Figure 5.

(a) C8‐SA inhibits the eIF4H drr‐2 that acts downstream of TOR in worms and (b) reduces S6 phosphorylation in pNHEK and (c & d) induces autophagy as measured by the LC3‐II/LC3‐I ratio in pNHEK in a dose‐dependent manner. The induction of autophagy by 100 μM was actually found to be superior to that observed in response to exposure to 100 nM of rapamycin. In addition, C8‐SA (e) activates autophagy as detected by LGG‐1::GFP levels in hypodermal cells during the L3 stage. (f) Addition of C8‐SA failed to induce lifespan extension in worms in which bec‐1/beclin levels were downregulated. Similarly, the lifespan of worms in which the transcription factor hlh‐30 was either downregulated (g) or upregulated (h) was insensitive to C8‐SA. Taken together, these results strongly suggest that C8‐SA alters lifespan by modulating autophagy levels