Homocysteine (Hcy) in humans represents a blood-borne biomarker which predicts the risk of age-related diseases and mortality. Using the nematode Caenorhabditis elegans, we tested whether feeding betaine-rich sugar beet molasses affects the survival under heat stress in the presence of Hcy, in spite of a gene loss in betaine–homocysteine methyltransferase.
Knockdown of the genes relevant for remethylation or transsulfuration of Hcy was achieved by RNA interference (RNAi). Survival assay was conducted under heat stress at 37 °C and Hcy levels were determined by enzyme-linked immunosorbent assay.
Addition of 500 mg/l betaine-rich sugar beet molasses (SBM) prevented the survival reduction that was caused by exposure to Hcy at 37 °C. Although SBM was no longer capable of reducing Hcy levels under RNAi versus homologues for 5, 10-methylenetetrahydrofolate reductase or cystathionine-β-synthase, it still enabled the survival extension by SBM under exposure to Hcy. In contrast, RNAi for the small heat shock protein hsp-16.2 or the foxo transcription factor daf-16 both prevented the extension of survival by betaine-rich molasses in the presence of Hcy.
Our studies demonstrate that betaine-rich SBM is able to prevent survival reduction caused by Hcy in C. elegans in dependence on hsp-16.2 and daf-16 but independent of the remethylation pathway.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
sugar beet molasses
Boldyrev AA (2009) Molecular mechanisms of homocysteine toxicity. Biochemistry 74(6):589–598
Haynes WG (2002) Hyperhomocysteinemia, vascular function and atherosclerosis: effects of vitamins. Cardiovasc Drugs Ther 16(5):391–399
Seshadri S, Beiser A, Selhub J, Jacques PF et al (2002) Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 346(7):476–483
Bonetti F, Brombo G, Zuliani G (2016) The relationship between hyperhomocysteinemia and neurodegeneration. Neurodegener Dis Manag 6(2):133–145. https://doi.org/10.2217/nmt-2015-0008
Barron E, Lara J, White M, Mathers JC (2015) Blood-borne biomarkers of mortality risk: systematic review of cohort studies. PLoS One 10(6):e0127550. https://doi.org/10.1371/journal.pone.0127550.eCollection2015
Masud R, Baqai HZ (2017) The communal relation of MTHFR, MTR, ACE gene polymorphisms and hyperhomocysteinemia as conceivable risk of coronary artery disease. Appl Physiol Nutr Metab 42(10):1009–1014. https://doi.org/10.1139/apnm-2017-0030
Liew SC, Gupta ED (2015) Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet 58(1):1–10. https://doi.org/10.1016/j.ejmg.2014.10.004
McRae MP (2013) Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis. J Chiropr Med 12(1):20–25. https://doi.org/10.1016/j.jcm.2012.11.001
Bito T, Watanabe F (2016) Biochemistry, function, and deficiency of vitamin B12 in Caenorhabditis elegans. Exp Biol Med (Maywood) 241(15):1663–1668. https://doi.org/10.1177/1535370216662713
Leiteritz A, Dilberger B, Wenzel U, Fitzenberger E (2018) Betaine reduces β-amyloid-induced paralysis through activation of cystathionine-β-synthase in an Alzheimer model of Caenorhabditis elegans. Genes Nutr 13:21. https://doi.org/10.1186/s12263-018-0611-9
Bartke A (2011) Single-gene mutations and healthy ageing in mammals. Philos Trans R Soc Lond B Biol Sci 366(1561):28–34. https://doi.org/10.1098/rstb.2010.0281
Brenner S (1974) The genetics of Caenorhabditis elegans. Genetics 77(1):71–94
Stiernagel T (2006) Maintenance of C. elegans. WormBook, ed. The C. elegans Research Community. Worm Book 11:1–11. https://doi.org/10.1895/wormbook.1.101.1
Lehner B, Tischler J, Fraser AG (2006) RNAi screens in Caenorhabditis elegans in a 96-well liquid format and their application to the systematic identification of genetic interactions. Nat Protoc 1(3):1617–1620. https://doi.org/10.1038/nprot.2006.245
