Mstn
M. musculus
myostatin
What the model saw
Gene: Mstn Organism: Mus musculus Known functions: myostatin. growth/differentiation factor 8. cytokine activity. growth factor activity. heparin binding. identical protein binding. protein binding. protein homodimerization activity. protein serine/threonine kinase activator activity. signaling receptor binding.
View unredacted entry
myostatin. growth/differentiation factor 8. cytokine activity. growth factor activity. heparin binding. identical protein binding. protein binding. protein homodimerization activity. protein serine/threonine kinase activator activity. signaling receptor binding.
Solver output
Myostatin (GDF8) is a TGF-β superfamily member that acts as a negative regulator of skeletal muscle mass by activating SMAD2/3 signaling through ActRIIB/ALK4-5 receptors. Loss-of-function of Mstn in mice leads to dramatic muscle hypertrophy, improved metabolic profiles, and reduced adiposity, all of which are associated with extended healthspan. However, myostatin also promotes muscle atrophy and wasting (sarcopenia), a hallmark of aging, by suppressing satellite cell proliferation and differentiation, thereby contributing to stem cell exhaustion and muscle degeneration. Because Mstn's normal function is to inhibit muscle growth and promote atrophy/wasting, its activity is net anti-longevity; inhibiting Mstn is consistently associated with improved muscle maintenance, reduced frailty, and extended healthspan in mice. The protein serine/threonine kinase activator activity reflects its role in activating SMAD-dependent signaling cascades that suppress anabolic pathways including IGF-1/PI3K/Akt/mTOR in muscle.
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 mechanistic role of myostatin as a negative regulator of muscle mass that promotes sarcopenia and muscle wasting, and correctly concludes that Mstn's normal function is "net anti-longevity." However, the model then contradicts itself by outputting "pro_longevity" as the final prediction, which is the opposite of the ground truth "anti_longevity." The reasoning actually supports the correct answer (anti_longevity) but the final classification is wrong. The mechanism_class of "cellular_senescence" is also not the primary mechanism — it's more about muscle atrophy/sarcopenia and TGF-β signaling. The model's reasoning is internally inconsistent: it argues Mstn promotes atrophy and wasting (anti-longevity effects) but then labels it pro_longevity. This appears to be a confusion between the gene's effect and the effect of inhibiting the gene.
Raw API responses
solver
{
"reasoning": "Myostatin (GDF8) is a TGF-β superfamily member that acts as a negative regulator of skeletal muscle mass by activating SMAD2/3 signaling through ActRIIB/ALK4-5 receptors. Loss-of-function of Mstn in mice leads to dramatic muscle hypertrophy, improved metabolic profiles, and reduced adiposity, all of which are associated with extended healthspan. However, myostatin also promotes muscle atrophy and wasting (sarcopenia), a hallmark of aging, by suppressing satellite cell proliferation and differentiation, thereby contributing to stem cell exhaustion and muscle degeneration. Because Mstn's normal function is to inhibit muscle growth and promote atrophy/wasting, its activity is net anti-longevity; inhibiting Mstn is consistently associated with improved muscle maintenance, reduced frailty, and extended healthspan in mice. The protein serine/threonine kinase activator activity reflects its role in activating SMAD-dependent signaling cascades that suppress anabolic pathways including IGF-1/PI3K/Akt/mTOR in muscle.",
"confidence": 0.65,
"key_pathways": [
"TGF-β/SMAD2/3 signaling via ActRIIB",
"IGF-1/PI3K/Akt/mTOR muscle anabolism suppression",
"satellite cell proliferation and myogenesis inhibition"
],
"mechanism_class": "cellular_senescence",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identifies the mechanistic role of myostatin as a negative regulator of muscle mass that promotes sarcopenia and muscle wasting, and correctly concludes that Mstn's normal function is \"net anti-longevity.\" However, the model then contradicts itself by outputting \"pro_longevity\" as the final prediction, which is the opposite of the ground truth \"anti_longevity.\" The reasoning actually supports the correct answer (anti_longevity) but the final classification is wrong. The mechanism_class of \"cellular_senescence\" is also not the primary mechanism — it's more about muscle atrophy/sarcopenia and TGF-β signaling. The model's reasoning is internally inconsistent: it argues Mstn promotes atrophy and wasting (anti-longevity effects) but then labels it pro_longevity. This appears to be a confusion between the gene's effect and the effect of inhibiting the gene.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}