@inproceedings{2900788,
    title = "Nrf2 as a central hub in the wiring of proteostatic, mitostatic and metabolic pathways",
    author = "Ioannis P. Trougakos",
    year = "2017",
    pages = "12",
    publisher = "Hellenic Society of Biochemistry and Molecular Biology",
    booktitle = "68th Panhellenic Congress of the Hellenic Society of Biochemistry and Molecular Biology",
    keywords = "Proteostasis, Mitostasis, Nrf2, Metabolism, Ageing",
    abstract = "Metazoans respond to harmful challenges by mounting anti-stress responses. This adaptation along with the evolvement of metabolic networks, were fundamental forces during evolution. Central to anti-stress responses are a number of short-lived transcription factors that by functioning as stress sensors mobilize genomic responses aiming to eliminate stressors and restore tissue homeodynamics. We have found that increased expression of nuclear factor erythroid 2-related factor (Nrf2) in Drosophila flies activated cytoprotective modules and enhanced stress tolerance. However, while mild Nrf2 activation extended lifespan, high Nrf2 expression levels resulted in larvae lethality or, after inducible activation in adult flies, in altered mitochondrial bioenergetics; the appearance of diabetic phenotypes and reduced longevity. Genetic or dietary suppression of Insulin/IGF-like signaling (IIS) alleviated these effects and extended flies’ lifespan. Our observations indicate that prolonged stress signaling by otherwise cytoprotective short-lived stress sensors re-allocates resources from growth and longevity to somatic preservation and stress tolerance. They also suggest a role for potential dietary-restriction-like therapeutic interventions in various diseases of chronic stress including progeroid genome instability syndromes and/or neurodegeneration."
}