age-1
C. elegans
Phosphatidylinositol 3-kinase age-1
What the model saw
Gene: age-1 Organism: Caenorhabditis elegans Known functions: Phosphatidylinositol 3-kinase age-1. 1-phosphatidylinositol-3-kinase activity. 1-phosphatidylinositol-4-phosphate 3-kinase activity. kinase activity. protein binding.
View unredacted entry
Phosphatidylinositol 3-kinase age-1. 1-phosphatidylinositol-3-kinase activity. 1-phosphatidylinositol-4-phosphate 3-kinase activity. kinase activity. protein binding.
Solver output
age-1 encodes the C. elegans ortholog of the p110 catalytic subunit of phosphatidylinositol 3-kinase (PI3K), which phosphorylates PIP2 to generate PIP3. PIP3 recruits and activates PDK-1 and AKT-1/AKT-2, which in turn phosphorylate and cytoplasmic-sequester the FOXO transcription factor DAF-16. DAF-16 nuclear exclusion suppresses expression of stress-resistance, detoxification, and longevity-promoting genes. Loss-of-function mutations in age-1 are among the first and most robust lifespan-extending interventions identified in C. elegans, dramatically extending lifespan by allowing DAF-16 nuclear translocation. Thus, the normal (wild-type) function of age-1 — activating the insulin/IGF-1 signaling (IIS) axis — opposes longevity by suppressing DAF-16-dependent pro-longevity transcription.
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 correctly identifies age-1 as anti_longevity with very high confidence (0.98). The mechanistic reasoning is exemplary: it accurately describes age-1 as the PI3K catalytic subunit that phosphorylates PIP2→PIP3, activates PDK-1/AKT, sequesters DAF-16/FOXO in the cytoplasm, and explains why loss-of-function extends lifespan. The pathway classification (IIS, PI3K-PIP3-AKT, DAF-16/FOXO) is fully correct. This is a well-known C. elegans aging gene and the model demonstrates deep, accurate knowledge of the underlying biology.
Raw API responses
solver
{
"reasoning": "age-1 encodes the C. elegans ortholog of the p110 catalytic subunit of phosphatidylinositol 3-kinase (PI3K), which phosphorylates PIP2 to generate PIP3. PIP3 recruits and activates PDK-1 and AKT-1/AKT-2, which in turn phosphorylate and cytoplasmic-sequester the FOXO transcription factor DAF-16. DAF-16 nuclear exclusion suppresses expression of stress-resistance, detoxification, and longevity-promoting genes. Loss-of-function mutations in age-1 are among the first and most robust lifespan-extending interventions identified in C. elegans, dramatically extending lifespan by allowing DAF-16 nuclear translocation. Thus, the normal (wild-type) function of age-1 — activating the insulin/IGF-1 signaling (IIS) axis — opposes longevity by suppressing DAF-16-dependent pro-longevity transcription.",
"confidence": 0.98,
"key_pathways": [
"Insulin/IGF-1 signaling (IIS) pathway",
"PI3K-PIP3-AKT signaling",
"DAF-16/FOXO transcription factor regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identifies age-1 as anti_longevity with very high confidence (0.98). The mechanistic reasoning is exemplary: it accurately describes age-1 as the PI3K catalytic subunit that phosphorylates PIP2→PIP3, activates PDK-1/AKT, sequesters DAF-16/FOXO in the cytoplasm, and explains why loss-of-function extends lifespan. The pathway classification (IIS, PI3K-PIP3-AKT, DAF-16/FOXO) is fully correct. This is a well-known C. elegans aging gene and the model demonstrates deep, accurate knowledge of the underlying biology.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}