Skip to main content
SpringerLink
Log in

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

  • Research Article
  • Published:
Biogerontology Aims and scope Submit manuscript

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 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

SIV:

Shatavarin IV

DR:

Dietary restriction

GFP:

Green fluorescent protein

GST:

Glutathione-S-transferase

qRT-PCR:

Qualitative real time-polymerase chain reaction

References

  • Aladzsity I, Tóth ML, Sigmond T, Szabó E, Bicsák B, Barna J, Regős Á, Orosz L, Kovács AL, Vellai T (2007) Autophagy genes unc-51 and bec-1 are required for normal cell size in Caenorhabditis elegans. Genetics 177(1):655–660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alberti A, Michelet X, Djeddi A, Legouis R (2010) The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer formation and longevity in C. elegans. Autophagy 6(5):622–633

    Article  CAS  PubMed  Google Scholar 

  • Avery L, You YJ (2012) C. elegans feeding. WormBook First published May, 21.

  • Bar DZ, Charar C, Dorfman J, Yadid T, Tafforeau L, Lafontaine DL, Gruenbaum Y (2016) Cell size and fat content of dietary-restricted Caenorhabditis elegans are regulated by ATX-2, an mTOR repressor. Proc Natl Acad Sci 113:E4620–E4629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Belinha I, Amorim MA, Rodrigues P, de Freitas V, Moradas-Ferreira P, Mateus N, Costa V (2007) Quercetin increases oxidative stress resistance and longevity in Saccharomyces cerevisiae. J Agric Food Chem 55(6):2446–2451

    Article  CAS  PubMed  Google Scholar 

  • Biradar SP, Tamboli AS, Khandare RV, Pawar PK (2019) Chebulinic acid and Boeravinone B act as anti-aging and anti-apoptosis phyto-molecules during oxidative stress. Mitochondrion 46:236–246

    Article  CAS  PubMed  Google Scholar 

  • Bishop NA, Guarente L (2007a) Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 447(7144):545–549

    Article  CAS  PubMed  Google Scholar 

  • Bishop NA, Guarente L (2007b) Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 447:545–549

    Article  CAS  PubMed  Google Scholar 

  • Blackwell TK, Steinbaugh MJ, Hourihan JM, Ewald CY, Isik M (2015) SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans. Free Radical Biol Med 88:290–301

    Article  CAS  Google Scholar 

  • Brenner S (1974) The genetics of Caenorhabditis elegans. Genetics 77(1):71–94

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chamoli M, Singh A, Malik Y, Mukhopadhyay A (2014) A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans. Aging Cell 13(4):641–655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clokey GV, Jacobson LA (1986) The autofluorescent “lipofuscin granules” in the intestinal cells of Caenorhabditis elegans are secondary lysosomes. Mech Ageing Dev 35(1):79–94

    Article  CAS  PubMed  Google Scholar 

  • Díaz-Gómez R, López-Solís R, Obreque-Slier E, Toledo-Araya H (2013) Comparative antibacterial effect of gallic acid and catechin against Helicobacter pylori LWT-Food. Sci Technol 54:331–335

    Google Scholar 

  • Gems D (2016) What is aging?. In: Wynants M, Nuyttens G (eds) AGE-From The Anatomy Of Life To The Architecture Of Living. Crosstalks/VUBPress. https://www.ucl.ac.uk/~ucbtdag/Gems_2016. pdf (Erişim Tarihi: 11 Eylül 2017).

  • Gomez-Amaro RL et al (2015) Measuring food intake and nutrient absorption in Caenorhabditis elegans. Genetics 200:443–454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gruber J, Tang SY, Halliwell B (2007) Evidence for a trade-off between survival and fitness caused by resveratrol treatment of Caenorhabditis elegans. Ann N Y Acad Sci 1100:530–542

    Article  CAS  PubMed  Google Scholar 

  • Hammer C, Braum E (1988) Quantification of age pigments (lipofuscin). Compar Biochem Physiol Part B 90(1):7–17

