Fgf21
M. musculus
fibroblast growth factor 21
What the model saw
Gene: Fgf21 Organism: Mus musculus Known functions: fibroblast growth factor 21. fibroblast growth factor receptor binding. growth factor activity.
View unredacted entry
fibroblast growth factor 21. fibroblast growth factor receptor binding. growth factor activity.
Solver output
FGF21 is a hepatokine and endocrine member of the fibroblast growth factor family that acts as a key metabolic regulator by binding to FGFR1c/β-Klotho co-receptor complexes. It functions as a potent activator of the PPARα-FGF21 axis during fasting/starvation, improving insulin sensitivity, glucose uptake, and lipid metabolism — all processes tightly linked to nutrient-sensing pathways (insulin/IGF-1 and mTOR signaling). Transgenic mice overexpressing Fgf21 show significantly extended lifespan (~36% increase), reduced adiposity, improved metabolic homeostasis, and delayed age-related pathologies. FGF21 also suppresses growth hormone/IGF-1 signaling, mimicking the longevity-promoting effects seen in caloric restriction and GH-deficient dwarf mice. Its role in coordinating the fasting response and dampening anabolic nutrient-sensing cascades places it firmly within 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 pro_longevity for Fgf21 in Mus musculus with high confidence (0.82). The mechanistic reasoning is excellent and accurate: FGF21 overexpression in transgenic mice does extend lifespan (~36%), it does act through PPARα, suppresses GH/IGF-1 signaling, and improves metabolic homeostasis. The classification under "deregulated_nutrient_sensing" is appropriate given FGF21's role in the fasting response and insulin/IGF-1/mTOR pathway modulation. All key pathways cited are well-supported by the literature.
Raw API responses
solver
{
"reasoning": "FGF21 is a hepatokine and endocrine member of the fibroblast growth factor family that acts as a key metabolic regulator by binding to FGFR1c/β-Klotho co-receptor complexes. It functions as a potent activator of the PPARα-FGF21 axis during fasting/starvation, improving insulin sensitivity, glucose uptake, and lipid metabolism — all processes tightly linked to nutrient-sensing pathways (insulin/IGF-1 and mTOR signaling). Transgenic mice overexpressing Fgf21 show significantly extended lifespan (~36% increase), reduced adiposity, improved metabolic homeostasis, and delayed age-related pathologies. FGF21 also suppresses growth hormone/IGF-1 signaling, mimicking the longevity-promoting effects seen in caloric restriction and GH-deficient dwarf mice. Its role in coordinating the fasting response and dampening anabolic nutrient-sensing cascades places it firmly within the deregulated nutrient-sensing hallmark of aging.",
"confidence": 0.82,
"key_pathways": [
"PPARα-FGF21 fasting axis",
"Insulin/IGF-1 and mTOR nutrient-sensing signaling",
"Growth hormone/IGF-1 axis suppression"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Fgf21 in Mus musculus with high confidence (0.82). The mechanistic reasoning is excellent and accurate: FGF21 overexpression in transgenic mice does extend lifespan (~36%), it does act through PPARα, suppresses GH/IGF-1 signaling, and improves metabolic homeostasis. The classification under \"deregulated_nutrient_sensing\" is appropriate given FGF21's role in the fasting response and insulin/IGF-1/mTOR pathway modulation. All key pathways cited are well-supported by the literature.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}