LAUSR

Abstract Neoagarotetraose (NAT) has been reported to ameliorate aging-associated diseases. The present study found that NAT extended the lifespan of Caenorhabditis (C.) elegans up to 21.9% and improved resistance to stresses of heat and oxidation. Moreover, using a series of C. elegans mutants, insulin/insulin-like signaling (IIS) was found to be involved in NAT mediated lifespan extension. Meanwhile, the extended lifespan by NAT was in part via AMP-activated protein kinase (AMPK), which further enhanced the activity of DAF-16. NAT could lower ATP levels and act as a mimic of dietary restriction (DR) as evidenced by the involvement of nutrient sensing pathways, such as IIS, AMPK, and target of rapamycin (TOR). Moreover, NAT induced autophagy both in worms and in human embryonic lung fibroblast cells. Taken together, NAT could be potentially used as a DR mimic centered on AMPK. The results from this study provide new evidence for anti-aging effect of NAT in C. elegnas and insights into implication of anti-aging activity of NAT in higher organisms.