Vitamin K2 Extends Lifespan by Alleviating Mitochondrial Stress via the <scp>JNK</scp> ‐1/ <scp>SIR</scp> ‐2.1/ <scp>DAF</scp> ‐16 Signaling Axis in <i>Caenorhabditis elegans</i>

Vitamin K2 is a fat-soluble vitamin that has been reported to exhibit significant anti-stress activity. Anti-stress properties are considered to be closely associated with lifespan extension. Therefore, we investigated the effects of vitamin K2 on the lifespan and stress resistance of Caenorhabditis elegans, as well as the underlying mechanisms. In the present study, we found that the effects of Vitamin K2 on C. elegans are concentration-dependent. High concentrations (10 μM) of Vitamin K2 are toxic to C. elegans, whereas lower concentrations (5 μM) are beneficial. Treatment with 5 μM Vitamin K2 can extend the lifespan of C. elegans, enhance its physiological functions, protect the intestinal barrier, and reduce the accumulation of lipofuscin associated with aging. Furthermore, Vitamin K2 enhanced the stress resistance of C. elegans by maintaining mitochondrial morphology, alleviating mitochondrial stress, reducing ROS levels, and improving mitochondrial membrane potential and ATP production. Vitamin K2 activates the JNK-1/SIR-2.1/DAF-16 signaling pathway and upregulates the expression of downstream target genes such as ctl-1, ctl-2, sod-1, sod-3, and hsp-16.2. We conclude that appropriate doses of Vitamin K2 protect C. elegans from senescence by activating the JNK-1/SIR-2.1/DAF-16-mediated anti-mitochondrial oxidative stress pathway. These findings suggest that Vitamin K2 may have beneficial effects on lifespan and mitochondrial health in C. elegans, providing a basis for further investigation into its potential relevance for aging and age-related diseases in more complex model systems.