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eif-3.B

C. elegans

Eukaryotic translation initiation factor 3 subunit B

What the model saw

Gene: eif-3.B
Organism: Caenorhabditis elegans
Known functions: Eukaryotic translation initiation factor 3 subunit B. RNA binding. translation initiation factor activity. translation initiation factor binding.
View unredacted entry
Eukaryotic translation initiation factor 3 subunit B. RNA binding. translation initiation factor activity. translation initiation factor binding.

Solver output

Predicted influence
Pro-longevity
Confidence
72%
Mechanism
Deregulated nutrient sensing
Reasoning

eif-3.B encodes subunit B of the eukaryotic translation initiation factor 3 (eIF3) complex, a core regulator of cap-dependent translation initiation. In C. elegans, global translation rate is tightly coupled to nutrient-sensing pathways, particularly TOR (mTORC1) signaling, which phosphorylates downstream effectors to upregulate eIF3-dependent ribosome recruitment. Paradoxically, partial reduction-of-function of eIF3 subunits—including eif-3.B—has been shown to reduce overall translational output, mimicking the longevity-promoting effects of TOR inhibition or dietary restriction. Lowering translation initiation via eIF3 subunit knockdown reduces proteotoxic burden and energy expenditure, thereby extending lifespan in C. elegans. This places eif-3.B in the context of deregulated nutrient sensing, where its normal (full) activity supports high translation rates that are associated with shorter lifespan, but its reduction is pro-longevity.

Key pathways
mTORC1/TOR signaling and translational controlcap-dependent translation initiation (eIF3 complex)dietary restriction mimicry via reduced global translation
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
Incorrect
Mechanism
Incorrect
Reasoning quality
2/5
Failure mode
Confident wrong
Notes

The model predicted "pro_longevity" but the ground truth is "anti_longevity." The model's reasoning is internally confused: it correctly notes that eif-3.B knockdown reduces translation and can extend lifespan, but then labels the gene itself as "pro_longevity" — which would imply that the gene's normal activity promotes longevity. The ground truth classification of "anti_longevity" is consistent with the idea that eif-3.B (in its normal/active state) promotes aging/shortens lifespan, and its reduction extends lifespan. The model essentially reasoned toward the correct mechanistic picture (reduction of eif-3.B extends lifespan) but then assigned the wrong label — calling the gene "pro_longevity" when it should be "anti_longevity." The confidence of 0.72 is also inappropriately high given the confusion in the reasoning. The mechanism class "deregulated_nutrient_sensing" is a partial fit but not the most precise framing.

Raw API responses

solver

{
  "reasoning": "eif-3.B encodes subunit B of the eukaryotic translation initiation factor 3 (eIF3) complex, a core regulator of cap-dependent translation initiation. In C. elegans, global translation rate is tightly coupled to nutrient-sensing pathways, particularly TOR (mTORC1) signaling, which phosphorylates downstream effectors to upregulate eIF3-dependent ribosome recruitment. Paradoxically, partial reduction-of-function of eIF3 subunits—including eif-3.B—has been shown to reduce overall translational output, mimicking the longevity-promoting effects of TOR inhibition or dietary restriction. Lowering translation initiation via eIF3 subunit knockdown reduces proteotoxic burden and energy expenditure, thereby extending lifespan in C. elegans. This places eif-3.B in the context of deregulated nutrient sensing, where its normal (full) activity supports high translation rates that are associated with shorter lifespan, but its reduction is pro-longevity.",
  "confidence": 0.72,
  "key_pathways": [
    "mTORC1/TOR signaling and translational control",
    "cap-dependent translation initiation (eIF3 complex)",
    "dietary restriction mimicry via reduced global translation"
  ],
  "mechanism_class": "deregulated_nutrient_sensing",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" The model's reasoning is internally confused: it correctly notes that eif-3.B knockdown reduces translation and can extend lifespan, but then labels the gene itself as \"pro_longevity\" — which would imply that the gene's normal activity promotes longevity. The ground truth classification of \"anti_longevity\" is consistent with the idea that eif-3.B (in its normal/active state) promotes aging/shortens lifespan, and its reduction extends lifespan. The model essentially reasoned toward the correct mechanistic picture (reduction of eif-3.B extends lifespan) but then assigned the wrong label — calling the gene \"pro_longevity\" when it should be \"anti_longevity.\" The confidence of 0.72 is also inappropriately high given the confusion in the reasoning. The mechanism class \"deregulated_nutrient_sensing\" is a partial fit but not the most precise framing.",
  "failure_mode": "confident_wrong",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 2,
  "ground_truth_questionable": false
}