[β-sitosterol, an important component in the fruits of Miq., prolongs lifespan of by suppressing the ferroptosis pathway].

OBJECTIVES

To elucidate the anti-aging effect of β-sitosterol (BS), an important component in the fruits of Miq., in and its regulatory effect on ETS-5 gene to modulate ferroptosis.

METHODS

treated with 10 µg/mL BS were monitored for survival time and changes in body length, motility, and reproductive function. The effect of ETS-5 gene knockdown on survival time of was observed, and the changes in fat accumulation and lipid redox homeostasis in the transfected were assessed using Oil Red O staining and by detecting MDA levels and the GSH/GSSG ratio. The mRNA expression levels of ferroptosis-related genes (FTN-1, GPX-1 and AAT-9) were detected using qPCR. The effects of BS treatment and ETS-5 knockdown on AAT-9 enzyme activity in were examined. The effect of BS on nuclear localization of FEV (the human homolog of ETS-5) was validated in cultured human umbilical venous endothelial cells (HUVECs).

RESULTS

Both BS treatment and ETS-5 knockdown significantly prolonged the lifespan, promoted lipid accumulation and reduced lipid peroxidation in . ETS-5 knockdown resulted in upregulated expressions of the ferroptosis repressors GPX-1, AAT-9 and FTN-1 and increased the GSH/GSSG ratio in .

CONCLUSIONS

BS inhibits ferroptosis in by suppressing the expression of ETS-5 transcription factor and hence the activity of AAT-9 enzyme, a key gene for ferroptosis, which in turn prolongs the lifespan of .