aged male C57BL/6 mice. This study demonstrates the ability of Treg-EVs therapy to reverse multiple aging-related abnormal phenotypes, providing a promising strategy for treating aging and its associated diseases.