Gh
M. musculus
growth hormone
What the model saw
Gene: Gh Organism: Mus musculus Known functions: growth hormone. somatotropin. growth factor activity. growth hormone receptor binding. hormone activity.
View unredacted entry
growth hormone. somatotropin. growth factor activity. growth hormone receptor binding. hormone activity.
Solver output
Growth hormone (GH/somatotropin) signals through the GH receptor to activate the JAK2-STAT5 pathway, which in turn stimulates hepatic IGF-1 production. Elevated IGF-1 activates the PI3K-AKT-mTORC1 axis, a central nutrient/growth-sensing pathway whose chronic activation is strongly associated with accelerated aging and reduced lifespan. Conversely, loss-of-function mutations in GH or its receptor (e.g., Ames dwarf, Snell dwarf, and GHR-knockout mice) dramatically extend lifespan in mice, establishing GH signaling as a key anti-longevity axis. GH also promotes anabolic and pro-growth states that suppress autophagy and stress resistance pathways. The robust lifespan extension seen in GH-deficient or GH-resistant mouse models makes this one of the best-validated anti-longevity genes in mammals.
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 identifies Gh as anti_longevity with high confidence (0.93). The mechanistic reasoning is excellent and accurate: GH signals via JAK2-STAT5 to stimulate IGF-1, which activates PI3K-AKT-mTORC1, promoting aging. The model correctly cites Ames dwarf, Snell dwarf, and GHR-knockout mice as canonical examples of GH-deficient/resistant long-lived mice. The mechanism class of "deregulated_nutrient_sensing" is appropriate given the GH-IGF-1-mTOR axis involvement. This is one of the best-validated anti-longevity genes in mice and the model's reasoning reflects that well.
Raw API responses
solver
{
"reasoning": "Growth hormone (GH/somatotropin) signals through the GH receptor to activate the JAK2-STAT5 pathway, which in turn stimulates hepatic IGF-1 production. Elevated IGF-1 activates the PI3K-AKT-mTORC1 axis, a central nutrient/growth-sensing pathway whose chronic activation is strongly associated with accelerated aging and reduced lifespan. Conversely, loss-of-function mutations in GH or its receptor (e.g., Ames dwarf, Snell dwarf, and GHR-knockout mice) dramatically extend lifespan in mice, establishing GH signaling as a key anti-longevity axis. GH also promotes anabolic and pro-growth states that suppress autophagy and stress resistance pathways. The robust lifespan extension seen in GH-deficient or GH-resistant mouse models makes this one of the best-validated anti-longevity genes in mammals.",
"confidence": 0.93,
"key_pathways": [
"GH-IGF-1 axis / JAK2-STAT5 signaling",
"PI3K-AKT-mTORC1 nutrient sensing",
"Insulin/IGF-1 signaling pathway"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identifies Gh as anti_longevity with high confidence (0.93). The mechanistic reasoning is excellent and accurate: GH signals via JAK2-STAT5 to stimulate IGF-1, which activates PI3K-AKT-mTORC1, promoting aging. The model correctly cites Ames dwarf, Snell dwarf, and GHR-knockout mice as canonical examples of GH-deficient/resistant long-lived mice. The mechanism class of \"deregulated_nutrient_sensing\" is appropriate given the GH-IGF-1-mTOR axis involvement. This is one of the best-validated anti-longevity genes in mice and the model's reasoning reflects that well.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}