alh-6
C. elegans
Aldehyde dehydrogenase domain-containing protein;L-glutamate gamma-semialdehyde dehydrogenase
What the model saw
Gene: alh-6 Organism: Caenorhabditis elegans Known functions: Aldehyde dehydrogenase domain-containing protein;L-glutamate gamma-semialdehyde dehydrogenase. L-glutamate gamma-semialdehyde dehydrogenase activity. oxidoreductase activity.
View unredacted entry
Aldehyde dehydrogenase domain-containing protein;L-glutamate gamma-semialdehyde dehydrogenase. L-glutamate gamma-semialdehyde dehydrogenase activity. oxidoreductase activity.
Solver output
ALH-6 encodes a mitochondrial aldehyde dehydrogenase with L-glutamate gamma-semialdehyde dehydrogenase activity, functioning in the proline catabolism pathway. It catalyzes the oxidation of L-glutamate gamma-semialdehyde (also known as pyrroline-5-carboxylate, P5C) to glutamate, a key step in proline degradation. Loss of alh-6 in C. elegans causes accumulation of P5C/reactive aldehydes in mitochondria, leading to mitochondrial stress and activation of the mitochondrial unfolded protein response (UPRmt). While UPRmt activation can be pro-longevity in some contexts, the primary function of ALH-6 is to prevent toxic aldehyde accumulation and maintain proline/glutamate metabolic flux, which supports mitochondrial integrity and redox homeostasis. Published studies in C. elegans show that alh-6 loss-of-function shortens lifespan under proline-rich dietary conditions, indicating the normal enzymatic activity of ALH-6 is required for longevity by preventing mitochondrial proteotoxic stress from aldehyde accumulation.
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 correctly predicted pro_longevity for alh-6 in C. elegans with high confidence (0.72). The mechanistic reasoning is detailed and accurate: ALH-6 functions in proline catabolism by converting L-glutamate gamma-semialdehyde (P5C) to glutamate, and loss of alh-6 leads to toxic aldehyde accumulation and mitochondrial stress. The model correctly notes that alh-6 loss-of-function shortens lifespan, making the wild-type gene pro-longevity. The mechanism classification as "deregulated_nutrient_sensing" is somewhat imprecise (mitochondrial stress/redox homeostasis would be more accurate), but the narrative reasoning is mechanistically sound and well-supported by published literature.
Raw API responses
solver
{
"reasoning": "ALH-6 encodes a mitochondrial aldehyde dehydrogenase with L-glutamate gamma-semialdehyde dehydrogenase activity, functioning in the proline catabolism pathway. It catalyzes the oxidation of L-glutamate gamma-semialdehyde (also known as pyrroline-5-carboxylate, P5C) to glutamate, a key step in proline degradation. Loss of alh-6 in C. elegans causes accumulation of P5C/reactive aldehydes in mitochondria, leading to mitochondrial stress and activation of the mitochondrial unfolded protein response (UPRmt). While UPRmt activation can be pro-longevity in some contexts, the primary function of ALH-6 is to prevent toxic aldehyde accumulation and maintain proline/glutamate metabolic flux, which supports mitochondrial integrity and redox homeostasis. Published studies in C. elegans show that alh-6 loss-of-function shortens lifespan under proline-rich dietary conditions, indicating the normal enzymatic activity of ALH-6 is required for longevity by preventing mitochondrial proteotoxic stress from aldehyde accumulation.",
"confidence": 0.72,
"key_pathways": [
"proline catabolism / P5C-glutamate conversion",
"mitochondrial redox homeostasis",
"mitochondrial unfolded protein response (UPRmt)"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for alh-6 in C. elegans with high confidence (0.72). The mechanistic reasoning is detailed and accurate: ALH-6 functions in proline catabolism by converting L-glutamate gamma-semialdehyde (P5C) to glutamate, and loss of alh-6 leads to toxic aldehyde accumulation and mitochondrial stress. The model correctly notes that alh-6 loss-of-function shortens lifespan, making the wild-type gene pro-longevity. The mechanism classification as \"deregulated_nutrient_sensing\" is somewhat imprecise (mitochondrial stress/redox homeostasis would be more accurate), but the narrative reasoning is mechanistically sound and well-supported by published literature.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}