Msra
M. musculus
methionine sulfoxide reductase A
What the model saw
Gene: Msra Organism: Mus musculus Known functions: methionine sulfoxide reductase A. mitochondrial peptide methionine sulfoxide reductase. L-methionine (S)-S-oxide reductase activity. peptide-methionine (S)-S-oxide reductase activity.
View unredacted entry
methionine sulfoxide reductase A. mitochondrial peptide methionine sulfoxide reductase. L-methionine (S)-S-oxide reductase activity. peptide-methionine (S)-S-oxide reductase activity.
Solver output
Msra encodes methionine sulfoxide reductase A (MsrA), which catalyzes the stereospecific reduction of L-methionine (S)-S-oxide back to methionine in both free amino acids and oxidized peptides/proteins. This enzymatic repair activity directly counteracts oxidative damage to proteins caused by reactive oxygen species (ROS), which accumulate with age. By restoring methionine residues in proteins, MsrA maintains proteostasis and prevents the accumulation of oxidatively damaged, dysfunctional proteins. The mitochondrial localization is particularly relevant, as mitochondria are a primary source of ROS and are especially vulnerable to oxidative protein damage. Loss of Msra in mice has been shown to reduce lifespan and increase oxidative stress, while overexpression extends lifespan in model organisms (e.g., Drosophila), firmly establishing its pro-longevity role through the oxidative stress repair arm of proteostasis maintenance.
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 Msra with high confidence (0.88). The mechanistic reasoning is accurate and detailed: MsrA reduces oxidized methionine residues, counteracting ROS-induced protein damage, with particular relevance in mitochondria. The model correctly notes that Msra knockout reduces lifespan and overexpression extends lifespan in Drosophila. The mechanism classification as "loss_of_proteostasis" is reasonable, though one could argue it's more directly an oxidative stress defense mechanism — but proteostasis maintenance is a valid framing since protein repair is a key component of proteostasis. Overall, excellent reasoning quality.
Raw API responses
solver
{
"reasoning": "Msra encodes methionine sulfoxide reductase A (MsrA), which catalyzes the stereospecific reduction of L-methionine (S)-S-oxide back to methionine in both free amino acids and oxidized peptides/proteins. This enzymatic repair activity directly counteracts oxidative damage to proteins caused by reactive oxygen species (ROS), which accumulate with age. By restoring methionine residues in proteins, MsrA maintains proteostasis and prevents the accumulation of oxidatively damaged, dysfunctional proteins. The mitochondrial localization is particularly relevant, as mitochondria are a primary source of ROS and are especially vulnerable to oxidative protein damage. Loss of Msra in mice has been shown to reduce lifespan and increase oxidative stress, while overexpression extends lifespan in model organisms (e.g., Drosophila), firmly establishing its pro-longevity role through the oxidative stress repair arm of proteostasis maintenance.",
"confidence": 0.88,
"key_pathways": [
"methionine sulfoxide reduction / oxidative protein repair",
"mitochondrial ROS defense",
"proteostasis maintenance"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Msra with high confidence (0.88). The mechanistic reasoning is accurate and detailed: MsrA reduces oxidized methionine residues, counteracting ROS-induced protein damage, with particular relevance in mitochondria. The model correctly notes that Msra knockout reduces lifespan and overexpression extends lifespan in Drosophila. The mechanism classification as \"loss_of_proteostasis\" is reasonable, though one could argue it's more directly an oxidative stress defense mechanism — but proteostasis maintenance is a valid framing since protein repair is a key component of proteostasis. Overall, excellent reasoning quality.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}