Glyp
D. melanogaster
Glycogen phosphorylase
What the model saw
Gene: Glyp Organism: Drosophila melanogaster Known functions: Glycogen phosphorylase. glycogen phosphorylase. 1,4-alpha-oligoglucan phosphorylase activity. glycogen phosphorylase activity. protein homodimerization activity. pyridoxal phosphate binding.
View unredacted entry
Glycogen phosphorylase. glycogen phosphorylase. 1,4-alpha-oligoglucan phosphorylase activity. glycogen phosphorylase activity. protein homodimerization activity. pyridoxal phosphate binding.
Solver output
Glycogen phosphorylase (Glyp) catalyzes the rate-limiting step of glycogenolysis, cleaving glucose-1-phosphate from glycogen to mobilize stored glucose. Elevated glycogen phosphorylase activity increases circulating glucose and feeds into glycolytic and insulin/IGF-1 signaling pathways. In Drosophila, hyperactivation of nutrient-sensing pathways (IIS/TOR) is well-established to shorten lifespan, and excessive glucose mobilization would promote anabolic signaling and suppress FOXO-mediated pro-longevity transcription. Additionally, increased glycolytic flux can elevate reactive oxygen species production via mitochondrial respiration, contributing to oxidative stress. Loss-of-function or reduced activity of glycogen phosphorylase would be expected to conserve glycogen stores, dampen IIS/TOR signaling, and extend lifespan, consistent with the pro-longevity effects of dietary restriction and reduced glucose availability observed in flies.
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 Glyp (glycogen phosphorylase) in Drosophila. The mechanistic reasoning is biologically coherent: glycogen phosphorylase mobilizes glucose, which can feed into IIS/TOR signaling and promote anabolic pathways that shorten lifespan. The reasoning about reduced Glyp activity conserving glycogen and dampening nutrient-sensing pathways is plausible. The model appropriately connects glycogenolysis to known longevity-relevant pathways. Confidence of 0.72 is reasonable. The reasoning is somewhat speculative (connecting glycogen mobilization to IIS/TOR) but is mechanistically sound and consistent with known biology in Drosophila.
Raw API responses
solver
{
"reasoning": "Glycogen phosphorylase (Glyp) catalyzes the rate-limiting step of glycogenolysis, cleaving glucose-1-phosphate from glycogen to mobilize stored glucose. Elevated glycogen phosphorylase activity increases circulating glucose and feeds into glycolytic and insulin/IGF-1 signaling pathways. In Drosophila, hyperactivation of nutrient-sensing pathways (IIS/TOR) is well-established to shorten lifespan, and excessive glucose mobilization would promote anabolic signaling and suppress FOXO-mediated pro-longevity transcription. Additionally, increased glycolytic flux can elevate reactive oxygen species production via mitochondrial respiration, contributing to oxidative stress. Loss-of-function or reduced activity of glycogen phosphorylase would be expected to conserve glycogen stores, dampen IIS/TOR signaling, and extend lifespan, consistent with the pro-longevity effects of dietary restriction and reduced glucose availability observed in flies.",
"confidence": 0.72,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) / FOXO pathway",
"glycogenolysis / glucose mobilization",
"TOR nutrient-sensing pathway"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for Glyp (glycogen phosphorylase) in Drosophila. The mechanistic reasoning is biologically coherent: glycogen phosphorylase mobilizes glucose, which can feed into IIS/TOR signaling and promote anabolic pathways that shorten lifespan. The reasoning about reduced Glyp activity conserving glycogen and dampening nutrient-sensing pathways is plausible. The model appropriately connects glycogenolysis to known longevity-relevant pathways. Confidence of 0.72 is reasonable. The reasoning is somewhat speculative (connecting glycogen mobilization to IIS/TOR) but is mechanistically sound and consistent with known biology in Drosophila.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}