Targeting Mitochondrial Stress Responses: Terbinafine and Miglustat as Novel Lifespan and Healthspan Modulators

Terbinafine and miglustat are identified as novel mitochondrial stress inducers that extend lifespan and improve healthspan in Caenorhabditis elegans.

• Both compounds activate the mitochondrial stress response and exhibit distinct mechanisms of action.
• Terbinafine and miglustat activate the mitochondrial unfolded protein response mediator ATFS-1 and upregulate mitochondrial stress response pathways.
• These compounds modulate mitochondrial function across species, similarly to doxycycline.
• Terbinafine and miglustat engage the insulin/IGF-1 signaling pathway in C. elegans, suggesting an integrated stress response.
• Experiments in human HEK293T cells confirmed that both compounds induce mitochondrial stress and modulate mitochondrial function in mammalian systems.

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