Hsp26
D. melanogaster
Heat shock protein 26
What the model saw
Gene: Hsp26 Organism: Drosophila melanogaster Known functions: Heat shock protein 26. heat shock protein 26. myosin binding. protein binding. protein folding chaperone. unfolded protein binding.
View unredacted entry
Heat shock protein 26. heat shock protein 26. myosin binding. protein binding. protein folding chaperone. unfolded protein binding.
Solver output
Hsp26 is a small heat shock protein (sHSP) in Drosophila melanogaster that functions as a molecular chaperone, binding unfolded or misfolded proteins and preventing their aggregation. By holding denatured client proteins in a folding-competent state and facilitating their refolding (often in cooperation with Hsp70/Hsp90 systems), Hsp26 directly maintains proteostasis — a central hallmark of aging. Overexpression of small HSPs in Drosophila has been shown to extend lifespan, consistent with the general principle that enhanced chaperone capacity buffers the accumulation of proteotoxic aggregates that drive aging. Its myosin-binding activity also suggests a role in maintaining muscle proteostasis, which is particularly relevant to age-related muscle decline (sarcopenia) in flies. Loss of proteostasis is a well-established driver of aging, and Hsp26's normal function directly counteracts this hallmark.
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 Hsp26 in Drosophila melanogaster. The mechanistic reasoning is sound and well-articulated: Hsp26 is a small heat shock protein that maintains proteostasis by preventing protein aggregation and facilitating refolding, which is a well-established pro-longevity mechanism. The model correctly notes that overexpression of small HSPs in Drosophila extends lifespan, and appropriately connects the myosin-binding activity to muscle proteostasis. The confidence level of 0.78 is appropriate given the strong mechanistic basis. Overall, this is an excellent prediction with correct answer and correct mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "Hsp26 is a small heat shock protein (sHSP) in Drosophila melanogaster that functions as a molecular chaperone, binding unfolded or misfolded proteins and preventing their aggregation. By holding denatured client proteins in a folding-competent state and facilitating their refolding (often in cooperation with Hsp70/Hsp90 systems), Hsp26 directly maintains proteostasis — a central hallmark of aging. Overexpression of small HSPs in Drosophila has been shown to extend lifespan, consistent with the general principle that enhanced chaperone capacity buffers the accumulation of proteotoxic aggregates that drive aging. Its myosin-binding activity also suggests a role in maintaining muscle proteostasis, which is particularly relevant to age-related muscle decline (sarcopenia) in flies. Loss of proteostasis is a well-established driver of aging, and Hsp26's normal function directly counteracts this hallmark.",
"confidence": 0.78,
"key_pathways": [
"proteostasis/chaperone network",
"heat shock response",
"unfolded protein refolding"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Hsp26 in Drosophila melanogaster. The mechanistic reasoning is sound and well-articulated: Hsp26 is a small heat shock protein that maintains proteostasis by preventing protein aggregation and facilitating refolding, which is a well-established pro-longevity mechanism. The model correctly notes that overexpression of small HSPs in Drosophila extends lifespan, and appropriately connects the myosin-binding activity to muscle proteostasis. The confidence level of 0.78 is appropriate given the strong mechanistic basis. Overall, this is an excellent prediction with correct answer and correct mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}