idh-1
C. elegans
Isocitrate dehydrogenase
What the model saw
Gene: idh-1 Organism: Caenorhabditis elegans Known functions: Isocitrate dehydrogenase. NAD binding. isocitrate dehydrogenase (NADP+) activity. magnesium ion binding. oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor.
View unredacted entry
Isocitrate dehydrogenase. NAD binding. isocitrate dehydrogenase (NADP+) activity. magnesium ion binding. oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor.
Solver output
IDH-1 is an isocitrate dehydrogenase that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate in the TCA cycle, using NADP+ as a cofactor. This reaction is a critical node in mitochondrial energy metabolism, generating NADPH which is a key reducing equivalent for antioxidant defense (e.g., maintaining glutathione in its reduced form). In C. elegans, alpha-ketoglutarate produced by this reaction is also a known longevity-promoting metabolite that inhibits ATP synthase and TOR signaling. Adequate IDH-1 activity supports mitochondrial redox homeostasis and reduces oxidative stress, both of which are associated with extended lifespan. Loss of idh-1 function in C. elegans has been shown to reduce lifespan, consistent with a pro-longevity role for the wild-type gene.
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 ultimately wrong. It argues that IDH-1 is pro-longevity because loss of function reduces lifespan — but that logic actually supports a pro_longevity classification only if the gene's normal role is to extend life. However, the GenAge database classifies idh-1 as anti_longevity, meaning that overexpression or gain of function reduces lifespan (or loss of function extends it). The model's mechanistic reasoning about NADPH production, alpha-ketoglutarate, and TOR signaling is plausible in general but is applied incorrectly here. The model also states "Loss of idh-1 function in C. elegans has been shown to reduce lifespan" — if this were true, it would indeed support pro_longevity, but the ground truth contradicts this claim, suggesting the model may have hallucinated or misremembered this specific experimental result. The confidence of 0.72 is relatively high for an incorrect answer.
Raw API responses
solver
{
"reasoning": "IDH-1 is an isocitrate dehydrogenase that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate in the TCA cycle, using NADP+ as a cofactor. This reaction is a critical node in mitochondrial energy metabolism, generating NADPH which is a key reducing equivalent for antioxidant defense (e.g., maintaining glutathione in its reduced form). In C. elegans, alpha-ketoglutarate produced by this reaction is also a known longevity-promoting metabolite that inhibits ATP synthase and TOR signaling. Adequate IDH-1 activity supports mitochondrial redox homeostasis and reduces oxidative stress, both of which are associated with extended lifespan. Loss of idh-1 function in C. elegans has been shown to reduce lifespan, consistent with a pro-longevity role for the wild-type gene.",
"confidence": 0.72,
"key_pathways": [
"TCA cycle / alpha-ketoglutarate production",
"NADPH-dependent antioxidant defense",
"TOR signaling inhibition via alpha-ketoglutarate"
],
"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 ultimately wrong. It argues that IDH-1 is pro-longevity because loss of function reduces lifespan — but that logic actually supports a pro_longevity classification only if the gene's normal role is to extend life. However, the GenAge database classifies idh-1 as anti_longevity, meaning that overexpression or gain of function reduces lifespan (or loss of function extends it). The model's mechanistic reasoning about NADPH production, alpha-ketoglutarate, and TOR signaling is plausible in general but is applied incorrectly here. The model also states \"Loss of idh-1 function in C. elegans has been shown to reduce lifespan\" — if this were true, it would indeed support pro_longevity, but the ground truth contradicts this claim, suggesting the model may have hallucinated or misremembered this specific experimental result. The confidence of 0.72 is relatively high for an incorrect answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}