let-23
C. elegans
Receptor tyrosine-protein kinase let-23;receptor protein-tyrosine kinase
What the model saw
Gene: let-23 Organism: Caenorhabditis elegans Known functions: Receptor tyrosine-protein kinase let-23;receptor protein-tyrosine kinase. ATP binding. epidermal growth factor receptor activity. lipid binding. molecular function activator activity. protein kinase activity. protein tyrosine kinase activity. transmembrane receptor protein tyrosine kinase activity.
View unredacted entry
Receptor tyrosine-protein kinase let-23;receptor protein-tyrosine kinase. ATP binding. epidermal growth factor receptor activity. lipid binding. molecular function activator activity. protein kinase activity. protein tyrosine kinase activity. transmembrane receptor protein tyrosine kinase activity.
Solver output
let-23 encodes the C. elegans EGF receptor (EGFR) ortholog, a receptor tyrosine kinase that activates the RAS/MAPK signaling cascade downstream of EGF ligand binding. In C. elegans, receptor tyrosine kinase signaling — including through the insulin/IGF-1 receptor DAF-2 and related RTKs — promotes growth and reproduction at the expense of longevity. Activation of let-23/EGFR drives RAS-ERK (LET-60/MPK-1) signaling, which antagonizes stress resistance and somatic maintenance programs. Reduced RTK/RAS/MAPK signaling in C. elegans is generally associated with extended lifespan, paralleling the well-established pro-aging role of hyperactive growth factor receptor signaling. Furthermore, EGFR-class RTKs share mechanistic overlap with the insulin/IGF-1 pathway in promoting anabolic, pro-growth states that shorten lifespan by suppressing DAF-16/FOXO-dependent longevity programs.
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 with 0.82 confidence, but the ground truth is pro_longevity. The model's reasoning incorrectly analogized let-23/EGFR to the insulin/IGF-1 receptor DAF-2, assuming that RTK signaling generally promotes aging. However, let-23 in C. elegans is actually pro-longevity — loss-of-function mutations in let-23 reduce lifespan. The mechanistic reasoning is flawed: while DAF-2 (insulin/IGF-1 receptor) is anti-longevity, let-23 (EGFR) plays a different role in C. elegans longevity. The model conflated two distinct RTK pathways with opposite effects on lifespan. The model was confidently wrong in both the direction of effect and the mechanistic explanation.
Raw API responses
solver
{
"reasoning": "let-23 encodes the C. elegans EGF receptor (EGFR) ortholog, a receptor tyrosine kinase that activates the RAS/MAPK signaling cascade downstream of EGF ligand binding. In C. elegans, receptor tyrosine kinase signaling — including through the insulin/IGF-1 receptor DAF-2 and related RTKs — promotes growth and reproduction at the expense of longevity. Activation of let-23/EGFR drives RAS-ERK (LET-60/MPK-1) signaling, which antagonizes stress resistance and somatic maintenance programs. Reduced RTK/RAS/MAPK signaling in C. elegans is generally associated with extended lifespan, paralleling the well-established pro-aging role of hyperactive growth factor receptor signaling. Furthermore, EGFR-class RTKs share mechanistic overlap with the insulin/IGF-1 pathway in promoting anabolic, pro-growth states that shorten lifespan by suppressing DAF-16/FOXO-dependent longevity programs.",
"confidence": 0.82,
"key_pathways": [
"EGF receptor / RAS-MAPK signaling (LET-23 → LET-60 → MPK-1)",
"Insulin/IGF-1-like RTK longevity axis (DAF-2/DAF-16 parallel)",
"Receptor tyrosine kinase-mediated growth vs. somatic maintenance trade-off"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity with 0.82 confidence, but the ground truth is pro_longevity. The model's reasoning incorrectly analogized let-23/EGFR to the insulin/IGF-1 receptor DAF-2, assuming that RTK signaling generally promotes aging. However, let-23 in C. elegans is actually pro-longevity — loss-of-function mutations in let-23 reduce lifespan. The mechanistic reasoning is flawed: while DAF-2 (insulin/IGF-1 receptor) is anti-longevity, let-23 (EGFR) plays a different role in C. elegans longevity. The model conflated two distinct RTK pathways with opposite effects on lifespan. The model was confidently wrong in both the direction of effect and the mechanistic explanation.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}