Stimulation of RAS-dependent ROS signaling extends longevity by modulating a developmental program of global gene expression.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36449615.
- Also identified by DOI 10.1126/sciadv.adc9851 and PMC identifier 9710873.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
We show that elevation of mitochondrial superoxide generation increases <i>Caenorhabditis elegans</i> 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.