AhcyL1
D. melanogaster
Adenosylhomocysteinase like 1
What the model saw
Gene: AhcyL1 Organism: Drosophila melanogaster Known functions: Adenosylhomocysteinase like 1. adenosylhomocysteinase like 1. adenosylhomocysteinase activity.
View unredacted entry
Adenosylhomocysteinase like 1. adenosylhomocysteinase like 1. adenosylhomocysteinase activity.
Solver output
AhcyL1 encodes an adenosylhomocysteinase (AHCY)-like enzyme that hydrolyzes S-adenosylhomocysteine (SAH) into adenosine and homocysteine. SAH is a potent product-inhibitor of S-adenosylmethionine (SAM)-dependent methyltransferases; by clearing SAH, AHCY activity is essential for maintaining the SAM/SAH ratio and sustaining methylation reactions. Proper methylation capacity—including histone and DNA methylation—is critical for epigenetic regulation and gene silencing. Loss of AHCY function leads to SAH accumulation, global hypomethylation, and dysregulated epigenetic states associated with accelerated aging phenotypes. Additionally, one-carbon/methionine cycle flux is tightly linked to longevity in multiple model organisms, including Drosophila, where methionine restriction extends lifespan. Thus, normal AhcyL1 function supports the methylation capacity needed for healthy epigenetic maintenance and is predicted to be 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 about AHCY function and SAH hydrolysis is biochemically sound in general terms, but it drew the wrong conclusion about the longevity direction. The model argued that AhcyL1 supports methylation capacity and is therefore pro-longevity, but the ground truth indicates it is anti-longevity. This suggests that AhcyL1 activity (clearing SAH and maintaining methylation) actually promotes aging rather than extending lifespan in Drosophila — possibly because excessive methylation activity or methionine cycle flux is detrimental to longevity, consistent with findings that methionine restriction (which would reduce SAM availability and methylation) extends lifespan. The model's reasoning actually contains the seeds of the correct answer (methionine restriction extends lifespan) but failed to follow through to the correct conclusion: if methionine restriction is beneficial, then maintaining high methylation capacity via AhcyL1 would be anti-longevity. The model had moderate confidence (0.65) but still got the direction wrong.
Raw API responses
solver
{
"reasoning": "AhcyL1 encodes an adenosylhomocysteinase (AHCY)-like enzyme that hydrolyzes S-adenosylhomocysteine (SAH) into adenosine and homocysteine. SAH is a potent product-inhibitor of S-adenosylmethionine (SAM)-dependent methyltransferases; by clearing SAH, AHCY activity is essential for maintaining the SAM/SAH ratio and sustaining methylation reactions. Proper methylation capacity—including histone and DNA methylation—is critical for epigenetic regulation and gene silencing. Loss of AHCY function leads to SAH accumulation, global hypomethylation, and dysregulated epigenetic states associated with accelerated aging phenotypes. Additionally, one-carbon/methionine cycle flux is tightly linked to longevity in multiple model organisms, including Drosophila, where methionine restriction extends lifespan. Thus, normal AhcyL1 function supports the methylation capacity needed for healthy epigenetic maintenance and is predicted to be pro-longevity.",
"confidence": 0.65,
"key_pathways": [
"S-adenosylhomocysteine hydrolysis / methionine cycle",
"SAM-dependent methyltransferase regulation",
"one-carbon metabolism and epigenetic maintenance"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about AHCY function and SAH hydrolysis is biochemically sound in general terms, but it drew the wrong conclusion about the longevity direction. The model argued that AhcyL1 supports methylation capacity and is therefore pro-longevity, but the ground truth indicates it is anti-longevity. This suggests that AhcyL1 activity (clearing SAH and maintaining methylation) actually promotes aging rather than extending lifespan in Drosophila — possibly because excessive methylation activity or methionine cycle flux is detrimental to longevity, consistent with findings that methionine restriction (which would reduce SAM availability and methylation) extends lifespan. The model's reasoning actually contains the seeds of the correct answer (methionine restriction extends lifespan) but failed to follow through to the correct conclusion: if methionine restriction is beneficial, then maintaining high methylation capacity via AhcyL1 would be anti-longevity. The model had moderate confidence (0.65) but still got the direction wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}