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

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RESEARCH ARTICLE

A Bioactive compound Shatavarin IV-mediated longevity as revealed by dietary restriction-induced autophagy in Caenorhabditis elegans Shachi Shuchi Smita . Shalini Trivedi . Taruna Pandey . Mashu Trivedi . Rakesh Pandey

Received: 27 May 2020 / Accepted: 26 August 2020 Ó Springer Nature B.V. 2020

Abstract 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

Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10522-020-09897-5) contains supplementary material, which is available to authorized users. S. S. Smita  S. Trivedi  T. Pandey  M. Trivedi  R. Pandey (&) Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, Lucknow 226015, India e-mail: [email protected]

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. Keywords Shatavarin IV  Longevity  Dietary restriction  Autophagy  C. elegans Abbreviations SIV Shatavarin IV DR Dietary restriction GFP Green fluorescent protein GST Glutathione-S-transferase qRTQualitative real time-polymerase chain PCR reaction

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Biogerontology

Introduction Aging is a time-dependent deterioration of functional capacity, regulatory mechanism, and stress resistance, associated with an increased chance of morbidity. Sometimes individual