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Disrupting the SKN-1 homeostat: mechanistic insights and phenotypic outcomes.
- Source :
- Frontiers in Aging Neuroscience; 2024, p1-15, 15p
- Publication Year :
- 2024
-
Abstract
- The mechanisms that govern maintenance of cellular homeostasis are crucial to the lifespan and healthspan of all living systems. As an organism ages, there is a gradual decline in cellular homeostasis that leads to senescence and death. As an organism lives into advanced age, the cells within will attempt to abate age-related decline by enhancing the activity of cellular stress pathways. The regulation of cellular stress responses by transcription factors SKN-1/Nrf2 is a well characterized pathway in which cellular stress, particularly xenobiotic stress, is abated by SKN-1/Nrf2-mediated transcriptional activation of the Phase II detoxification pathway. However, SKN-1/Nrf2 also regulates a multitude of other processes including development, pathogenic stress responses, proteostasis, and lipid metabolism. While this process is typically tightly regulated, constitutive activation of SKN-1/Nrf2 is detrimental to organismal health, this raises interesting questions surrounding the tradeoff between SKN-1/Nrf2 cryoprotection and cellular health and the ability of cells to deactivate stress response pathways post stress. Recent work has determined that transcriptional programs of SKN-1 can be redirected or suppressed to abate negative health outcomes of constitutive activation. Here we will detail the mechanisms by which SKN-1 is controlled, which are important for our understanding of SKN-1/Nrf2 cytoprotection across the lifespan. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16634365
- Database :
- Complementary Index
- Journal :
- Frontiers in Aging Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 176108746
- Full Text :
- https://doi.org/10.3389/fragi.2024.1369740