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The Nrf2-HO-1 system and inflammaging.

Sinead A O'Rourke1,2, Lianne C Shanley1,2, Aisling Dunne1,2,3

  • 1School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.

Frontiers in Immunology
|October 9, 2024
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Summary
This summary is machine-generated.

The Nrf2-HO-1 pathway combats oxidative stress and inflammation, crucial for combating aging. Activating this system may offer therapeutic benefits for age-related diseases.

Keywords:
Nrf2agingheme oxygenaseinflammagingoxidative stress

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Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Gerontology

Background:

  • Oxidative stress contributes significantly to aging and chronic inflammation, a process termed 'inflammaging'.
  • The transcription factor Nrf2 regulates genes, including heme oxygenase-1 (HO-1), involved in cellular defense against oxidative stress.
  • HO-1's catabolism products possess antioxidant and anti-inflammatory properties, showing therapeutic potential in inflammatory and autoimmune diseases.

Purpose of the Study:

  • To review the role of oxidative stress in 'inflammaging'.
  • To highlight the anti-aging potential of the Nrf2-HO-1 system.
  • To discuss Nrf2 activators and their therapeutic applications in age-related diseases.

Main Methods:

  • Literature review of studies on Nrf2, HO-1, oxidative stress, and aging.
  • Analysis of the role of Nrf2 and HO-1 in cellular senescence and SASP.
  • Examination of established and emerging Nrf2 activators.

Main Results:

  • Nrf2 activity declines with age, exacerbating oxidative stress and inflammation.
  • Nrf2 and HO-1 can reduce cellular senescence and the senescence-associated secretory phenotype (SASP).
  • Nrf2 activators show promise for treating age-related inflammatory conditions.

Conclusions:

  • The Nrf2-HO-1 pathway is a key regulator of cellular response to oxidative stress and inflammation.
  • Targeting the Nrf2-HO-1 system offers a promising strategy for mitigating 'inflammaging' and age-related diseases.
  • Further research into Nrf2 activators could lead to novel anti-aging therapies.