Title:
Nrf2 as a main hub in the wiring of proteostatic, mitostatic and metabolic pathways
Languages of Item:
English
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.
Authors:
Eleni N. Tsakiri
Sentiljana Gumeni
Kalliopi K. Iliaki
Dimitra Benaki
Konstantinos Vougas
Gerasimos P. Sykiotis,
Vassilis G. Gorgoulis
Emmanuel Mikros
Luca Scorrano
Ioannis P. Trougakos
Publisher:
COST ACTION BM1307 PROTEOSTASIS
Conference title:
Proteostatic Mechanisms in Health & Disease
Keywords:
Proteostasis, Mitostasis, Metabolism, Ageing, Nrf2
Main subject category:
Health Sciences
Project information:
EU projects TASCMAR (EU-H2020, GA 634674) and MEDIHEALTH (H2020-MSCA-RISE-2015, GA 691158)