    Article  CAS  Google Scholar 

  • Hands SL, Proud CG, Wyttenbach A (2009) mTOR's role in ageing: protein synthesis or autophagy? Aging 1(7):586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hansen M, Chandra A, Mitic LL, Onken B, Driscoll M, Kenyon C (2008) A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS Genet 4(2):24

    Article  CAS  Google Scholar 

  • Hercus MJ, Loeschcke V, Rattan SI (2003) Lifespan extension of Drosophila melanogaster through hormesis by repeated mild heat stress. Biogerontology 4(3):149–156

    Article  CAS  PubMed  Google Scholar 

  • Hosono R (1978) Sterilization and growth inhibition of Caenorhabditis elegans by 5-fluorodeoxyuridine. Exp Gerontol 13(5):369–373

    Article  CAS  PubMed  Google Scholar 

  • Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300(5622):1142–1145

    Article  CAS  PubMed  Google Scholar 

  • Ighodaro OM, Akinloye OA (2018) First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): their fundamental role in the entire antioxidant defence grid. Alexandria J Med 54(4):287–293

    Article  Google Scholar 

  • Irving BA, Weltman JY, Brock DW, Davis CK, Gaesser GA, Weltman A (2007) NIH ImageJ and Slice-O-Matic computed tomography imaging software to quantify soft tissue. Obesity 15(2):370–376

    Article  PubMed  Google Scholar 

  • Itoh K et al (1997) An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 236:313–322

    Article  CAS  PubMed  Google Scholar 

  • Kenyon C (2010a) A pathway that links reproductive status to lifespan in Caenorhabditis elegans. Ann N Y Acad Sci 1204:156–162

    Article  CAS  PubMed  Google Scholar 

  • Kenyon CJ (2010b) The genetics of ageing. Nature 464(7288):504–512

    Article  CAS  PubMed  Google Scholar 

  • Kim YC, Guan KL (2015) mTOR: a pharmacologic target for autophagy regulation. J Clin Investig 125(1):25–32

    Article  PubMed  PubMed Central  Google Scholar 

  • Li J, Zhang CX, Liu YM, Chen KL, Chen G (2017) A comparative study of anti-aging properties and mechanism: resveratrol and caloric restriction. Oncotarget 8(39):65717

    Article  PubMed  PubMed Central  Google Scholar 

  • Lithgow GJ, White TM, Melov S, Johnson TE (1995) Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci 92(16):7540–7544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mair W, Dillin A (2008) Aging and survival: the genetics of life span extension by dietary restriction. Annu Rev Biochem 77:727–754

    Article  CAS  PubMed  Google Scholar 

  • Masclaux-Daubresse C, Chen Q, Havé M (2017) Regulation of nutrient recycling via autophagy. Curr Opin Plant Biol 39:8–17

    Article  CAS  PubMed  Google Scholar 

  • McKay JP, Raizen DM, Gottschalk A, Schafer WR, Avery L (2004a) eat-2 and eat-18 are required for nicotinic neurotransmission in the Caenorhabditis elegans pharynx. Genetics 166(1):161–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McKay JP, Raizen DM, Gottschalk A, Schafer WR, Avery L (2004b) eat-2 and eat-18 are required for nicotinic neurotransmission in the Caenorhabditis elegans pharynx. Genetics 166:161–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meléndez A, Tallóczy Z, Seaman M, Eskelinen EL, Hall DH, Levine B (2003) Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301(5638):1387–1391

    Article  PubMed  CAS  Google Scholar 

  • Mitra SK, Prakash NS, Sundaram R (2012) Shatavarins (containing Shatavarin IV) with anticancer activity from the roots of Asparagus racemosus. Indian J Pharmacol 44(6):732

    Article  PubMed  PubMed Central  Google Scholar 

  • Munoz MJ (2003) Longevity and heat stress regulation in Caenorhabditis elegans. Mech Ageing Dev 124(1):43–48

    Article  CAS  PubMed  Google Scholar 

  • Nakamura S, Yoshimori T (2018) Autophagy and longevity. Mol Cells 41(1):65

    CAS  PubMed  PubMed Central  Google Scholar 

  • Oberhauser KS (1997) Fecundity, lifespan and egg mass in butterflies: effects of male-derived nutrients and female size. Funct Ecol 11(2):166–175

