| RRC ID |
76125
|
| Author |
Branicky R, Wang Y, Khaki A, Liu JL, Kramer-Drauberg M, Hekimi S.
|
| Title |
Stimulation of RAS-dependent ROS signaling extends longevity by modulating a developmental program of global gene expression.
|
| Journal |
Sci Adv
|
| 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.
|
| Volume |
8(48)
|
| Pages |
eadc9851
|
| Published |
2022-12-2
|
| DOI |
10.1126/sciadv.adc9851
|
| PMID |
36449615
|
| PMC |
PMC9710873
|
| Resource |
| C.elegans |
tm783
tm760
tm1146 |
