ndus-8
C. elegans
putative NADH dehydrogenase
What the model saw
Gene: ndus-8 Organism: Caenorhabditis elegans Known functions: putative NADH dehydrogenase. 4 iron, 4 sulfur cluster binding. NADH dehydrogenase (ubiquinone) activity. NADH dehydrogenase activity. oxidoreductase activity, acting on NAD(P)H.
View unredacted entry
putative NADH dehydrogenase. 4 iron, 4 sulfur cluster binding. NADH dehydrogenase (ubiquinone) activity. NADH dehydrogenase activity. oxidoreductase activity, acting on NAD(P)H.
Solver output
ndus-8 encodes a subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), the first and largest enzyme of the electron transport chain. It contains a 4Fe-4S iron-sulfur cluster essential for electron transfer from NADH to ubiquinone. In C. elegans, partial loss-of-function of Complex I subunits (e.g., isp-1, nuo-6) is well-documented to extend lifespan by mildly reducing electron transport chain activity, lowering mitochondrial membrane potential, and reducing reactive oxygen species production — a phenomenon consistent with the mitohormesis model. However, the normal (wild-type) function of ndus-8 is to support full Complex I activity, which maintains efficient oxidative phosphorylation and mitochondrial homeostasis. Loss of this function extends lifespan, implying the gene's normal activity is anti-longevity in the context of C. elegans ETC biology. Yet, complete loss of Complex I is lethal, and the gene's core role in energy metabolism is essential. Given the established C. elegans paradigm where reduced Complex I activity promotes longevity, the wild-type pro-ETC function of ndus-8 is net anti-longevity relative to the reduced-function state.
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's mechanistic reasoning is actually correct - it correctly identifies that ndus-8 is a Complex I subunit, and correctly explains that in C. elegans, reduced Complex I activity extends lifespan (mitohormesis), meaning the wild-type gene's function is anti-longevity. However, the model then contradicts itself by outputting "pro_longevity" as its final prediction, despite its own reasoning clearly pointing to "anti_longevity." The ground truth is "anti_longevity." The model's reasoning correctly arrives at the anti-longevity conclusion but then submits the wrong final answer. This is a case where the reasoning is sound but the final answer label is incorrect - a self-contradiction within the response. The confidence of 0.55 reflects some uncertainty, but the model still chose the wrong label despite its own analysis supporting the correct one.
Raw API responses
solver
{
"reasoning": "ndus-8 encodes a subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), the first and largest enzyme of the electron transport chain. It contains a 4Fe-4S iron-sulfur cluster essential for electron transfer from NADH to ubiquinone. In C. elegans, partial loss-of-function of Complex I subunits (e.g., isp-1, nuo-6) is well-documented to extend lifespan by mildly reducing electron transport chain activity, lowering mitochondrial membrane potential, and reducing reactive oxygen species production — a phenomenon consistent with the mitohormesis model. However, the normal (wild-type) function of ndus-8 is to support full Complex I activity, which maintains efficient oxidative phosphorylation and mitochondrial homeostasis. Loss of this function extends lifespan, implying the gene's normal activity is anti-longevity in the context of C. elegans ETC biology. Yet, complete loss of Complex I is lethal, and the gene's core role in energy metabolism is essential. Given the established C. elegans paradigm where reduced Complex I activity promotes longevity, the wild-type pro-ETC function of ndus-8 is net anti-longevity relative to the reduced-function state.",
"confidence": 0.55,
"key_pathways": [
"Mitochondrial Complex I / electron transport chain",
"NADH:ubiquinone oxidoreductase activity",
"Mitohormesis / ROS signaling"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model's mechanistic reasoning is actually correct - it correctly identifies that ndus-8 is a Complex I subunit, and correctly explains that in C. elegans, reduced Complex I activity extends lifespan (mitohormesis), meaning the wild-type gene's function is anti-longevity. However, the model then contradicts itself by outputting \"pro_longevity\" as its final prediction, despite its own reasoning clearly pointing to \"anti_longevity.\" The ground truth is \"anti_longevity.\" The model's reasoning correctly arrives at the anti-longevity conclusion but then submits the wrong final answer. This is a case where the reasoning is sound but the final answer label is incorrect - a self-contradiction within the response. The confidence of 0.55 reflects some uncertainty, but the model still chose the wrong label despite its own analysis supporting the correct one.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}