Fn1
M. musculus
fibronectin 1
What the model saw
Gene: Fn1 Organism: Mus musculus Known functions: fibronectin 1. fibronectin. extracellular matrix structural constituent. identical protein binding. integrin binding. mercury ion binding. peptidase activator activity. protease binding. protein binding. proteoglycan binding. receptor ligand activity. signaling receptor binding.
View unredacted entry
fibronectin 1. fibronectin. extracellular matrix structural constituent. identical protein binding. integrin binding. mercury ion binding. peptidase activator activity. protease binding. protein binding. proteoglycan binding. receptor ligand activity. signaling receptor binding.
Solver output
Fibronectin 1 (Fn1) is a major extracellular matrix (ECM) glycoprotein that acts as a structural constituent of the ECM and a ligand for integrin receptors, activating downstream pro-survival and pro-fibrotic signaling cascades (e.g., FAK/PI3K/Akt, MAPK). With aging, fibronectin accumulates in tissues and is a key component of the senescence-associated secretory phenotype (SASP), where it promotes chronic low-grade inflammation and paracrine senescence in neighboring cells. Its integrin-binding and receptor ligand activities drive integrin-mediated mechanosignaling that reinforces ECM stiffening, a hallmark of aged tissues that promotes cellular senescence and impairs stem cell function. Additionally, Fn1's protease binding and peptidase activator activity can modulate matrix metalloproteinase activity, contributing to aberrant ECM remodeling characteristic of aged tissues. The net effect of elevated Fn1 function is therefore pro-fibrotic, pro-inflammatory, and pro-senescent, opposing 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 but the ground truth is pro_longevity. The model's reasoning focused on fibronectin's role in SASP, ECM stiffening, and pro-fibrotic/pro-senescent signaling as reasons it would be anti-longevity. However, the ground truth indicates Fn1 is pro_longevity in mice. The mechanistic reasoning is also incorrect - while fibronectin does accumulate with aging and can be part of SASP, the model failed to account for fibronectin's essential roles in tissue repair, cell survival, and structural integrity that support longevity. The model was moderately confident (0.62) in the wrong direction. The reasoning quality is poor because it selectively emphasized negative aspects of fibronectin while ignoring its essential pro-survival functions.
Raw API responses
solver
{
"reasoning": "Fibronectin 1 (Fn1) is a major extracellular matrix (ECM) glycoprotein that acts as a structural constituent of the ECM and a ligand for integrin receptors, activating downstream pro-survival and pro-fibrotic signaling cascades (e.g., FAK/PI3K/Akt, MAPK). With aging, fibronectin accumulates in tissues and is a key component of the senescence-associated secretory phenotype (SASP), where it promotes chronic low-grade inflammation and paracrine senescence in neighboring cells. Its integrin-binding and receptor ligand activities drive integrin-mediated mechanosignaling that reinforces ECM stiffening, a hallmark of aged tissues that promotes cellular senescence and impairs stem cell function. Additionally, Fn1's protease binding and peptidase activator activity can modulate matrix metalloproteinase activity, contributing to aberrant ECM remodeling characteristic of aged tissues. The net effect of elevated Fn1 function is therefore pro-fibrotic, pro-inflammatory, and pro-senescent, opposing longevity.",
"confidence": 0.62,
"key_pathways": [
"integrin-FAK signaling / ECM stiffening",
"senescence-associated secretory phenotype (SASP)",
"ECM remodeling via protease/MMP activation"
],
"mechanism_class": "cellular_senescence",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity but the ground truth is pro_longevity. The model's reasoning focused on fibronectin's role in SASP, ECM stiffening, and pro-fibrotic/pro-senescent signaling as reasons it would be anti-longevity. However, the ground truth indicates Fn1 is pro_longevity in mice. The mechanistic reasoning is also incorrect - while fibronectin does accumulate with aging and can be part of SASP, the model failed to account for fibronectin's essential roles in tissue repair, cell survival, and structural integrity that support longevity. The model was moderately confident (0.62) in the wrong direction. The reasoning quality is poor because it selectively emphasized negative aspects of fibronectin while ignoring its essential pro-survival functions.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": true
}