Igf1
M. musculus
insulin-like growth factor 1
What the model saw
Gene: Igf1 Organism: Mus musculus Known functions: insulin-like growth factor 1. insulin-like growth factor 1; insulin-like growth factor I. growth factor activity. hormone activity. insulin receptor binding. insulin-like growth factor receptor binding. integrin binding. protein binding. protein serine/threonine kinase activator activity. receptor ligand activity. steroid binding. transmembrane receptor protein tyrosine kinase activator activity.
View unredacted entry
insulin-like growth factor 1. insulin-like growth factor 1; insulin-like growth factor I. growth factor activity. hormone activity. insulin receptor binding. insulin-like growth factor receptor binding. integrin binding. protein binding. protein serine/threonine kinase activator activity. receptor ligand activity. steroid binding. transmembrane receptor protein tyrosine kinase activator activity.
Solver output
IGF-1 is the primary ligand for the IGF-1 receptor (IGF1R), and its binding activates the PI3K/AKT/mTOR and RAS/MAPK signaling cascades — the core nutrient-sensing and growth-promoting pathways. Reduced IGF-1/insulin signaling is one of the most conserved pro-longevity interventions across model organisms; Igf1 hypomorphic and liver-specific knockout mice show significantly extended lifespan. As a transmembrane receptor protein tyrosine kinase activator and protein serine/threonine kinase activator, IGF-1 drives anabolic signaling that suppresses FOXO transcription factors and autophagy, thereby opposing stress resistance and longevity. Its normal function thus promotes growth and reproduction at the expense of somatic maintenance, a classic antagonistic pleiotropy scenario. The strong genetic and pharmacological evidence in mice firmly places IGF-1 as an anti-longevity factor within the IIS (insulin/IGF-1 signaling) axis.
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" with very high confidence (0.95), but the ground truth is "unclear." While the mechanistic reasoning about IGF-1's role in the IIS axis is largely correct and well-articulated, the GenAge database classifies Igf1's longevity influence as unclear in mice. This likely reflects the complexity of IGF-1's effects — for example, some studies show that IGF-1 deficiency extends lifespan while others show context-dependent or tissue-specific effects that complicate a simple anti-longevity classification. The model was overconfident and failed to account for the nuance and conflicting evidence that led GenAge curators to assign an "unclear" designation. The mechanistic description is reasonable but the conclusion drawn from it is too definitive.
Raw API responses
solver
{
"reasoning": "IGF-1 is the primary ligand for the IGF-1 receptor (IGF1R), and its binding activates the PI3K/AKT/mTOR and RAS/MAPK signaling cascades — the core nutrient-sensing and growth-promoting pathways. Reduced IGF-1/insulin signaling is one of the most conserved pro-longevity interventions across model organisms; Igf1 hypomorphic and liver-specific knockout mice show significantly extended lifespan. As a transmembrane receptor protein tyrosine kinase activator and protein serine/threonine kinase activator, IGF-1 drives anabolic signaling that suppresses FOXO transcription factors and autophagy, thereby opposing stress resistance and longevity. Its normal function thus promotes growth and reproduction at the expense of somatic maintenance, a classic antagonistic pleiotropy scenario. The strong genetic and pharmacological evidence in mice firmly places IGF-1 as an anti-longevity factor within the IIS (insulin/IGF-1 signaling) axis.",
"confidence": 0.95,
"key_pathways": [
"IGF-1/IGF1R → PI3K/AKT/mTORC1 signaling",
"FOXO transcription factor suppression",
"IIS (insulin/IGF-1 signaling) axis"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted \"anti_longevity\" with very high confidence (0.95), but the ground truth is \"unclear.\" While the mechanistic reasoning about IGF-1's role in the IIS axis is largely correct and well-articulated, the GenAge database classifies Igf1's longevity influence as unclear in mice. This likely reflects the complexity of IGF-1's effects — for example, some studies show that IGF-1 deficiency extends lifespan while others show context-dependent or tissue-specific effects that complicate a simple anti-longevity classification. The model was overconfident and failed to account for the nuance and conflicting evidence that led GenAge curators to assign an \"unclear\" designation. The mechanistic description is reasonable but the conclusion drawn from it is too definitive.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": true
}