TY - JOUR
T1 - Exosome Release Delays Senescence by Disposing of Obsolete Biomolecules
AU - Zou, Wenchong
AU - Lai, Mingqiang
AU - Jiang, Yuanjun
AU - Mao, Linlin
AU - Zhou, Wu
AU - Zhang, Sheng
AU - Lai, Pinglin
AU - Guo, Bin
AU - Wei, Tiantian
AU - Nie, Chengtao
AU - Zheng, Lei
AU - Zhang, Jiahuan
AU - Gao, Xuefei
AU - Zhao, Xiaoyang
AU - Xia, Laixin
AU - Zou, Zhipeng
AU - Liu, Anling
AU - Liu, Shiming
AU - Cui, Zhong Kai
AU - Bai, Xiaochun
N1 - Publisher Copyright:
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
PY - 2023/3/15
Y1 - 2023/3/15
N2 - 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.
AB - 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.
KW - aging
KW - exosomes
KW - mTORC1
KW - nutrient restriction
KW - obsolete biomolecules
UR - http://www.scopus.com/inward/record.url?scp=85146710392&partnerID=8YFLogxK
U2 - 10.1002/advs.202204826
DO - 10.1002/advs.202204826
M3 - Article
C2 - 36683247
AN - SCOPUS:85146710392
SN - 2198-3844
VL - 10
JO - Advanced Science
JF - Advanced Science
IS - 8
M1 - 2204826
ER -