acdh-13
C. elegans
Acyl-CoA dehydrogenase family member 9, mitochondrial
What the model saw
Gene: acdh-13 Organism: Caenorhabditis elegans Known functions: Acyl-CoA dehydrogenase family member 9, mitochondrial. acyl-CoA dehydrogenase activity. flavin adenine dinucleotide binding. oxidoreductase activity, acting on the CH-CH group of donors.
View unredacted entry
Acyl-CoA dehydrogenase family member 9, mitochondrial. acyl-CoA dehydrogenase activity. flavin adenine dinucleotide binding. oxidoreductase activity, acting on the CH-CH group of donors.
Solver output
acdh-13 encodes a mitochondrial acyl-CoA dehydrogenase (ortholog of human ACAD9), which catalyzes the first step of mitochondrial fatty acid β-oxidation by introducing a trans-double bond into acyl-CoA substrates using FAD as a cofactor. Efficient β-oxidation is essential for maintaining mitochondrial energy homeostasis and lipid metabolism, both of which are critical determinants of lifespan in C. elegans. ACAD9 in particular is also known to function as an assembly factor for mitochondrial respiratory chain Complex I; loss of Complex I assembly impairs oxidative phosphorylation and increases ROS production, hallmarks of mitochondrial dysfunction associated with accelerated aging. Proper FAD-dependent oxidoreductase activity in this enzyme supports electron transfer to the mitochondrial electron transport chain via electron-transferring flavoprotein (ETF), linking fatty acid catabolism directly to respiratory chain efficiency. In C. elegans, disruption of mitochondrial fatty acid oxidation genes generally shortens lifespan, suggesting the normal function of acdh-13 is pro-longevity.
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 assumes that disruption of mitochondrial fatty acid oxidation genes generally shortens lifespan in C. elegans, leading it to classify acdh-13 as pro_longevity. However, the ground truth indicates acdh-13 is anti_longevity, meaning its normal function actually reduces lifespan (i.e., loss of acdh-13 extends lifespan). This is consistent with findings in C. elegans where reduced mitochondrial fatty acid oxidation or altered lipid metabolism can actually extend lifespan, contrary to the model's assumption. The model's mechanistic reasoning about ACAD9/Complex I assembly is speculative and not well-supported for this specific C. elegans gene. The model had moderate confidence (0.62) but was still clearly wrong in both the prediction and the underlying reasoning about the direction of effect.
Raw API responses
solver
{
"reasoning": "acdh-13 encodes a mitochondrial acyl-CoA dehydrogenase (ortholog of human ACAD9), which catalyzes the first step of mitochondrial fatty acid β-oxidation by introducing a trans-double bond into acyl-CoA substrates using FAD as a cofactor. Efficient β-oxidation is essential for maintaining mitochondrial energy homeostasis and lipid metabolism, both of which are critical determinants of lifespan in C. elegans. ACAD9 in particular is also known to function as an assembly factor for mitochondrial respiratory chain Complex I; loss of Complex I assembly impairs oxidative phosphorylation and increases ROS production, hallmarks of mitochondrial dysfunction associated with accelerated aging. Proper FAD-dependent oxidoreductase activity in this enzyme supports electron transfer to the mitochondrial electron transport chain via electron-transferring flavoprotein (ETF), linking fatty acid catabolism directly to respiratory chain efficiency. In C. elegans, disruption of mitochondrial fatty acid oxidation genes generally shortens lifespan, suggesting the normal function of acdh-13 is pro-longevity.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial fatty acid beta-oxidation",
"Complex I assembly / oxidative phosphorylation",
"FAD-dependent electron transfer via ETF"
],
"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 assumes that disruption of mitochondrial fatty acid oxidation genes generally shortens lifespan in C. elegans, leading it to classify acdh-13 as pro_longevity. However, the ground truth indicates acdh-13 is anti_longevity, meaning its normal function actually reduces lifespan (i.e., loss of acdh-13 extends lifespan). This is consistent with findings in C. elegans where reduced mitochondrial fatty acid oxidation or altered lipid metabolism can actually extend lifespan, contrary to the model's assumption. The model's mechanistic reasoning about ACAD9/Complex I assembly is speculative and not well-supported for this specific C. elegans gene. The model had moderate confidence (0.62) but was still clearly wrong in both the prediction and the underlying reasoning about the direction of effect.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}