Pka-C1

D. melanogaster

Protein kinase, cAMP-dependent, catalytic subunit 1

What the model saw

Gene: Pka-C1
Organism: Drosophila melanogaster
Known functions: Protein kinase, cAMP-dependent, catalytic subunit 1. protein kinase, cAMP-dependent, catalytic subunit 1. ATP binding. cAMP-dependent protein kinase activity. cyclic nucleotide-dependent protein kinase activity. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.

View unredacted entry

Protein kinase, cAMP-dependent, catalytic subunit 1. protein kinase, cAMP-dependent, catalytic subunit 1. ATP binding. cAMP-dependent protein kinase activity. cyclic nucleotide-dependent protein kinase activity. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.

Solver output

Predicted influence

Anti-longevity

Confidence

72%

Mechanism

Deregulated nutrient sensing

Reasoning

Pka-C1 encodes the catalytic subunit of cAMP-dependent protein kinase A (PKA), a central effector of the cAMP/PKA signaling axis in Drosophila. PKA activity is a key downstream mediator of nutrient and energy sensing pathways; elevated PKA signaling promotes anabolic processes and suppresses stress-response programs, paralleling the pro-aging effects of hyperactive insulin/IGF-1 and TOR signaling. In multiple model organisms, reduced PKA activity or cAMP signaling extends lifespan, while elevated PKA activity shortens it by antagonizing FOXO/dFOXO transcription factors and dampening autophagy. Additionally, PKA phosphorylates and inhibits components of the AMPK pathway, further tipping the balance toward nutrient-sensing deregulation associated with accelerated aging. Thus, the normal (active) function of Pka-C1 is expected to oppose longevity.

Key pathways

cAMP/PKA signalingFOXO transcription factor regulationAMPK/nutrient sensing

Longevity influence

Pro-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

✗Incorrect

Mechanism

✗Incorrect

Reasoning quality

2/5

Failure mode

Confident wrong

Notes

The model predicted anti_longevity with 0.72 confidence, but the ground truth is pro_longevity. The model's reasoning follows a plausible but incorrect narrative — it assumed that PKA activity is pro-aging by analogy with hyperactive insulin/IGF-1 and TOR signaling, and by citing FOXO inhibition and AMPK antagonism. However, in Drosophila, Pka-C1 is actually pro-longevity, suggesting that PKA signaling in this context promotes longevity rather than opposing it. The model's mechanistic reasoning is also incorrect — it conflates PKA's role across organisms without accounting for Drosophila-specific findings. The model was fairly confident (0.72) in the wrong direction, making this a clear confident_wrong failure.

Raw API responses

solver

{
  "reasoning": "Pka-C1 encodes the catalytic subunit of cAMP-dependent protein kinase A (PKA), a central effector of the cAMP/PKA signaling axis in Drosophila. PKA activity is a key downstream mediator of nutrient and energy sensing pathways; elevated PKA signaling promotes anabolic processes and suppresses stress-response programs, paralleling the pro-aging effects of hyperactive insulin/IGF-1 and TOR signaling. In multiple model organisms, reduced PKA activity or cAMP signaling extends lifespan, while elevated PKA activity shortens it by antagonizing FOXO/dFOXO transcription factors and dampening autophagy. Additionally, PKA phosphorylates and inhibits components of the AMPK pathway, further tipping the balance toward nutrient-sensing deregulation associated with accelerated aging. Thus, the normal (active) function of Pka-C1 is expected to oppose longevity.",
  "confidence": 0.72,
  "key_pathways": [
    "cAMP/PKA signaling",
    "FOXO transcription factor regulation",
    "AMPK/nutrient sensing"
  ],
  "mechanism_class": "deregulated_nutrient_sensing",
  "longevity_influence": "anti_longevity"
}

advisor

{
  "notes": "The model predicted anti_longevity with 0.72 confidence, but the ground truth is pro_longevity. The model's reasoning follows a plausible but incorrect narrative — it assumed that PKA activity is pro-aging by analogy with hyperactive insulin/IGF-1 and TOR signaling, and by citing FOXO inhibition and AMPK antagonism. However, in Drosophila, Pka-C1 is actually pro-longevity, suggesting that PKA signaling in this context promotes longevity rather than opposing it. The model's mechanistic reasoning is also incorrect — it conflates PKA's role across organisms without accounting for Drosophila-specific findings. The model was fairly confident (0.72) in the wrong direction, making this a clear confident_wrong failure.",
  "failure_mode": "confident_wrong",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 2,
  "ground_truth_questionable": false
}