Plau
M. musculus
plasminogen activator, urokinase
What the model saw
Gene: Plau Organism: Mus musculus Known functions: plasminogen activator, urokinase. urokinase-type plasminogen activator. peptidase activity. protein binding. receptor ligand activity. serine-type endopeptidase activity.
View unredacted entry
plasminogen activator, urokinase. urokinase-type plasminogen activator. peptidase activity. protein binding. receptor ligand activity. serine-type endopeptidase activity.
Solver output
Plau encodes urokinase-type plasminogen activator (uPA), a serine-type endopeptidase that cleaves plasminogen into plasmin, broadly activating extracellular proteolysis. Elevated uPA/plasmin activity drives matrix metalloproteinase activation, ECM degradation, and release of pro-inflammatory cytokines and growth factors, contributing to a chronic inflammatory tissue microenvironment associated with aging pathologies. uPA also acts as a receptor ligand (via uPAR/PLAUR), activating downstream signaling cascades (ERK, NF-κB) that promote cellular senescence and tissue remodeling dysfunction. Overactivation of the uPA–plasmin axis is linked to age-associated fibrosis, atherosclerosis, and tumor progression in mice, all of which shorten healthspan and lifespan. Thus, the normal pro-proteolytic function of Plau is expected to be net detrimental 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 predicted anti_longevity for Plau (urokinase-type plasminogen activator), but the ground truth is pro_longevity. The model's reasoning focused on the pro-inflammatory and ECM-degrading aspects of uPA activity, arguing these would be net detrimental to longevity. However, the actual GenAge classification is pro_longevity, suggesting that Plau's role in plasminogen activation and fibrinolysis is beneficial for longevity (e.g., through clearance of fibrin clots, maintaining tissue homeostasis, or other protective mechanisms). The model's mechanistic reasoning about chronic inflammation and ECM degradation being harmful is plausible in some contexts but misses the pro-longevity role of this gene in mice. The model had moderate confidence (0.62) but was still clearly wrong on both the answer and the mechanism.
Raw API responses
solver
{
"reasoning": "Plau encodes urokinase-type plasminogen activator (uPA), a serine-type endopeptidase that cleaves plasminogen into plasmin, broadly activating extracellular proteolysis. Elevated uPA/plasmin activity drives matrix metalloproteinase activation, ECM degradation, and release of pro-inflammatory cytokines and growth factors, contributing to a chronic inflammatory tissue microenvironment associated with aging pathologies. uPA also acts as a receptor ligand (via uPAR/PLAUR), activating downstream signaling cascades (ERK, NF-κB) that promote cellular senescence and tissue remodeling dysfunction. Overactivation of the uPA–plasmin axis is linked to age-associated fibrosis, atherosclerosis, and tumor progression in mice, all of which shorten healthspan and lifespan. Thus, the normal pro-proteolytic function of Plau is expected to be net detrimental to longevity.",
"confidence": 0.62,
"key_pathways": [
"uPA-plasmin extracellular proteolysis cascade",
"uPAR-mediated NF-κB/ERK pro-inflammatory signaling",
"matrix metalloproteinase activation and ECM remodeling"
],
"mechanism_class": "chronic_inflammation",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity for Plau (urokinase-type plasminogen activator), but the ground truth is pro_longevity. The model's reasoning focused on the pro-inflammatory and ECM-degrading aspects of uPA activity, arguing these would be net detrimental to longevity. However, the actual GenAge classification is pro_longevity, suggesting that Plau's role in plasminogen activation and fibrinolysis is beneficial for longevity (e.g., through clearance of fibrin clots, maintaining tissue homeostasis, or other protective mechanisms). The model's mechanistic reasoning about chronic inflammation and ECM degradation being harmful is plausible in some contexts but misses the pro-longevity role of this gene in mice. The model had moderate confidence (0.62) but was still clearly wrong on both the answer and the mechanism.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}