Exosome Release Delays Senescence by Disposing of Obsolete Biomolecules

Wenchong Zou, Mingqiang Lai, Yuanjun Jiang, Linlin Mao, Wu Zhou, Sheng Zhang, Pinglin Lai, Bin Guo, Tiantian Wei, Chengtao Nie, Lei Zheng, Jiahuan Zhang, Xuefei Gao, Xiaoyang Zhao, Laixin Xia, Zhipeng Zou, Anling Liu, Shiming Liu, Zhong Kai Cui*, Xiaochun Bai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Accumulation of obsolete biomolecules can accelerate cell senescence and organism aging. The two efficient intracellular systems, namely the ubiquitin-proteasome system and the autophagy-lysosome system, play important roles in dealing with cellular wastes. However, how multicellular organisms orchestrate the processing of obsolete molecules and delay aging remains unclear. Herein, it is shown that prevention of exosome release by GW4869 or Rab27a−/− accelerated senescence in various cells and mice, while stimulating exosome release by nutrient restriction delays aging. Interestingly, exosomes isolate from serum-deprived cells or diet-restricted human plasma, enriched with garbage biomolecules, including misfolded proteins, oxidized lipids, and proteins. These cellular wastes can be englobed by macrophages, eventually, for disintegration in vivo. Inhibition of nutrient-sensing mTORC1 signaling increases exosome release and delays senescence, while constitutive activation of mTORC1 reduces exosome secretion and exacerbates senescence in vitro and in mice. Notably, inhibition of exosome release attenuates nutrient restriction- or rapamycin-delayed senescence, supporting a key role for exosome secretion in this process. This study reveals a potential mechanism by which stimulated exosome release delays aging in multicellular organisms, by orchestrating the harmful biomolecules disposal via exosomes and macrophages.

Original languageEnglish
Article number2204826
JournalAdvanced Science
Volume10
Issue number8
DOIs
Publication statusPublished - 15 Mar 2023
Externally publishedYes

Keywords

  • aging
  • exosomes
  • mTORC1
  • nutrient restriction
  • obsolete biomolecules

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