Adra1a
M. musculus
adrenergic receptor, alpha 1a
What the model saw
Gene: Adra1a Organism: Mus musculus Known functions: adrenergic receptor, alpha 1a. alpha-1A adrenergic receptor. G protein-coupled receptor activity. adrenergic receptor activity. alpha1-adrenergic receptor activity. protein heterodimerization activity.
View unredacted entry
adrenergic receptor, alpha 1a. alpha-1A adrenergic receptor. G protein-coupled receptor activity. adrenergic receptor activity. alpha1-adrenergic receptor activity. protein heterodimerization activity.
Solver output
Adra1a encodes the alpha-1A adrenergic receptor, a GPCR that mediates sympathetic nervous system signaling via catecholamines (norepinephrine/epinephrine). Chronic activation of alpha-1 adrenergic signaling promotes vasoconstriction, cardiac hypertrophy, and sustained sympathoadrenal tone — all hallmarks of age-associated cardiovascular deterioration. Elevated sympathetic nervous system activity is a well-established driver of aging-related pathology, including hypertension, cardiac fibrosis, and metabolic dysregulation. The receptor's heterodimerization activity can amplify downstream Gq/11-coupled signaling (IP3/DAG/PKC pathway), contributing to pro-hypertrophic and pro-inflammatory cascades. Sustained alpha-1A adrenergic signaling thus represents a form of deregulated intercellular communication that accelerates age-related organ dysfunction rather than promoting 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 follows a plausible but ultimately incorrect narrative — it assumed that alpha-1A adrenergic receptor activation is harmful due to sympathoadrenal overactivation, cardiac hypertrophy, and vasoconstriction. However, research has shown that Adra1a (alpha-1A adrenergic receptor) actually has cardioprotective effects and promotes longevity in mice. Studies by Perez et al. demonstrated that alpha-1A adrenergic receptor signaling is protective against cardiac failure and that transgenic overexpression of Adra1a extends lifespan in mice. The model conflated general sympathetic nervous system overactivation with the specific role of the alpha-1A receptor subtype, which has distinct (and often protective) downstream signaling compared to other adrenergic receptor subtypes. The confidence of 0.62 is moderate but the reasoning led to the wrong conclusion with a mechanistically incorrect explanation.
Raw API responses
solver
{
"reasoning": "Adra1a encodes the alpha-1A adrenergic receptor, a GPCR that mediates sympathetic nervous system signaling via catecholamines (norepinephrine/epinephrine). Chronic activation of alpha-1 adrenergic signaling promotes vasoconstriction, cardiac hypertrophy, and sustained sympathoadrenal tone — all hallmarks of age-associated cardiovascular deterioration. Elevated sympathetic nervous system activity is a well-established driver of aging-related pathology, including hypertension, cardiac fibrosis, and metabolic dysregulation. The receptor's heterodimerization activity can amplify downstream Gq/11-coupled signaling (IP3/DAG/PKC pathway), contributing to pro-hypertrophic and pro-inflammatory cascades. Sustained alpha-1A adrenergic signaling thus represents a form of deregulated intercellular communication that accelerates age-related organ dysfunction rather than promoting longevity.",
"confidence": 0.62,
"key_pathways": [
"sympathoadrenal/catecholamine signaling",
"Gq/11-PKC-IP3 cascade",
"cardiac hypertrophy and vasoconstriction"
],
"mechanism_class": "altered_intercellular_communication",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity but the ground truth is pro_longevity. The model's reasoning follows a plausible but ultimately incorrect narrative — it assumed that alpha-1A adrenergic receptor activation is harmful due to sympathoadrenal overactivation, cardiac hypertrophy, and vasoconstriction. However, research has shown that Adra1a (alpha-1A adrenergic receptor) actually has cardioprotective effects and promotes longevity in mice. Studies by Perez et al. demonstrated that alpha-1A adrenergic receptor signaling is protective against cardiac failure and that transgenic overexpression of Adra1a extends lifespan in mice. The model conflated general sympathetic nervous system overactivation with the specific role of the alpha-1A receptor subtype, which has distinct (and often protective) downstream signaling compared to other adrenergic receptor subtypes. The confidence of 0.62 is moderate but the reasoning led to the wrong conclusion with a mechanistically incorrect explanation.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}