eif-2beta
C. elegans
Eukaryotic translation initiation factor 2 subunit 2
What the model saw
Gene: eif-2beta Organism: Caenorhabditis elegans Known functions: Eukaryotic translation initiation factor 2 subunit 2. mRNA binding. translation initiation factor activity. translation initiation factor binding.
View unredacted entry
Eukaryotic translation initiation factor 2 subunit 2. mRNA binding. translation initiation factor activity. translation initiation factor binding.
Solver output
eif-2beta encodes the beta subunit of eukaryotic initiation factor 2 (eIF2), which is a central component of the translation initiation machinery. eIF2 loads the initiator Met-tRNA onto the 40S ribosomal subunit and is a key node integrating nutrient-sensing and stress signals into global translational output. Reduced global translation — achieved through phosphorylation of eIF2α (the alpha subunit) or partial loss of eIF2 complex activity — is a well-established pro-longevity mechanism in C. elegans and other organisms, as it mimics dietary restriction and activates the integrated stress response (ISR). Conversely, the normal (wild-type) function of eIF2β is to promote robust translation initiation, thereby sustaining high rates of protein synthesis that are associated with shorter lifespan. Genetic reduction of eIF2 subunits in C. elegans has been shown to extend lifespan, consistent with the idea that the normal pro-translational activity of eIF2β opposes longevity. This places eIF2β in the deregulated nutrient-sensing hallmark, as mTOR/translation axis activity is a primary readout of nutrient status and a key determinant of lifespan.
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 predicted anti_longevity for eif-2beta. The mechanistic reasoning is sound: eIF2β promotes translation initiation, and reducing translation is pro-longevity in C. elegans, so the wild-type function of eIF2β opposes longevity (anti_longevity). The mechanism class of "deregulated_nutrient_sensing" is reasonable given the connection between translation and nutrient sensing/mTOR pathways, though one could argue "altered translation" would be more precise. The reasoning correctly identifies that loss of eIF2 subunit activity extends lifespan, making the normal function anti-longevity. Confidence of 0.72 is appropriate given the indirect nature of the evidence cited.
Raw API responses
solver
{
"reasoning": "eif-2beta encodes the beta subunit of eukaryotic initiation factor 2 (eIF2), which is a central component of the translation initiation machinery. eIF2 loads the initiator Met-tRNA onto the 40S ribosomal subunit and is a key node integrating nutrient-sensing and stress signals into global translational output. Reduced global translation — achieved through phosphorylation of eIF2α (the alpha subunit) or partial loss of eIF2 complex activity — is a well-established pro-longevity mechanism in C. elegans and other organisms, as it mimics dietary restriction and activates the integrated stress response (ISR). Conversely, the normal (wild-type) function of eIF2β is to promote robust translation initiation, thereby sustaining high rates of protein synthesis that are associated with shorter lifespan. Genetic reduction of eIF2 subunits in C. elegans has been shown to extend lifespan, consistent with the idea that the normal pro-translational activity of eIF2β opposes longevity. This places eIF2β in the deregulated nutrient-sensing hallmark, as mTOR/translation axis activity is a primary readout of nutrient status and a key determinant of lifespan.",
"confidence": 0.72,
"key_pathways": [
"eIF2 translation initiation complex",
"integrated stress response (ISR) / eIF2alpha phosphorylation",
"mTOR-translation axis / dietary restriction mimicry"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for eif-2beta. The mechanistic reasoning is sound: eIF2β promotes translation initiation, and reducing translation is pro-longevity in C. elegans, so the wild-type function of eIF2β opposes longevity (anti_longevity). The mechanism class of \"deregulated_nutrient_sensing\" is reasonable given the connection between translation and nutrient sensing/mTOR pathways, though one could argue \"altered translation\" would be more precise. The reasoning correctly identifies that loss of eIF2 subunit activity extends lifespan, making the normal function anti-longevity. Confidence of 0.72 is appropriate given the indirect nature of the evidence cited.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}