ALD4
S. cerevisiae
aldehyde dehydrogenase (NADP(+)) ALD4
What the model saw
Gene: ALD4 Organism: Saccharomyces cerevisiae Known functions: aldehyde dehydrogenase (NADP(+)) ALD4. acetaldehyde dehydrogenase (NADP+) activity. aldehyde dehydrogenase (NAD+) activity. aldehyde dehydrogenase (NADP+) activity. aldehyde dehydrogenase [NAD(P)+] activity. oxidoreductase activity.
View unredacted entry
aldehyde dehydrogenase (NADP(+)) ALD4. acetaldehyde dehydrogenase (NADP+) activity. aldehyde dehydrogenase (NAD+) activity. aldehyde dehydrogenase (NADP+) activity. aldehyde dehydrogenase [NAD(P)+] activity. oxidoreductase activity.
Solver output
ALD4 encodes the major mitochondrial aldehyde dehydrogenase in S. cerevisiae, catalyzing the NAD(P)+-dependent oxidation of acetaldehyde to acetate. This reaction serves two critical pro-longevity functions: first, it detoxifies acetaldehyde, a reactive and genotoxic carbonyl species that causes protein and DNA damage; second, it channels carbon flux into acetyl-CoA via acetate, supporting mitochondrial energy metabolism. By reducing acetaldehyde accumulation, ALD4 limits oxidative and carbonyl stress, which are key drivers of mitochondrial dysfunction and cellular damage during aging. Mitochondrial aldehyde dehydrogenase activity is broadly conserved as a longevity-promoting function across eukaryotes, and loss of ALD4 in yeast impairs respiratory growth and increases oxidative stress markers. The NADP+ cofactor usage also generates NADPH, supporting antioxidant defenses.
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 with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — ALD4 does encode a mitochondrial aldehyde dehydrogenase and does detoxify acetaldehyde — but the conclusion is wrong. In yeast replicative or chronological aging studies, ALD4 deletion or overexpression experiments apparently show it has an anti-longevity effect, meaning the gene promotes aging rather than extending lifespan. The model's mechanistic narrative (detoxification, NADPH generation, acetyl-CoA flux) is reasonable biochemistry but leads to the wrong prediction. The model was moderately confident (0.72) in an incorrect answer, making this a confident_wrong failure. The reasoning quality is moderate — the biochemistry described is real but the conclusion drawn from it is incorrect.
Raw API responses
solver
{
"reasoning": "ALD4 encodes the major mitochondrial aldehyde dehydrogenase in S. cerevisiae, catalyzing the NAD(P)+-dependent oxidation of acetaldehyde to acetate. This reaction serves two critical pro-longevity functions: first, it detoxifies acetaldehyde, a reactive and genotoxic carbonyl species that causes protein and DNA damage; second, it channels carbon flux into acetyl-CoA via acetate, supporting mitochondrial energy metabolism. By reducing acetaldehyde accumulation, ALD4 limits oxidative and carbonyl stress, which are key drivers of mitochondrial dysfunction and cellular damage during aging. Mitochondrial aldehyde dehydrogenase activity is broadly conserved as a longevity-promoting function across eukaryotes, and loss of ALD4 in yeast impairs respiratory growth and increases oxidative stress markers. The NADP+ cofactor usage also generates NADPH, supporting antioxidant defenses.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial acetaldehyde detoxification",
"NAD(P)H redox homeostasis",
"acetate/acetyl-CoA metabolic flux"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — ALD4 does encode a mitochondrial aldehyde dehydrogenase and does detoxify acetaldehyde — but the conclusion is wrong. In yeast replicative or chronological aging studies, ALD4 deletion or overexpression experiments apparently show it has an anti-longevity effect, meaning the gene promotes aging rather than extending lifespan. The model's mechanistic narrative (detoxification, NADPH generation, acetyl-CoA flux) is reasonable biochemistry but leads to the wrong prediction. The model was moderately confident (0.72) in an incorrect answer, making this a confident_wrong failure. The reasoning quality is moderate — the biochemistry described is real but the conclusion drawn from it is incorrect.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}