Gdf15
M. musculus
growth differentiation factor 15
What the model saw
Gene: Gdf15 Organism: Mus musculus Known functions: growth differentiation factor 15. growth/differentiation factor 15. cytokine activity. growth factor activity. hormone activity. protein homodimerization activity.
View unredacted entry
growth differentiation factor 15. growth/differentiation factor 15. cytokine activity. growth factor activity. hormone activity. protein homodimerization activity.
Solver output
GDF15 is a stress-responsive cytokine and divergent TGF-β superfamily member that signals through the GFRAL receptor in the brainstem to suppress appetite and reduce body weight, effects associated with metabolic improvements and extended healthspan. Elevated GDF15 is induced by mitochondrial stress, DNA damage, and metabolic dysfunction, acting as a mitokine that coordinates systemic responses to cellular stress. In mice, GDF15 overexpression reduces adiposity and improves insulin sensitivity, while GDF15 knockout leads to increased body weight and age-related metabolic decline. Its hormone/cytokine activity mediates intercellular communication between stressed tissues and distant organs, a hallmark of aging-related signaling. The homodimerization activity is required for its secreted, active form that drives these systemic metabolic benefits linked to 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 pro_longevity for Gdf15 in Mus musculus with a reasonable confidence of 0.62. The mechanistic reasoning is detailed and accurate: GDF15 signals through GFRAL in the brainstem to suppress appetite and reduce body weight, acts as a mitokine under stress conditions, and its overexpression improves metabolic parameters while knockout leads to metabolic decline. The mechanism class of "altered_intercellular_communication" is appropriate given GDF15's role as a secreted cytokine/hormone mediating inter-organ communication. The key pathways identified (GFRAL-RET signaling, TGF-β superfamily, mitokine signaling) are all well-supported by the literature.
Raw API responses
solver
{
"reasoning": "GDF15 is a stress-responsive cytokine and divergent TGF-β superfamily member that signals through the GFRAL receptor in the brainstem to suppress appetite and reduce body weight, effects associated with metabolic improvements and extended healthspan. Elevated GDF15 is induced by mitochondrial stress, DNA damage, and metabolic dysfunction, acting as a mitokine that coordinates systemic responses to cellular stress. In mice, GDF15 overexpression reduces adiposity and improves insulin sensitivity, while GDF15 knockout leads to increased body weight and age-related metabolic decline. Its hormone/cytokine activity mediates intercellular communication between stressed tissues and distant organs, a hallmark of aging-related signaling. The homodimerization activity is required for its secreted, active form that drives these systemic metabolic benefits linked to longevity.",
"confidence": 0.62,
"key_pathways": [
"GFRAL-RET signaling (appetite/energy balance)",
"TGF-β superfamily stress signaling",
"mitokine-mediated inter-organ communication"
],
"mechanism_class": "altered_intercellular_communication",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Gdf15 in Mus musculus with a reasonable confidence of 0.62. The mechanistic reasoning is detailed and accurate: GDF15 signals through GFRAL in the brainstem to suppress appetite and reduce body weight, acts as a mitokine under stress conditions, and its overexpression improves metabolic parameters while knockout leads to metabolic decline. The mechanism class of \"altered_intercellular_communication\" is appropriate given GDF15's role as a secreted cytokine/hormone mediating inter-organ communication. The key pathways identified (GFRAL-RET signaling, TGF-β superfamily, mitokine signaling) are all well-supported by the literature.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}