aat-8
C. elegans
Amino acid transporter
What the model saw
Gene: aat-8 Organism: Caenorhabditis elegans Known functions: Amino acid transporter. L-amino acid transmembrane transporter activity. transmembrane transporter activity.
View unredacted entry
Amino acid transporter. L-amino acid transmembrane transporter activity. transmembrane transporter activity.
Solver output
aat-8 encodes an L-amino acid transmembrane transporter in C. elegans, functioning to import amino acids across cellular membranes. Amino acid transporter activity directly feeds into nutrient-sensing pathways, particularly the mTORC1 (TORC1) pathway, which is activated by intracellular amino acid availability. In C. elegans, reduced amino acid import or signaling through TORC1 is associated with lifespan extension, as TORC1 inhibition mimics dietary restriction. If aat-8 promotes amino acid uptake and thereby sustains TORC1 activity, its loss would reduce nutrient sensing and extend lifespan, making its normal function anti-longevity. However, amino acid transporters can also be essential for maintaining proteostasis and cellular homeostasis, which would be pro-longevity. Given the direct link between amino acid transporter activity and TORC1 nutrient sensing in C. elegans, and evidence that amino acid transporter knockdowns can extend lifespan by limiting mTOR activation, the normal function of aat-8 is tentatively pro-longevity through supporting cellular amino acid homeostasis, though the net effect depends on which tissues and pathways predominate.
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 - it correctly identifies that amino acid transporters feed into TORC1 signaling and that loss of such transporters could extend lifespan (making the gene anti-longevity), but then reverses course and concludes pro_longevity based on a weaker argument about proteostasis. The model even explicitly states "its normal function anti-longevity" in one sentence before contradicting itself. The mechanistic reasoning that led to the correct conclusion (TORC1 activation via amino acid import = anti-longevity) was abandoned in favor of an incorrect final answer. The confidence of 0.52 reflects appropriate uncertainty, but the final answer is still wrong.
Raw API responses
solver
{
"reasoning": "aat-8 encodes an L-amino acid transmembrane transporter in C. elegans, functioning to import amino acids across cellular membranes. Amino acid transporter activity directly feeds into nutrient-sensing pathways, particularly the mTORC1 (TORC1) pathway, which is activated by intracellular amino acid availability. In C. elegans, reduced amino acid import or signaling through TORC1 is associated with lifespan extension, as TORC1 inhibition mimics dietary restriction. If aat-8 promotes amino acid uptake and thereby sustains TORC1 activity, its loss would reduce nutrient sensing and extend lifespan, making its normal function anti-longevity. However, amino acid transporters can also be essential for maintaining proteostasis and cellular homeostasis, which would be pro-longevity. Given the direct link between amino acid transporter activity and TORC1 nutrient sensing in C. elegans, and evidence that amino acid transporter knockdowns can extend lifespan by limiting mTOR activation, the normal function of aat-8 is tentatively pro-longevity through supporting cellular amino acid homeostasis, though the net effect depends on which tissues and pathways predominate.",
"confidence": 0.52,
"key_pathways": [
"mTORC1/TORC1 amino acid sensing",
"dietary restriction signaling",
"L-amino acid transmembrane transport"
],
"mechanism_class": "deregulated_nutrient_sensing",
"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 - it correctly identifies that amino acid transporters feed into TORC1 signaling and that loss of such transporters could extend lifespan (making the gene anti-longevity), but then reverses course and concludes pro_longevity based on a weaker argument about proteostasis. The model even explicitly states \"its normal function anti-longevity\" in one sentence before contradicting itself. The mechanistic reasoning that led to the correct conclusion (TORC1 activation via amino acid import = anti-longevity) was abandoned in favor of an incorrect final answer. The confidence of 0.52 reflects appropriate uncertainty, but the final answer is still wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}