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Branicky 2022 Sci Adv

From Bioblast
Publications in the MiPMap
Branicky R, Wang Y, Khaki A, Liu JL, Kramer-Drauberg M, Hekimi S (2022) Stimulation of RAS-dependent ROS signaling extends longevity by modulating a developmental program of global gene expression.

Β» Sci Adv 8:eadc9851. PMID: 36449615 Open Access

Branicky Robyn,  Wang Ying,  Khaki Arman, Liu Ju-Ling,  Kramer-Drauberg Maximilian, Hekimi Siegfried (2022) 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.

β€’ Bioblast editor: Plangger M

Labels: MiParea: Respiration, nDNA;cell genetics  Pathology: Aging;senescence 

Organism: Caenorhabditis elegans 

Preparation: Intact organism 

Coupling state: ROUTINE 

HRR: Oxygraph-2k