Stimulation of RAS-dependent ROS signaling extends longevity by modulating a developmental program of global gene
Robyn Branicky1, Ying Wang1, Arman Khaki1
1Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada.
Abstract:
We show that elevation of mitochondrial superoxide generation increases Caenorhabditis elegans life span by enhancing a RAS-dependent ROS (reactive oxygen species) signaling pathway (RDRS) that controls the expression of half of the genome as well as animal composition and physiology. RDRS stimulation mimics a program of change in gene expression that is normally observed at the end of postembryonic development. We further show that RDRS is regulated by negative feedback from the superoxide dismutase 1 (SOD-1)-dependent conversion of superoxide into cytoplasmic hydrogen peroxide, which, in turn, acts on a redox-sensitive cysteine (C118) of RAS. Preventing C118 oxidation by replacement with serine, or mimicking oxidation by replacement with aspartic acid, leads to opposite changes in the expression of the same large set of genes that is affected when RDRS is stimulated by mitochondrial superoxide. The identities of these genes suggest that stimulation of the pathway extends life span by boosting turnover and repair while moderating damage from metabolic activity.
More Related Videos
07:25Lipid Supplementation for Longevity and Gene Transcriptional Analysis in Caenorhabditis elegans
Published on: December 9, 2022
10:05Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ
Published on: May 8, 2020
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
The Ras Gene
Ras is a...
Replicative Cell Senescence
Experimental RNAi
Regulation of Expression at Multiple Steps
PI3K/mTOR/AKT Signaling Pathway
