Pparg
M. musculus
peroxisome proliferator activated receptor gamma
What the model saw
Gene: Pparg Organism: Mus musculus Known functions: peroxisome proliferator activated receptor gamma. peroxisome proliferator-activated receptor gamma. DNA binding. DNA binding domain binding. DNA-binding transcription activator activity, RNA polymerase II-specific. DNA-binding transcription factor activity. DNA-binding transcription factor binding. DNA-binding transcription repressor activity, RNA polymerase II-specific. E-box binding. LBD domain binding. R-SMAD binding. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II core promoter sequence-specific DNA binding. RNA polymerase II transcription regulatory region sequence-specific DNA binding. STAT family protein binding. WW domain binding. alpha-actinin binding. arachidonate binding. chromatin binding. double-stranded DNA binding. enzyme binding. identical protein binding. nuclear estrogen receptor binding. nuclear receptor activity. nuclear retinoid X receptor binding. nucleic acid binding. peptide binding. promoter-specific chromatin binding. protein binding. protein phosphatase binding. sequence-specific DNA binding. transcription cis-regulatory region binding. transcription coactivator binding. transcription coregulator binding. zinc ion binding.
View unredacted entry
peroxisome proliferator activated receptor gamma. peroxisome proliferator-activated receptor gamma. DNA binding. DNA binding domain binding. DNA-binding transcription activator activity, RNA polymerase II-specific. DNA-binding transcription factor activity. DNA-binding transcription factor binding. DNA-binding transcription repressor activity, RNA polymerase II-specific. E-box binding. LBD domain binding. R-SMAD binding. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II core promoter sequence-specific DNA binding. RNA polymerase II transcription regulatory region sequence-specific DNA binding. STAT family protein binding. WW domain binding. alpha-actinin binding. arachidonate binding. chromatin binding. double-stranded DNA binding. enzyme binding. identical protein binding. nuclear estrogen receptor binding. nuclear receptor activity. nuclear retinoid X receptor binding. nucleic acid binding. peptide binding. promoter-specific chromatin binding. protein binding. protein phosphatase binding. sequence-specific DNA binding. transcription cis-regulatory region binding. transcription coactivator binding. transcription coregulator binding. zinc ion binding.
Solver output
PPARγ is a ligand-activated nuclear receptor and master transcriptional regulator of adipogenesis, lipid metabolism, and insulin sensitization. It heterodimerizes with RXR (evidenced by nuclear retinoid X receptor binding) and binds PPAR response elements to activate genes involved in fatty acid uptake, storage, and glucose homeostasis, directly coupling nutrient/lipid sensing to transcriptional output. Activation of PPARγ improves insulin sensitivity and reduces lipotoxicity, counteracting metabolic dysfunction that accelerates aging. Its ability to bind R-SMADs and STAT family proteins also links it to anti-inflammatory and anti-fibrotic signaling, which suppresses chronic inflammation—a key aging hallmark. In mice, PPARγ agonism (e.g., thiazolidinediones) extends healthspan and reduces age-related metabolic disease, though adipose-specific overactivation can have complex effects. The net balance of evidence in Mus musculus supports a pro-longevity role through improved nutrient sensing and metabolic homeostasis.
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 Pparg in Mus musculus. The mechanistic reasoning is solid and well-grounded: PPARγ as a master regulator of adipogenesis, lipid metabolism, and insulin sensitization, with connections to nutrient sensing, anti-inflammatory signaling via STAT and R-SMAD interactions, and RXR heterodimerization. The model appropriately notes the complexity (adipose-specific overactivation can have complex effects) while arriving at the correct net conclusion. The mechanism class of "deregulated_nutrient_sensing" is reasonable. Confidence of 0.62 is appropriately moderate given the complexity of PPARγ biology. Minor deduction: the claim that "PPARγ agonism extends healthspan in mice" is somewhat overstated/not fully established in the literature, but the overall reasoning is sound.
Raw API responses
solver
{
"reasoning": "PPARγ is a ligand-activated nuclear receptor and master transcriptional regulator of adipogenesis, lipid metabolism, and insulin sensitization. It heterodimerizes with RXR (evidenced by nuclear retinoid X receptor binding) and binds PPAR response elements to activate genes involved in fatty acid uptake, storage, and glucose homeostasis, directly coupling nutrient/lipid sensing to transcriptional output. Activation of PPARγ improves insulin sensitivity and reduces lipotoxicity, counteracting metabolic dysfunction that accelerates aging. Its ability to bind R-SMADs and STAT family proteins also links it to anti-inflammatory and anti-fibrotic signaling, which suppresses chronic inflammation—a key aging hallmark. In mice, PPARγ agonism (e.g., thiazolidinediones) extends healthspan and reduces age-related metabolic disease, though adipose-specific overactivation can have complex effects. The net balance of evidence in Mus musculus supports a pro-longevity role through improved nutrient sensing and metabolic homeostasis.",
"confidence": 0.62,
"key_pathways": [
"PPARγ-RXR nuclear receptor / lipid and glucose homeostasis",
"Insulin sensitization and adipogenesis transcriptional program",
"Anti-inflammatory / R-SMAD and STAT signaling crosstalk"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Pparg in Mus musculus. The mechanistic reasoning is solid and well-grounded: PPARγ as a master regulator of adipogenesis, lipid metabolism, and insulin sensitization, with connections to nutrient sensing, anti-inflammatory signaling via STAT and R-SMAD interactions, and RXR heterodimerization. The model appropriately notes the complexity (adipose-specific overactivation can have complex effects) while arriving at the correct net conclusion. The mechanism class of \"deregulated_nutrient_sensing\" is reasonable. Confidence of 0.62 is appropriately moderate given the complexity of PPARγ biology. Minor deduction: the claim that \"PPARγ agonism extends healthspan in mice\" is somewhat overstated/not fully established in the literature, but the overall reasoning is sound.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}