Timmons L, Court D, Fire A (2001) Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene 263(1–2):103–112
Gill MS, Olsen A, Sampayo JN, Lithgow GJ (2003) An automated high-throughput assay for survival of the nematode Caenorhabditis elegans. Free Radic Biol Med 35:558–565
Wierzbicki AS (2007) Homocysteine and cardiovascular disease: a review of the evidence. Diabetes Vasc Dis Res 4(2):143–150
Parnetti L, Bottiglieri T, Lowenthal D (1997) Role of homocysteine in age-related vascular and non-vascular diseases. Aging 9(4):241–257
McCully KS (2009) Chemical pathology of homocysteine. IV. Excitotoxicity, oxidative stress, endothelial dysfunction, and inflammation. Ann Clin Lab Sci 39(3):219–232
Parkhitko AA, Binari R, Zhang N, Asara JM et al (2016) Tissue-specific down-regulation of S-adenosyl-homocysteine via suppression of dAhcyL1/dAhcyL2 extends health span and life span in Drosophila. Genes Dev 30(12):1409–1422. https://doi.org/10.1101/gad.282277.116
Craig SA (2004) Betaine in human nutrition. Am J Clin Nutr 80(3):539–549. https://doi.org/10.1093/ajcn/80.3.539
Finkelstein JD, Martin JJ (1984) Methionine metabolism in mammals. Distribution of homocysteine between competing pathways. J Biol Chem 259(15):9508–9513
Gregory JF, DeRatt BN, Rios-Avila L, Ralat M, Stacpoole PW (2016) Vitamin B6 nutritional status and cellular availability of pyridoxal 5′-phosphate govern the function of the transsulfuration pathway’s canonical reactions and hydrogen sulfide production via side reactions. Biochimie 126:21–26. https://doi.org/10.1016/j.biochi.2015.12.020
Módis K, Coletta C, Asimakopoulou A, Szczesny B et al (2014) Effect of S-adenosyl-l-methionine (SAM), an allosteric activator of cystathionine-β-synthase (CBS) on colorectal cancer cell proliferation and bioenergetics in vitro. Nitric Oxide 41:146–156. https://doi.org/10.1016/j.niox.2014.03.001
Shakeri M, Cottrell JJ, Wilkinson S, Ringuet M et al (2018) Betaine and antioxidants improve growth performance, breast muscle development and ameliorate thermoregulatory responses to cyclic heat exposure in broiler chickens. Animals (Basel) 25(8):E162. https://doi.org/10.3390/ani8100162
Giriş M, Doğru-Abbasoğlu S, Soluk-Tekkeşin M, Olgaç V, Uysal M (2018) Effect of betaine treatment on the regression of existing hepatic triglyceride accumulation and oxidative stress in rats fed on high fructose diet. Gen Physiol Biophys 37:563–570. https://doi.org/10.4149/gpb_2018005
Peden AS, Mac P, Fei YJ, Castro C et al (2013) Betaine acts on a ligand-gated ion channel in the nervous system of the nematode C. elegans. Nat Neurosci 16(12):1794–1801. https://doi.org/10.1038/nn.3575
Urban N, Tsitsipatis D, Hausig F, Kreuzer K et al (2017) Non-linear impact of glutathione depletion on C. elegans life span and stress resistance. Redox Biol 11:502–515. https://doi.org/10.1016/j.redox.2016.12.003
Rea SL, Wu D, Cypser JR, Vaupel JW, Johnson TE (2005) A stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegans. Nat Genet 37(8):894–898. https://doi.org/10.1038/ng1608
Murphy CT, McCarroll SA, Bargmann CI, Fraser A et al (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424(6946):277–283. https://doi.org/10.1038/nature01789
Conflict of interest
The authors declare that no conflict of interest exists.
About this article
Cite this article
Drobny, A., Meloh, H., Wächtershäuser, E. et al. Betaine-rich sugar beet molasses protects from homocysteine-induced reduction of survival in Caenorhabditis elegans. Eur J Nutr 59, 779–786 (2020). https://doi.org/10.1007/s00394-019-01944-3
- Caenorhabditis elegans
- Heat shock proteins