egl-8

C. elegans

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase;1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta egl-8;Phosphoinositide phospholipase C

What the model saw

Gene: egl-8
Organism: Caenorhabditis elegans
Known functions: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase;1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta egl-8;Phosphoinositide phospholipase C. calcium ion binding. phosphatidylinositol-4,5-bisphosphate phospholipase C activity. phosphoric diester hydrolase activity.

View unredacted entry

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase;1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta egl-8;Phosphoinositide phospholipase C. calcium ion binding. phosphatidylinositol-4,5-bisphosphate phospholipase C activity. phosphoric diester hydrolase activity.

Solver output

Predicted influence

Anti-longevity

Confidence

68%

Mechanism

Deregulated nutrient sensing

Reasoning

EGL-8 is the C. elegans phospholipase C-beta (PLCβ), which hydrolyzes phosphatidylinositol-4,5-bisphosphate (PIP2) to generate diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP3). DAG activates protein kinase C (PKC), while IP3 triggers intracellular calcium release. In C. elegans, this PLCβ signaling axis operates downstream of Gαq (EGL-30), a pathway known to antagonize longevity by promoting neuronal activity and counteracting the pro-longevity effects of reduced insulin/IGF-1 signaling and DAF-16/FOXO. Elevated Gαq-PLCβ-DAG signaling shortens lifespan, while loss-of-function in this pathway (including egl-8 mutants) extends lifespan, placing EGL-8's normal function in opposition to longevity. The calcium-dependent signaling downstream of EGL-8 also intersects with mitochondrial and metabolic regulation in ways that tend to promote aging rather than oppose it.

Key pathways

Gαq-PLCβ (EGL-30/EGL-8) signalingDAG/PKC signalingIP3-mediated calcium release

Longevity influence

Anti-longevity

Lifespan effect

Increase

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

Answer

✓Correct

Mechanism

✓Correct

Reasoning quality

5/5

Failure mode

Correct

Notes

The model correctly predicted egl-8 as anti_longevity. The mechanistic reasoning is accurate and well-detailed: EGL-8 is PLCβ acting downstream of Gαq (EGL-30), generating DAG and IP3, promoting neuronal activity and opposing pro-longevity pathways. Loss-of-function of egl-8 extends lifespan in C. elegans, making it anti-longevity in its normal function. The mechanism class "deregulated_nutrient_sensing" is a slight oversimplification (it's more of a neuromodulatory/Gαq signaling pathway), but the detailed reasoning correctly identifies the actual pathway. Confidence of 0.68 is appropriately calibrated.

Raw API responses

solver

{
  "reasoning": "EGL-8 is the C. elegans phospholipase C-beta (PLCβ), which hydrolyzes phosphatidylinositol-4,5-bisphosphate (PIP2) to generate diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP3). DAG activates protein kinase C (PKC), while IP3 triggers intracellular calcium release. In C. elegans, this PLCβ signaling axis operates downstream of Gαq (EGL-30), a pathway known to antagonize longevity by promoting neuronal activity and counteracting the pro-longevity effects of reduced insulin/IGF-1 signaling and DAF-16/FOXO. Elevated Gαq-PLCβ-DAG signaling shortens lifespan, while loss-of-function in this pathway (including egl-8 mutants) extends lifespan, placing EGL-8's normal function in opposition to longevity. The calcium-dependent signaling downstream of EGL-8 also intersects with mitochondrial and metabolic regulation in ways that tend to promote aging rather than oppose it.",
  "confidence": 0.68,
  "key_pathways": [
    "Gαq-PLCβ (EGL-30/EGL-8) signaling",
    "DAG/PKC signaling",
    "IP3-mediated calcium release"
  ],
  "mechanism_class": "deregulated_nutrient_sensing",
  "longevity_influence": "anti_longevity"
}

advisor

{
  "notes": "The model correctly predicted egl-8 as anti_longevity. The mechanistic reasoning is accurate and well-detailed: EGL-8 is PLCβ acting downstream of Gαq (EGL-30), generating DAG and IP3, promoting neuronal activity and opposing pro-longevity pathways. Loss-of-function of egl-8 extends lifespan in C. elegans, making it anti-longevity in its normal function. The mechanism class \"deregulated_nutrient_sensing\" is a slight oversimplification (it's more of a neuromodulatory/Gαq signaling pathway), but the detailed reasoning correctly identifies the actual pathway. Confidence of 0.68 is appropriately calibrated.",
  "failure_mode": "correct",
  "answer_correct": true,
  "mechanism_correct": true,
  "reasoning_quality": 5,
  "ground_truth_questionable": false
}