nduf-2.2
C. elegans
Complex I-49kD
What the model saw
Gene: nduf-2.2 Organism: Caenorhabditis elegans Known functions: Complex I-49kD. NAD binding. NADH dehydrogenase (ubiquinone) activity. oxidoreductase activity, acting on NAD(P)H. quinone binding.
View unredacted entry
Complex I-49kD. NAD binding. NADH dehydrogenase (ubiquinone) activity. oxidoreductase activity, acting on NAD(P)H. quinone binding.
Solver output
nduf-2.2 encodes the 49 kDa subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), which catalyzes the transfer of electrons from NADH to ubiquinone via its NAD-binding and quinone-binding domains. In C. elegans, partial loss-of-function of Complex I subunits (e.g., gas-1, nuo-1, and related nduf genes) is well-documented to extend lifespan through a mitohormesis mechanism: mild impairment of electron transport chain activity reduces ATP production and increases mitochondrial ROS signaling at low levels, activating stress-response pathways such as the mitochondrial unfolded protein response (UPRmt) and DAF-16/FOXO. The normal function of nduf-2.2 thus supports full Complex I activity, and its intact operation is associated with wild-type (shorter) lifespan relative to partial loss-of-function states; however, as a core ETC component, complete loss is lethal. The gene's primary molecular role in oxidoreductase/electron transport places it squarely in the mitochondrial dysfunction hallmark of aging. The pro-longevity classification reflects the established paradigm that reduced Complex I activity—not its presence—extends lifespan, meaning the gene's normal function opposes the longevity-extending mitohormetic 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 predicted "pro_longevity" but the ground truth is "anti_longevity." The model's reasoning is internally contradictory and confused. It correctly identifies that loss of Complex I subunits can extend lifespan via mitohormesis, but then incorrectly labels nduf-2.2 as "pro_longevity" — arguing that the gene's normal function "opposes the longevity-extending mitohormetic state." This is a fundamental misunderstanding of the GenAge classification system: a gene is "anti_longevity" when its normal function shortens lifespan (i.e., loss-of-function extends lifespan), which is exactly what the model describes. The model's mechanistic narrative actually supports the correct answer (anti_longevity) but it mislabels the classification. The reasoning is self-contradictory: it says the gene's intact operation is associated with shorter lifespan, yet classifies it as pro_longevity. This reflects a confusion between the gene's function and the longevity classification convention.
Raw API responses
solver
{
"reasoning": "nduf-2.2 encodes the 49 kDa subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), which catalyzes the transfer of electrons from NADH to ubiquinone via its NAD-binding and quinone-binding domains. In C. elegans, partial loss-of-function of Complex I subunits (e.g., gas-1, nuo-1, and related nduf genes) is well-documented to extend lifespan through a mitohormesis mechanism: mild impairment of electron transport chain activity reduces ATP production and increases mitochondrial ROS signaling at low levels, activating stress-response pathways such as the mitochondrial unfolded protein response (UPRmt) and DAF-16/FOXO. The normal function of nduf-2.2 thus supports full Complex I activity, and its intact operation is associated with wild-type (shorter) lifespan relative to partial loss-of-function states; however, as a core ETC component, complete loss is lethal. The gene's primary molecular role in oxidoreductase/electron transport places it squarely in the mitochondrial dysfunction hallmark of aging. The pro-longevity classification reflects the established paradigm that reduced Complex I activity—not its presence—extends lifespan, meaning the gene's normal function opposes the longevity-extending mitohormetic state.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial electron transport chain (Complex I)",
"mitohormesis / mitochondrial UPR (UPRmt)",
"DAF-16/FOXO stress response"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" The model's reasoning is internally contradictory and confused. It correctly identifies that loss of Complex I subunits can extend lifespan via mitohormesis, but then incorrectly labels nduf-2.2 as \"pro_longevity\" — arguing that the gene's normal function \"opposes the longevity-extending mitohormetic state.\" This is a fundamental misunderstanding of the GenAge classification system: a gene is \"anti_longevity\" when its normal function shortens lifespan (i.e., loss-of-function extends lifespan), which is exactly what the model describes. The model's mechanistic narrative actually supports the correct answer (anti_longevity) but it mislabels the classification. The reasoning is self-contradictory: it says the gene's intact operation is associated with shorter lifespan, yet classifies it as pro_longevity. This reflects a confusion between the gene's function and the longevity classification convention.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}