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Review
. 2019 Apr:134:702-707.
doi: 10.1016/j.freeradbiomed.2019.01.016. Epub 2019 Jan 14.

Redox regulation by NRF2 in aging and disease

Cody J Schmidlin  1 , Matthew B Dodson  1 , Lalitha Madhavan  2 , Donna D Zhang  3
Affiliations
Review

Redox regulation by NRF2 in aging and disease

Cody J Schmidlin et al. Free Radic Biol Med. 2019 Apr.

Abstract

NRF2, a transcription factor that has been deemed the master regulator of cellular redox homeostasis, declines with age. NRF2 transcriptionally upregulates genes that combat oxidative stress; therefore, loss of NRF2 allows oxidative stress to go unmitigated and drive the aging phenotype. Oxidative stress is a common theme among the key features associated with the aging process, collectively referred to as the "Hallmarks of Aging", as it disrupts proteostasis, alters genomic stability, and leads to cell death. In this review, we outline the role that oxidative stress and the reduction of NRF2 play in each of the Hallmarks of Aging, including how they contribute to the onset of neurodegenerative disorders, cancer, and other age-related pathologies.

Keywords: Age-related pathologies; Aging; Antioxidant response element (ARE); Cancer; KEAP1; NRF2; Neurodegeneration; Oxidative stress; Redox regulation.

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Figures

Figure 1.
Figure 1.. Loss of NRF2 and the Hallmarks of Aging.
Loss of NRF2 plays a direct role in each of the Hallmarks of Aging.
Figure 2.
Figure 2.. Oxidative stress and age related-pathologies.
Oxidative stress drives neurodegeneration, cancer, and age-related pathologies through organelle dysfunction, DNA damage, and protein aggregation. Target genes of NRF2 (GPX2, TXN1, GCLC, GCLM) facilitate the neutralization of free radicals and prevent damage from occurring. Accumulation of ROS results in mitochondrial dysfunction, DNA damage, and protein aggregates; NRF2 upregulates gene that combat these damages: BCL-2/BCL-xL, 53BP1/RAD51, and POMP/PSMA1 respectively. NRF2 mitigates age-related pathologies.
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