nars-1
C. elegans
Asparagine--tRNA ligase, cytoplasmic
What the model saw
Gene: nars-1 Organism: Caenorhabditis elegans Known functions: Asparagine--tRNA ligase, cytoplasmic. ATP binding. aminoacyl-tRNA ligase activity. asparagine-tRNA ligase activity. nucleic acid binding. nucleotide binding.
View unredacted entry
Asparagine--tRNA ligase, cytoplasmic. ATP binding. aminoacyl-tRNA ligase activity. asparagine-tRNA ligase activity. nucleic acid binding. nucleotide binding.
Solver output
nars-1 encodes the cytoplasmic asparagine-tRNA synthetase (AsnRS), which charges tRNA-Asn with asparagine, a rate-limiting step in translation elongation. Accurate and efficient aminoacylation is essential for translational fidelity and proteostasis; defects in tRNA charging lead to ribosome stalling, misincorporation, and proteotoxic stress. In C. elegans, partial loss-of-function of cytoplasmic aminoacyl-tRNA synthetases has been shown to reduce global translation rates, which mimics dietary restriction and activates longevity pathways (e.g., reduced IIS/TOR signaling). The normal function of nars-1 sustains high translational output, which is associated with faster aging, while its reduction extends lifespan—suggesting the wild-type gene is net anti-longevity. However, complete loss would be lethal, and the gene's primary role in maintaining proteostasis through accurate translation argues for a pro-longevity classification of its normal, faithful function. Balancing these considerations, the dominant paradigm in C. elegans places aminoacyl-tRNA synthetase activity on the pro-longevity side when functioning correctly to prevent mistranslation and proteotoxicity.
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 actually articulates the anti_longevity argument well (that nars-1 sustains high translational output associated with faster aging, and its reduction extends lifespan), but then reverses course and concludes pro_longevity based on the proteostasis/translational fidelity argument. The model essentially talked itself out of the correct answer. The reasoning about reduced translation mimicking dietary restriction and extending lifespan is consistent with anti_longevity classification for the wild-type gene, but the model failed to commit to this conclusion. The confidence of 0.62 is moderate but still wrong. The mechanism discussion about TOR/dietary restriction is partially relevant but the final mechanistic classification of 'loss_of_proteostasis' doesn't align well with the anti_longevity ground truth either.
Raw API responses
solver
{
"reasoning": "nars-1 encodes the cytoplasmic asparagine-tRNA synthetase (AsnRS), which charges tRNA-Asn with asparagine, a rate-limiting step in translation elongation. Accurate and efficient aminoacylation is essential for translational fidelity and proteostasis; defects in tRNA charging lead to ribosome stalling, misincorporation, and proteotoxic stress. In C. elegans, partial loss-of-function of cytoplasmic aminoacyl-tRNA synthetases has been shown to reduce global translation rates, which mimics dietary restriction and activates longevity pathways (e.g., reduced IIS/TOR signaling). The normal function of nars-1 sustains high translational output, which is associated with faster aging, while its reduction extends lifespan—suggesting the wild-type gene is net anti-longevity. However, complete loss would be lethal, and the gene's primary role in maintaining proteostasis through accurate translation argues for a pro-longevity classification of its normal, faithful function. Balancing these considerations, the dominant paradigm in C. elegans places aminoacyl-tRNA synthetase activity on the pro-longevity side when functioning correctly to prevent mistranslation and proteotoxicity.",
"confidence": 0.62,
"key_pathways": [
"aminoacyl-tRNA biosynthesis / translational fidelity",
"proteostasis network",
"TOR/dietary restriction signaling"
],
"mechanism_class": "loss_of_proteostasis",
"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 actually articulates the anti_longevity argument well (that nars-1 sustains high translational output associated with faster aging, and its reduction extends lifespan), but then reverses course and concludes pro_longevity based on the proteostasis/translational fidelity argument. The model essentially talked itself out of the correct answer. The reasoning about reduced translation mimicking dietary restriction and extending lifespan is consistent with anti_longevity classification for the wild-type gene, but the model failed to commit to this conclusion. The confidence of 0.62 is moderate but still wrong. The mechanism discussion about TOR/dietary restriction is partially relevant but the final mechanistic classification of 'loss_of_proteostasis' doesn't align well with the anti_longevity ground truth either.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}