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

  • J Neurochem. 2026 Mar;170(3):e70402. doi: 10.1111/jnc.70402.
Jiahui Cheng  1 ,  Yiyang Xia  2 ,  Zhiqiang Ji  1 ,  Lingling Xu  1 ,  Rifeng Gao  3 ,  Zhi Xiong  4 ,  Lili Huang  5 ,  Xiao Zhang  5 ,  Weina Ding  1 ,  Yawen Sun  1 ,  Shiteng Suo  1 ,  Bo Li  1  5 ,  Yan Zhou  1
Affiliations
  • 1. Department of Radiology, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2. Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3. Department of Cardiac Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 4. Institute of Diagnostic and Interventional Radiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5. Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China.
PMID: 41797211 DOI: 10.1111/jnc.70402
Abstract

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.

Keywords
Treg‐derived extracellular vesicles; aging; angiogenesis; inflammation; mitochondrial biogenesis.
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