Ghrh
M. musculus
growth hormone releasing hormone
What the model saw
Gene: Ghrh Organism: Mus musculus Known functions: growth hormone releasing hormone. somatoliberin. growth hormone-releasing hormone activity. growth hormone-releasing hormone receptor binding. hormone activity. neuropeptide hormone activity. peptide hormone receptor binding. protein binding. signaling receptor binding.
View unredacted entry
growth hormone releasing hormone. somatoliberin. growth hormone-releasing hormone activity. growth hormone-releasing hormone receptor binding. hormone activity. neuropeptide hormone activity. peptide hormone receptor binding. protein binding. signaling receptor binding.
Solver output
GHRH (Growth Hormone-Releasing Hormone / Somatoliberin) is the hypothalamic peptide that stimulates pituitary release of growth hormone (GH). GH in turn drives hepatic IGF-1 production, activating the GH/IGF-1 axis — a central nutrient-sensing and anabolic signaling pathway. In mice, loss-of-function mutations in this axis (e.g., Ames dwarf, Snell dwarf, GH receptor knockout) consistently extend lifespan, while elevated GH/IGF-1 signaling shortens it. GHRH acts as the upstream activator of this pro-aging axis by binding its receptor (GHRHR) on somatotrophs, making its normal function pro-growth and anti-longevity. Reduced GHRH signaling dampens GH/IGF-1 output, lowering downstream PI3K/AKT/mTOR activity, which is associated with improved stress resistance and extended lifespan in multiple model organisms. Thus, the normal (gain-of-function) activity of Ghrh promotes the GH/IGF-1 signaling cascade that opposes longevity.
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 Ghrh in Mus musculus with high confidence (0.82). The mechanistic reasoning is excellent and accurate: GHRH stimulates GH release, which drives IGF-1 production, activating the GH/IGF-1 axis. Loss-of-function mutations in this axis (Ames dwarf, Snell dwarf, GHR knockout) extend lifespan, while elevated signaling shortens it. The model correctly identifies GHRH as the upstream activator of this pro-aging axis. The mechanism class of "deregulated_nutrient_sensing" is appropriate given the GH/IGF-1/mTOR connections. The reasoning is thorough, biologically accurate, and well-supported by the literature.
Raw API responses
solver
{
"reasoning": "GHRH (Growth Hormone-Releasing Hormone / Somatoliberin) is the hypothalamic peptide that stimulates pituitary release of growth hormone (GH). GH in turn drives hepatic IGF-1 production, activating the GH/IGF-1 axis — a central nutrient-sensing and anabolic signaling pathway. In mice, loss-of-function mutations in this axis (e.g., Ames dwarf, Snell dwarf, GH receptor knockout) consistently extend lifespan, while elevated GH/IGF-1 signaling shortens it. GHRH acts as the upstream activator of this pro-aging axis by binding its receptor (GHRHR) on somatotrophs, making its normal function pro-growth and anti-longevity. Reduced GHRH signaling dampens GH/IGF-1 output, lowering downstream PI3K/AKT/mTOR activity, which is associated with improved stress resistance and extended lifespan in multiple model organisms. Thus, the normal (gain-of-function) activity of Ghrh promotes the GH/IGF-1 signaling cascade that opposes longevity.",
"confidence": 0.82,
"key_pathways": [
"GH/IGF-1 signaling axis",
"hypothalamic-pituitary somatotroph axis",
"PI3K/AKT/mTOR nutrient sensing"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for Ghrh in Mus musculus with high confidence (0.82). The mechanistic reasoning is excellent and accurate: GHRH stimulates GH release, which drives IGF-1 production, activating the GH/IGF-1 axis. Loss-of-function mutations in this axis (Ames dwarf, Snell dwarf, GHR knockout) extend lifespan, while elevated signaling shortens it. The model correctly identifies GHRH as the upstream activator of this pro-aging axis. The mechanism class of \"deregulated_nutrient_sensing\" is appropriate given the GH/IGF-1/mTOR connections. The reasoning is thorough, biologically accurate, and well-supported by the literature.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}