Nrf2 Plays a Key Role in Erythropoiesis during Aging
Serge Cedrick Toya Mbiandjeu1, Angela Siciliano2,3, Alessandro Mattè1
1Department of Medicine, University of Verona, 37134 Verona, Italy.
Antioxidants (Basel, Switzerland)
|April 27, 2024
Summary
The antioxidant pathway regulated by Nuclear factor erythroid-2-related factor (Nrf2) is crucial for preventing age-related anemia. Loss of Nrf2 impairs red blood cell production and survival, leading to anemia in aging mice.
Area of Science:
- Gerontology
- Hematology
- Molecular Biology
Background:
- Aging is associated with increased oxidative stress and declining cellular defense mechanisms.
- Nuclear factor erythroid-2-related factor (Nrf2) is a master regulator of antioxidant and cytoprotective genes.
- The role of Nrf2 in erythroid biology during aging remains incompletely understood.
Purpose of the Study:
- To investigate the role of Nrf2 in age-related anemia and erythroid maturation.
- To elucidate the molecular mechanisms underlying Nrf2's function in aging erythrocytes.
- To evaluate the therapeutic potential of antioxidant intervention in Nrf2-deficient aging mice.
Main Methods:
- Comparative analysis of Nrf2-deficient (Nrf2-/-) and wild-type mice during aging.
- Assessment of erythropoiesis, red blood cell lifespan, and oxidative stress markers.
- Investigation of unfolded protein response (UPR) and autophagy pathways in erythroblasts.
- Pharmacological intervention using antioxidant-loaded nanoparticles (astaxanthin-PLGA).
Main Results:
- Nrf2-/- mice exhibited age-dependent anemia characterized by reduced red blood cell lifespan and ineffective erythropoiesis.
- Absence of Nrf2 led to persistent oxidative stress, impaired autophagy, and overactivated UPR in erythroblasts.
- These cellular dysregulations in Nrf2-/- erythroblasts promoted apoptosis via caspase-3 activation.
- Treatment with astaxanthin nanoparticles ameliorated anemia and ineffective erythropoiesis in Nrf2-/- mice.
Conclusions:
- Nrf2 is essential for maintaining erythroid health and preventing anemia during aging.
- Nrf2 mitigates age-related oxidative stress and regulates crucial cellular processes like UPR and autophagy in erythroid cells.
- Targeting Nrf2-mediated antioxidant pathways, such as with astaxanthin, offers a potential therapeutic strategy for age-related hematological disorders.
Keywords:
ATF6GADD34PLGAUPR systemastaxanthinautophagyineffective erythropoiesisnanoparticlesoxidationred cellsMore Related Videos
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