mrps-5
C. elegans
Small ribosomal subunit protein uS5m
What the model saw
Gene: mrps-5 Organism: Caenorhabditis elegans Known functions: Small ribosomal subunit protein uS5m. RNA binding. structural constituent of ribosome.
View unredacted entry
Small ribosomal subunit protein uS5m. RNA binding. structural constituent of ribosome.
Solver output
mrps-5 encodes the mitochondrial small ribosomal subunit protein uS5m, which is required for translation of mitochondrially-encoded OXPHOS subunits. Paradoxically, partial knockdown of mitochondrial ribosomal proteins in C. elegans — including mrps-5 — has been shown to extend lifespan by mildly impairing mitochondrial translation, reducing electron transport chain activity, and triggering the mitochondrial unfolded protein response (UPRmt). This mild mitochondrial stress activates compensatory longevity pathways (e.g., ATFS-1/UPRmt signaling), a well-characterized pro-longevity mechanism in worms. Thus, reduced mrps-5 function, rather than its full activity, promotes longevity, but the gene's normal role in sustaining mitochondrial ribosome integrity places it centrally in mitochondrial biogenesis and function.
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 identifies the mechanism (partial knockdown of mrps-5 extends lifespan via UPRmt/mitochondrial stress signaling) but arrives at the wrong classification. The ground truth labels mrps-5 as "anti_longevity," meaning the gene's normal function suppresses longevity (i.e., its knockdown extends lifespan). The model's reasoning actually describes this exact scenario — that reduced mrps-5 function promotes longevity — but then incorrectly classifies the gene as "pro_longevity." In GenAge's framework, a gene whose loss-of-function extends lifespan is classified as "anti_longevity" (the gene normally works against longevity). The model conflated "knockdown extends lifespan" with "pro_longevity," when the correct interpretation is "anti_longevity." The mechanistic reasoning is sound and accurate, but the final classification label is wrong.
Raw API responses
solver
{
"reasoning": "mrps-5 encodes the mitochondrial small ribosomal subunit protein uS5m, which is required for translation of mitochondrially-encoded OXPHOS subunits. Paradoxically, partial knockdown of mitochondrial ribosomal proteins in C. elegans — including mrps-5 — has been shown to extend lifespan by mildly impairing mitochondrial translation, reducing electron transport chain activity, and triggering the mitochondrial unfolded protein response (UPRmt). This mild mitochondrial stress activates compensatory longevity pathways (e.g., ATFS-1/UPRmt signaling), a well-characterized pro-longevity mechanism in worms. Thus, reduced mrps-5 function, rather than its full activity, promotes longevity, but the gene's normal role in sustaining mitochondrial ribosome integrity places it centrally in mitochondrial biogenesis and function.",
"confidence": 0.78,
"key_pathways": [
"mitochondrial unfolded protein response (UPRmt / ATFS-1)",
"mitochondrial translation / OXPHOS biogenesis",
"mitochondrial ribosome small subunit assembly"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identifies the mechanism (partial knockdown of mrps-5 extends lifespan via UPRmt/mitochondrial stress signaling) but arrives at the wrong classification. The ground truth labels mrps-5 as \"anti_longevity,\" meaning the gene's normal function suppresses longevity (i.e., its knockdown extends lifespan). The model's reasoning actually describes this exact scenario — that reduced mrps-5 function promotes longevity — but then incorrectly classifies the gene as \"pro_longevity.\" In GenAge's framework, a gene whose loss-of-function extends lifespan is classified as \"anti_longevity\" (the gene normally works against longevity). The model conflated \"knockdown extends lifespan\" with \"pro_longevity,\" when the correct interpretation is \"anti_longevity.\" The mechanistic reasoning is sound and accurate, but the final classification label is wrong.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}