gst-10
C. elegans
Glutathione S-transferase P 10;glutathione transferase
What the model saw
Gene: gst-10 Organism: Caenorhabditis elegans Known functions: Glutathione S-transferase P 10;glutathione transferase. glutathione transferase activity.
View unredacted entry
Glutathione S-transferase P 10;glutathione transferase. glutathione transferase activity.
Solver output
Glutathione S-transferases (GSTs) catalyze the conjugation of glutathione to electrophilic substrates, serving as a primary enzymatic defense against oxidative stress and xenobiotic toxicity. In C. elegans, gst-10 encodes a Pi-class GST that detoxifies reactive oxygen species (ROS)-derived lipid peroxidation products (e.g., 4-hydroxynonenal) and other electrophiles, thereby reducing oxidative damage to macromolecules. GST activity is a downstream effector of the DAF-16/FOXO and SKN-1/Nrf2 transcription factor pathways, which are central regulators of longevity in C. elegans; long-lived daf-2 insulin/IGF-1 receptor mutants upregulate multiple gst genes. By mitigating mitochondria-derived ROS damage and maintaining redox homeostasis, gst-10 function is expected to oppose age-associated oxidative deterioration and support lifespan extension.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model correctly predicted pro_longevity for gst-10. However, the mechanism class is labeled "mitochondrial_dysfunction," which is inaccurate and inconsistent with the reasoning provided. The actual mechanism described in the reasoning is oxidative stress defense / detoxification (glutathione conjugation, ROS scavenging, lipid peroxidation product detoxification), not mitochondrial dysfunction per se. The reasoning itself is largely sound — GSTs do serve as antioxidant/detoxification enzymes and are regulated by DAF-16/FOXO and SKN-1/Nrf2 pathways — but the mechanism_class label is a mismatch. The reasoning is plausible and generally correct in its biological description, but the classification of the mechanism as "mitochondrial_dysfunction" is a notable error.
Raw API responses
solver
{
"reasoning": "Glutathione S-transferases (GSTs) catalyze the conjugation of glutathione to electrophilic substrates, serving as a primary enzymatic defense against oxidative stress and xenobiotic toxicity. In C. elegans, gst-10 encodes a Pi-class GST that detoxifies reactive oxygen species (ROS)-derived lipid peroxidation products (e.g., 4-hydroxynonenal) and other electrophiles, thereby reducing oxidative damage to macromolecules. GST activity is a downstream effector of the DAF-16/FOXO and SKN-1/Nrf2 transcription factor pathways, which are central regulators of longevity in C. elegans; long-lived daf-2 insulin/IGF-1 receptor mutants upregulate multiple gst genes. By mitigating mitochondria-derived ROS damage and maintaining redox homeostasis, gst-10 function is expected to oppose age-associated oxidative deterioration and support lifespan extension.",
"confidence": 0.72,
"key_pathways": [
"Glutathione-mediated detoxification / ROS scavenging",
"DAF-16/FOXO and SKN-1/Nrf2 stress-response transcription",
"Lipid peroxidation product detoxification (4-HNE conjugation)"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for gst-10. However, the mechanism class is labeled \"mitochondrial_dysfunction,\" which is inaccurate and inconsistent with the reasoning provided. The actual mechanism described in the reasoning is oxidative stress defense / detoxification (glutathione conjugation, ROS scavenging, lipid peroxidation product detoxification), not mitochondrial dysfunction per se. The reasoning itself is largely sound — GSTs do serve as antioxidant/detoxification enzymes and are regulated by DAF-16/FOXO and SKN-1/Nrf2 pathways — but the mechanism_class label is a mismatch. The reasoning is plausible and generally correct in its biological description, but the classification of the mechanism as \"mitochondrial_dysfunction\" is a notable error.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": true,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}