lin-3
C. elegans
EGF-like domain-containing protein;Protein lin-3
What the model saw
Gene: lin-3 Organism: Caenorhabditis elegans Known functions: EGF-like domain-containing protein;Protein lin-3. growth factor activity. receptor ligand activity.
View unredacted entry
EGF-like domain-containing protein;Protein lin-3. growth factor activity. receptor ligand activity.
Solver output
LIN-3 is the C. elegans EGF ligand that activates the LET-23/EGFR receptor tyrosine kinase pathway. Activation of receptor tyrosine kinase signaling in C. elegans converges on RAS/MAPK and PI3K/AKT cascades, which are well-established pro-growth, pro-aging pathways. Elevated RTK-RAS-ERK signaling opposes DAF-16/FOXO nuclear activity, a key transcription factor promoting stress resistance and longevity downstream of the insulin/IGF-1 pathway. Because LIN-3 acts as a mitogenic growth factor driving proliferative and anabolic signaling, its normal function promotes somatic growth at the expense of longevity assurance mechanisms, placing it in the deregulated nutrient/growth-factor sensing hallmark. Reduction-of-function in EGF/RAS signaling components in C. elegans has been associated with lifespan extension, consistent with LIN-3 being anti-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 anti_longevity but the ground truth is pro_longevity. The model's reasoning is plausible in general terms (EGF/RAS signaling can be pro-aging in some contexts), but it misapplies this logic to lin-3 in C. elegans. In reality, lin-3 (the EGF ligand for LET-23) has been shown to promote longevity in C. elegans, likely through its role in vulval development and germline signaling rather than simply driving pro-aging anabolic signaling. The model conflates EGF/RTK signaling with insulin/IGF-1-like pro-aging effects without accounting for the specific context of lin-3's role in C. elegans lifespan. The model was fairly confident (0.72) in its wrong answer, and the mechanistic reasoning, while internally consistent, leads to the wrong conclusion.
Raw API responses
solver
{
"reasoning": "LIN-3 is the C. elegans EGF ligand that activates the LET-23/EGFR receptor tyrosine kinase pathway. Activation of receptor tyrosine kinase signaling in C. elegans converges on RAS/MAPK and PI3K/AKT cascades, which are well-established pro-growth, pro-aging pathways. Elevated RTK-RAS-ERK signaling opposes DAF-16/FOXO nuclear activity, a key transcription factor promoting stress resistance and longevity downstream of the insulin/IGF-1 pathway. Because LIN-3 acts as a mitogenic growth factor driving proliferative and anabolic signaling, its normal function promotes somatic growth at the expense of longevity assurance mechanisms, placing it in the deregulated nutrient/growth-factor sensing hallmark. Reduction-of-function in EGF/RAS signaling components in C. elegans has been associated with lifespan extension, consistent with LIN-3 being anti-longevity.",
"confidence": 0.72,
"key_pathways": [
"LIN-3/LET-23 EGFR signaling",
"RAS/MAPK cascade",
"PI3K/AKT-DAF-16/FOXO axis"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity but the ground truth is pro_longevity. The model's reasoning is plausible in general terms (EGF/RAS signaling can be pro-aging in some contexts), but it misapplies this logic to lin-3 in C. elegans. In reality, lin-3 (the EGF ligand for LET-23) has been shown to promote longevity in C. elegans, likely through its role in vulval development and germline signaling rather than simply driving pro-aging anabolic signaling. The model conflates EGF/RTK signaling with insulin/IGF-1-like pro-aging effects without accounting for the specific context of lin-3's role in C. elegans lifespan. The model was fairly confident (0.72) in its wrong answer, and the mechanistic reasoning, while internally consistent, leads to the wrong conclusion.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}