gpi-1
C. elegans
Glucose-6-phosphate isomerase
What the model saw
Gene: gpi-1 Organism: Caenorhabditis elegans Known functions: Glucose-6-phosphate isomerase. carbohydrate derivative binding. glucose-6-phosphate isomerase activity. isomerase activity. monosaccharide binding.
View unredacted entry
Glucose-6-phosphate isomerase. carbohydrate derivative binding. glucose-6-phosphate isomerase activity. isomerase activity. monosaccharide binding.
Solver output
GPI-1 encodes glucose-6-phosphate isomerase, which catalyzes the interconversion of glucose-6-phosphate and fructose-6-phosphate, a key step in glycolysis. By promoting glycolytic flux, GPI-1 supports glucose catabolism and energy production through the glycolytic pathway rather than directing glucose-6-phosphate into the pentose phosphate pathway (which generates NADPH and supports oxidative stress defense). In C. elegans, enhanced glycolysis is associated with reduced lifespan, while reduced glycolytic activity (e.g., via inhibition of downstream glycolytic enzymes) has been shown to extend lifespan through mechanisms involving AMPK activation and DAF-16/FOXO signaling. Thus, the normal pro-glycolytic function of gpi-1 is expected to promote glucose consumption and suppress longevity-associated metabolic reprogramming, placing it in the deregulated nutrient-sensing hallmark of aging.
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 gpi-1. The mechanistic reasoning is sound and well-grounded: GPI-1 promotes glycolytic flux, and in C. elegans, enhanced glycolysis is associated with reduced lifespan, while inhibiting glycolytic enzymes extends lifespan. The model correctly identifies the connection to AMPK and DAF-16/FOXO signaling. The pentose phosphate pathway diversion argument is also reasonable. Confidence of 0.65 is appropriately calibrated. Minor deduction: the reasoning is somewhat general/inferential rather than citing specific gpi-1 experimental data, but the logic is coherent and correct.
Raw API responses
solver
{
"reasoning": "GPI-1 encodes glucose-6-phosphate isomerase, which catalyzes the interconversion of glucose-6-phosphate and fructose-6-phosphate, a key step in glycolysis. By promoting glycolytic flux, GPI-1 supports glucose catabolism and energy production through the glycolytic pathway rather than directing glucose-6-phosphate into the pentose phosphate pathway (which generates NADPH and supports oxidative stress defense). In C. elegans, enhanced glycolysis is associated with reduced lifespan, while reduced glycolytic activity (e.g., via inhibition of downstream glycolytic enzymes) has been shown to extend lifespan through mechanisms involving AMPK activation and DAF-16/FOXO signaling. Thus, the normal pro-glycolytic function of gpi-1 is expected to promote glucose consumption and suppress longevity-associated metabolic reprogramming, placing it in the deregulated nutrient-sensing hallmark of aging.",
"confidence": 0.65,
"key_pathways": [
"glycolysis / glucose metabolism",
"DAF-2/insulin-IGF-1 nutrient sensing",
"pentose phosphate pathway diversion"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for gpi-1. The mechanistic reasoning is sound and well-grounded: GPI-1 promotes glycolytic flux, and in C. elegans, enhanced glycolysis is associated with reduced lifespan, while inhibiting glycolytic enzymes extends lifespan. The model correctly identifies the connection to AMPK and DAF-16/FOXO signaling. The pentose phosphate pathway diversion argument is also reasonable. Confidence of 0.65 is appropriately calibrated. Minor deduction: the reasoning is somewhat general/inferential rather than citing specific gpi-1 experimental data, but the logic is coherent and correct.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}