Foxm1
M. musculus
forkhead box M1
What the model saw
Gene: Foxm1 Organism: Mus musculus Known functions: forkhead box M1. forkhead box protein M1. DNA binding. DNA-binding transcription factor activity. RNA polymerase II transcription regulatory region sequence-specific DNA binding. phosphatidylinositol 3-kinase catalytic subunit binding. phosphatidylinositol 3-kinase regulatory subunit binding. protein binding. protein kinase binding. protein serine/threonine kinase binding. sequence-specific DNA binding. transcription cis-regulatory region binding.
View unredacted entry
forkhead box M1. forkhead box protein M1. DNA binding. DNA-binding transcription factor activity. RNA polymerase II transcription regulatory region sequence-specific DNA binding. phosphatidylinositol 3-kinase catalytic subunit binding. phosphatidylinositol 3-kinase regulatory subunit binding. protein binding. protein kinase binding. protein serine/threonine kinase binding. sequence-specific DNA binding. transcription cis-regulatory region binding.
Solver output
FOXM1 is a forkhead box transcription factor that drives expression of cell cycle progression genes (Cyclin B, CDK1, PLK1, Aurora kinases) and is a master regulator of mitotic entry and proliferation. Its activity is strongly suppressed during cellular senescence, and its re-expression can bypass senescence, while its loss accelerates senescence and tissue aging. Although FOXM1 promotes tissue regeneration and stem cell maintenance, its primary role as a pro-proliferative, anti-senescence factor means that sustained high activity is associated with cancer and age-related pathologies rather than longevity extension. FOXM1 also interacts with PI3K regulatory and catalytic subunits, linking it to the PI3K/AKT nutrient-sensing axis, which when overactivated is broadly anti-longevity. Furthermore, FOXM1 expression declines with age in multiple tissues, and its overactivation promotes genomic instability through dysregulated mitosis. Thus, while FOXM1 opposes senescence acutely, its net effect on organismal longevity is anti-longevity due to promotion of proliferative stress, genomic instability, and oncogenic signaling.
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 Foxm1, but the ground truth is pro_longevity. The model's reasoning is internally contradictory - it acknowledges that FOXM1 promotes tissue regeneration, stem cell maintenance, and opposes senescence, but then concludes it is anti-longevity due to cancer risk and genomic instability. The actual pro-longevity classification likely reflects FOXM1's role in maintaining tissue homeostasis, stem cell function, and opposing cellular senescence - which the model partially identified but then dismissed. The model's reasoning about PI3K/AKT overactivation being anti-longevity is speculative and not well-supported in the context of FOXM1's actual effects. The model was fairly confident (0.72) in its wrong answer. The mechanistic reasoning is also incorrect in its final conclusion, though it touches on some relevant biology.
Raw API responses
solver
{
"reasoning": "FOXM1 is a forkhead box transcription factor that drives expression of cell cycle progression genes (Cyclin B, CDK1, PLK1, Aurora kinases) and is a master regulator of mitotic entry and proliferation. Its activity is strongly suppressed during cellular senescence, and its re-expression can bypass senescence, while its loss accelerates senescence and tissue aging. Although FOXM1 promotes tissue regeneration and stem cell maintenance, its primary role as a pro-proliferative, anti-senescence factor means that sustained high activity is associated with cancer and age-related pathologies rather than longevity extension. FOXM1 also interacts with PI3K regulatory and catalytic subunits, linking it to the PI3K/AKT nutrient-sensing axis, which when overactivated is broadly anti-longevity. Furthermore, FOXM1 expression declines with age in multiple tissues, and its overactivation promotes genomic instability through dysregulated mitosis. Thus, while FOXM1 opposes senescence acutely, its net effect on organismal longevity is anti-longevity due to promotion of proliferative stress, genomic instability, and oncogenic signaling.",
"confidence": 0.72,
"key_pathways": [
"Cell cycle transcriptional regulation (Cyclin B/CDK1/PLK1 axis)",
"PI3K/AKT signaling",
"Cellular senescence bypass"
],
"mechanism_class": "cellular_senescence",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity for Foxm1, but the ground truth is pro_longevity. The model's reasoning is internally contradictory - it acknowledges that FOXM1 promotes tissue regeneration, stem cell maintenance, and opposes senescence, but then concludes it is anti-longevity due to cancer risk and genomic instability. The actual pro-longevity classification likely reflects FOXM1's role in maintaining tissue homeostasis, stem cell function, and opposing cellular senescence - which the model partially identified but then dismissed. The model's reasoning about PI3K/AKT overactivation being anti-longevity is speculative and not well-supported in the context of FOXM1's actual effects. The model was fairly confident (0.72) in its wrong answer. The mechanistic reasoning is also incorrect in its final conclusion, though it touches on some relevant biology.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}