Original Articles

Anti-aging effects of deuterium-depleted water on Mn-induced toxicity in the Fibroblast cell model

Abstract

Objectives:  In recent decades, deuterium-depleted water (DDW) has been discussed as a supplement to increase the longevity. In this study we aim to investigate the effects of DDW on the factors involved in the aging process including FOXO gene family and oxidative stress. We also aim to study the effect of DDW on cellular toxicity caused by heavy metal of manganese.

Methods: We used HNNFPi8 cell line as an experimental model. HNNFPi8 cell line incubated with specific DDW media with deuterium concentration of 30ppm, 50ppm, 75ppm, 100ppm, 125ppm and 150ppm and 0.01 to 5mM MnCl2 up to 72 h. Cell proliferation, the activities of catalase and superoxide dismutase (SOD) antioxidant were determined by MTT and colorimetric methods, respectively.  RT-PCR was used to measure FOXO3A gene expression.

Results: The increase in MnCl2 concentration resulted in dose-dependently reduction in the viability of the cells. However, the decrease in the cell viability in the treated groups with DDW was found to be significantly lower in concentrations of 50ppm to 125 ppm DDW. DDW at concentrations of 30, 50, 75, 100 and 125 ppm could significantly upregulate the expression of FOXO3A gene in the cells treated with different concentrations of MnCl2. In addition, DDW at concentrations of 75, 100 and 125 ppm were able to increase the activities of these two antioxidant enzymes in the cells treated with different concentrations of MnCl2

Conclusion: The results suggest that DDW, especially at concentrations of 100 and 125ppm, is effective in reducing the toxic effects of the MnCl2.

1. Mitchell H, Hamilton T, Steggerda F, Bean H. The chemical composition of the adult human body and its bearing on the biochemistry of growth. Journal of Biological Chemistry. 1945;158(3):625-37.
2. Rundel PW, Ehleringer JR, Nagy KA. Stable isotopes in ecological research: Springer Science & Business Media; 2012.
3. Somlyai G, Jancsó G, Jákli G, Vass K, Barna B, Lakics V, et al. Naturally occurring deuterium is essential for the normal growth rate of cells. FEBS letters. 1993;317(1-2):1-4.
4. Huang C, Wikfeldt KT, Tokushima T, Nordlund D, Harada Y, Bergmann U, et al. Reply to Soper et al.: Fluctuations in water around a bimodal distribution of local hydrogen-bonded structural motifs. Proceedings of the National Academy of Sciences. 2010;107(12):E45-E.
5. Somlyai G, Laskay G, Berkényi T, Galbács Z, Galbács G, Kiss S, et al. The biological effects of deuterium-depleted water, a possible new tool in cancer therapy. Zeitschrift fur Onkologie. 1999;30:91-4.
6. Czajka DM, Finkel AJ. Effect of deuterium oxide on the reproductive potential of mice. Annals of the New York Academy of Sciences (US). 1960;84.
7. Ávila DS, Somlyai G, Somlyai I, Aschner M. Anti-aging effects of deuterium depletion on Mn-induced toxicity in a C. elegans model. Toxicology letters. 2012;211(3):319-24.
8. Wang Y, Zhou Y, Graves DT. FOXO transcription factors: their clinical significance and regulation. BioMed research international. 2014;2014(1):925350.
9. Calissi G, Lam EW-F, Link W. Therapeutic strategies targeting FOXO transcription factors. Nature reviews Drug discovery. 2021;20(1):21-38.
10. Zhang K, Qi C, Cai K. Manganese‐based tumor immunotherapy. Advanced Materials. 2023;35(19):2205409.
11. Budinger D, Barral S, Soo AK, Kurian MA. The role of manganese dysregulation in neurological disease: emerging evidence. The Lancet Neurology. 2021;20(11):956-68.
12. Liu K, Liu Z, Liu Z, Ma Z, Deng Y, Liu W, et al. Manganese induces S-nitrosylation of PINK1 leading to nerve cell damage by repressing PINK1/Parkin-mediated mitophagy. Science of The Total Environment. 2022;834:155358.
13. Guo J, Huang X, Dou L, Yan M, Shen T, Tang W, et al. Aging and aging-related diseases: from molecular mechanisms to interventions and treatments. Signal transduction and targeted therapy. 2022;7(1):391.
14. Du S, Zheng H. Role of FoxO transcription factors in aging and age-related metabolic and neurodegenerative diseases. