A Bioactive compound Shatavarin IV-mediated longevity as revealed by dietary restriction-induced autophagy in...

Plant-based dietary supplements that delay aging are of significant interest now a days because these naturally occurring bioactive molecules effectively provide pharmaceuticals/neutraceuticals to deal with diseases related to the advanced life expectancy. In this paper, we aimed to investigate the effect of Shatavarin IV (SIV), a steroidal saponin isolated from Asparagus racemosus Willd. on dietary restriction (DR) induced longevity in Caenorhabditis elegans. SIV significantly increased the lifespan to 18% which is independent of antimicrobial activity and reduced the aging by-product, lipofuscin along with increased locomotion, and chemotaxis behavior in wild type worms. The longevity effect has been dependent on eat-2, which was further validated via reduced pharyngeal pumping rate that established the effect similar to DR induced longevity. Moreover, like eat-2 mutant worms, SIV reduces the total progeny number of wild type worm along with a significant alleviation of stored fat, which reconfirms the involvement of eat-2 mediated longevity. Further, it was also observed that DR induced longevity mechanism by SIV requires mTOR which works in PHA-4/FOXA dependent manner. In addition to this, the role of autophagy mechanism concerning SIV mediated DR was confirmed via bec-1, unc-51, and lgg-1. The longevity effect achieved by SIV was also dependent on SKN-1/NRF-2 and partially dependent on DAF-16/FOXO. Furthermore, the DR-induced longevity by SIV was found to be independent of hsf-1 exhibiting non-significant alteration in the mRNA expression of downstream target genes hsp-16.2 and hsp-70. Altogether, this study provides first-hand information on the pro-longevity effect of SIV in worms that have been mediated by the DR-regulating gene induced autophagy.