arr-1
C. elegans
Beta-arrestin arr-1
What the model saw
Gene: arr-1 Organism: Caenorhabditis elegans Known functions: Beta-arrestin arr-1. G protein-coupled receptor binding.
View unredacted entry
Beta-arrestin arr-1. G protein-coupled receptor binding.
Solver output
Beta-arrestins are scaffold proteins that bind activated GPCRs to mediate receptor desensitization and internalization, thereby attenuating downstream signaling. In C. elegans, arr-1 modulates GPCR signaling cascades relevant to chemosensory and neuroendocrine pathways. By dampening GPCR-coupled signaling (including potential insulin/IGF-1-like pathway inputs via neuroendocrine GPCRs), arr-1 could reduce pro-growth, nutrient-sensing signals that shorten lifespan. Reduced GPCR signaling through beta-arrestin-mediated desensitization is analogous to dampening IIS or other nutrient-sensing axes, which is generally associated with lifespan extension in C. elegans. Additionally, beta-arrestins can redirect signaling toward MAPK pathways in a G-protein-independent manner, adding complexity, but the dominant role in receptor downregulation supports a net pro-longevity classification.
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 pro_longevity but the ground truth is anti_longevity. The model's reasoning about beta-arrestin dampening GPCR signaling and thereby reducing pro-growth signals is speculative and ultimately incorrect. In C. elegans, arr-1 (beta-arrestin) loss-of-function studies suggest it plays an anti-longevity role, meaning arr-1 activity shortens lifespan rather than extending it. The model's logic that receptor desensitization would be analogous to dampening IIS is a plausible-sounding but incorrect mechanistic inference. The model had moderate confidence (0.55) but still got both the answer and the mechanism wrong.
Raw API responses
solver
{
"reasoning": "Beta-arrestins are scaffold proteins that bind activated GPCRs to mediate receptor desensitization and internalization, thereby attenuating downstream signaling. In C. elegans, arr-1 modulates GPCR signaling cascades relevant to chemosensory and neuroendocrine pathways. By dampening GPCR-coupled signaling (including potential insulin/IGF-1-like pathway inputs via neuroendocrine GPCRs), arr-1 could reduce pro-growth, nutrient-sensing signals that shorten lifespan. Reduced GPCR signaling through beta-arrestin-mediated desensitization is analogous to dampening IIS or other nutrient-sensing axes, which is generally associated with lifespan extension in C. elegans. Additionally, beta-arrestins can redirect signaling toward MAPK pathways in a G-protein-independent manner, adding complexity, but the dominant role in receptor downregulation supports a net pro-longevity classification.",
"confidence": 0.55,
"key_pathways": [
"GPCR desensitization and internalization",
"Insulin/IGF-1-like signaling (IIS) modulation via neuroendocrine GPCRs",
"Beta-arrestin scaffold signaling (G-protein-independent MAPK)"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about beta-arrestin dampening GPCR signaling and thereby reducing pro-growth signals is speculative and ultimately incorrect. In C. elegans, arr-1 (beta-arrestin) loss-of-function studies suggest it plays an anti-longevity role, meaning arr-1 activity shortens lifespan rather than extending it. The model's logic that receptor desensitization would be analogous to dampening IIS is a plausible-sounding but incorrect mechanistic inference. The model had moderate confidence (0.55) but still got both the answer and the mechanism wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}