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Juvenile Plasma Factors Improve Organ Function and Survival following Injury by Promoting Antioxidant Response

Xiaogang Chu1, Kumar Subramani1, Bobby Thomas2

  • 11Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912, USA.

Aging and Disease
|April 4, 2022
PubMed

Insights

Juvenile plasma factors rejuvenate aged mice after hemorrhagic shock. Extracellular vesicle treatment reduced oxidative stress and enhanced the Nrf2/Bach1 antioxidant pathway, prolonging survival.

Area of Science:

  • Gerontology
  • Hematology
  • Molecular Biology

Background:

  • Young organismal blood factors show rejuvenating effects on older ones.
  • Heterochronic parabiosis models support the hypothesis of juvenile factor-mediated rejuvenation.
  • Hemorrhagic shock poses significant risks to aged individuals.

Purpose of the Study:

  • To investigate the impact of juvenile plasma-derived factors on aged mice following hemorrhagic shock injury.
  • To elucidate the mechanisms underlying maturational dependence in injury resolution.

Main Methods:

  • Comparison of survival rates in young, mature, and aged mice subjected to hemorrhagic shock.
  • Administration of extracellular vesicles from young mice plasma to aged mice with hemorrhagic shock.
  • Analysis of oxidative stress markers, nuclear factor erythroid factor 2-related factor 2 (Nrf2) and its target genes, and BTB and CNC homology 1 (Bach1) expression.

Main Results:

  • Pre-pubertal mice exhibited prolonged survival post-hemorrhagic shock without fluid resuscitation compared to older mice.
  • Extracellular vesicle treatment significantly extended survival in aged mice subjected to hemorrhagic shock.
  • Treatment led to decreased oxidative stress and modulated the Nrf2/Bach1 axis, enhancing antioxidant response.

Conclusions:

  • Plasma factors from juvenile mice possess reparative properties for aged mice experiencing injury.
  • The Nrf2/Bach1 axis is a key pathway modulated by juvenile factors in resolving hemorrhagic shock injury.
  • Extracellular vesicles are potential therapeutic agents for mitigating age-related injury outcomes.

Keywords:
agingexosomesextracellular vesiclesjuvenile factorsshock

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