FGF21 connects ER stress to sulfide signaling to enhance cellular resilience.
Abstract
Fibroblast growth factor 21 (FGF21) is a stress-induced endocrine hormone that regulates metabolism. Grandl et al. show that FGF21, through its receptor β-klotho (KLB), enhances sulfide signaling and hydrogen sulfide production, strengthening the unfolded protein response and integrated stress response to promote stress resilience, metabolic adaptation, and potentially healthy aging.
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Research summary
FGF21 enhances cellular resilience and stress adaptation by linking ER stress to sulfide signaling through the KLB receptor. This work is relevant as it elucidates a specific molecular mechanism for stress resilience and metabolic adaptation, which are hallmarks of aging, though the direct translation to lifespan extension remains to be fully established.
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