    Article  Google Scholar 

  • Olsen A, Vantipalli MC, Lithgow GJ (2006) Using Caenorhabditis elegans as a model for aging and age-related diseases. Ann NY Acad Sci 1067(1):120–128

    Article  CAS  PubMed  Google Scholar 

  • Panowski SH, Wolff S, Aguilaniu H, Durieux J, Dillin A (2007) PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans. Nature 447(7144):550–555

    Article  CAS  PubMed  Google Scholar 

  • Pant A, Pandey R (2015) Bioactive phytomolecules and aging in Caenorhabditis elegans. Healthy Aging Research 4:1–15

    Google Scholar 

  • Park SK, Tedesco PM, Johnson TE (2009) Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1. Aging Cell 8(3):258–269

    Article  CAS  PubMed  Google Scholar 

  • Raizen D, Song BM, Trojanowski N, You YJ (2018) Methods for measuring pharyngeal behaviors. In: WormBook: The Online Review of C. elegans Biology [Internet]. WormBook.

  • Raizen DM, Lee R, Avery L (1995) Interacting genes required for pharyngeal excitation by motor neuron MC in Caenorhabditis elegans. Genetics 141:1365–1382

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rathor L, Akhoon BA, Pandey S, Srivastava S, Pandey R (2015) Folic acid supplementation at lower doses increases oxidative stress resistance and longevity in Caenorhabditis elegans. Age 37:113

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rathor L, Pandey R (2018) Age-induced diminution of free radicals by Boeravinone B in Caenorhabditis elegans. Exp Gerontol 111:94–106

    Article  CAS  PubMed  Google Scholar 

  • Robida-Stubbs S, Glover-Cutter K, Lamming DW, Mizunuma M, Narasimhan SD, Neumann-Haefelin E, Sabatini DM, Blackwell TK (2012) TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell Metab 15(5):713–724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruck A, Attonito J, Garces KT, Núnez L, Palmisano NJ, Rubel Z, Bai Z, Nguyen KC, Sun L, Grant BD, Hall DH (2011) The Atg6/Vps30/Beclin 1 ortholog BEC-1 mediates endocytic retrograde transport in addition to autophagy in C. elegans. Autophagy 7(4):386–400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protocols 3(6):1101–1108

    Article  CAS  PubMed  Google Scholar 

  • Shailaja M, Gowda KD, Vishakh K, Kumari NS (2017) Anti-aging role of curcumin by modulating the inflammatory markers in albino wistar rats. J Natl Med Assoc 109(1):9–13

    Article  PubMed  Google Scholar 

  • Sheaffer KL, Updike DL, Mango SE (2008) The Target of Rapamycin pathway antagonizes pha-4/FoxA to control development and aging. Curr Biol 18(18):1355–1364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smita SS, Raj Sammi S, Laxman TS, Bhatta RS, Pandey R (2017) Shatavarin IV elicits lifespan extension and alleviates Parkinsonism in Caenorhabditis elegans. Free Radical Res 51(11–12):954–969

    Article  CAS  Google Scholar 

  • Smith-Vikos T, de Lencastre A, Inukai S, Shlomchik M, Holtrup B, Slack FJ (2014) MicroRNAs mediate dietary-restriction-induced longevity through PHA-4/FOXA and SKN-1/Nrf transcription factors. Curr Biol 24(19):2238–2246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Srivastava D, Arya U, Soundara Rajan T, Dwivedi H, Kumar S, Subramaniam JR (2008) Reserpine can confer stress tolerance and lifespan extension in the nematode C. elegans. Biogerontology 9(5):309–316

    Article  CAS  PubMed  Google Scholar 

  • Srivastava S, Sammi SR, Laxman TS, Pant A, Nagar A, Trivedi S, Bhatta RS, Tandon S, Pandey R (2017) Silymarin promotes longevity and alleviates Parkinson’s associated pathologies in Caenorhabditis elegans. Journal of functional foods 31:32–43

    Article  CAS  Google Scholar 

  • Staab TA, Griffen TC, Corcoran C, Evgrafov O, Knowles JA, Sieburth D (2013) The conserved SKN-1/Nrf2 stress response pathway regulates synaptic function in Caenorhabditis elegans. PLoS Genet 9(3):1003354

    Article  CAS  Google Scholar 

  • Steinkraus KA, Smith ED, Davis C, Carr D, Pendergrass WR, Sutphin GL, Kennedy BK, Kaeberlein M (2008) Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans. Aging Cell 7(3):394–404

    Article  CAS  PubMed  Google Scholar 

  • Suryanto D, Nasution SK, Munir E (2012) Antimicrobial activity of some bacterial isolates from Sibolangit Natural Recreational Park of north Sumatra, Indonesia. Bull Environ Pharmacol Life Sci 1:01–07

    Google Scholar 

  • Terman A, Brunk UT (1998) Lipofuscin: mechanisms of formation and increase with age. Apmis 106(1–6):265–276

    Article  CAS  PubMed  Google Scholar 

  • Tissenbaum HA (2015) Using C. elegans for aging research. Invertebr Reprod Dev 59(1):59–63

    Article  PubMed  Google Scholar 

  • Trivedi S, Pandey R (2020) 5′-Hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone extends longevity mediated by DR-induced autophagy and oxidative stress resistance in C. elegans. GeroScience 1:1. https://doi.org/10.1007/s11357-020-00229-6

    Article  CAS  Google Scholar 

  • Walker G, Houthoofd K, Vanfleteren JR, Gems D (2005) Dietary restriction in C. elegans: from rate-of-living effects to nutrient sensing pathways. Mech Ageing Dev 126(9):929–937

    Article  CAS  PubMed  Google Scholar 

  • Wang D, Xing X (2008) Assessment of locomotion behavioral defects induced by acute toxicity from heavy metal exposure in nematode Caenorhabditis elegans. Journal of Environmental Sciences 20:1132–1137

    Article  CAS  Google Scholar 

  • Wang N, Luo Z, Jin M, Sheng W, Wang HT, Long X, Wu Y, Hu P, Xu H, Zhang X (2019) Exploration of age-related mitochondrial dysfunction and the anti-aging effects of resveratrol in zebrafish retina. Aging (Albany NY) 11(10):3117

    Article  CAS  Google Scholar 

  • Weithoff G (2007) Dietary restriction in two rotifer species: the effect of the length of food deprivation on life span and reproduction. Oecologia 153(2):303–308

    Article  PubMed  Google Scholar 

  • Yen K, Le TT, Bansal A, Narasimhan SD, Cheng J-X, Tissenbaum HA (2010) A comparative study of fat storage quantitation in nematode Caenorhabditis elegans using label and label-free methods. PLoS ONE 5:e12810

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

The authors are highly grateful to Director CSIR-CIMAP, Lucknow for his encouragement. Nematode strains employed in this study were provided by the Caenorhabditis Genetics Center (CGC) University of Minnesota, MN, USA, funded by the NIH National Center for Research Resources (NCRR). Authors are thankful to Prof Shashi Pandey, Department of Botany, Centre for Advanced Studies, BHU, Varanasi, for her editorial help. The senior author also thanks the University Grants Commission for Research Fellowship.

Author information

Authors and Affiliations

  1. Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, Lucknow, 226015, India

    Shachi Shuchi Smita, Shalini Trivedi, Taruna Pandey, Mashu Trivedi & Rakesh Pandey

Authors
  1. Shachi Shuchi Smita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shalini Trivedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Taruna Pandey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mashu Trivedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rakesh Pandey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rakesh Pandey.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file 1 (DOCX 25 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Smita, S.S., Trivedi, S., Pandey, T. et al. A Bioactive compound Shatavarin IV-mediated longevity as revealed by dietary restriction-induced autophagy in Caenorhabditis elegans. Biogerontology 21, 827–844 (2020). https://doi.org/10.1007/s10522-020-09897-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-020-09897-5

Keywords

Search

Navigation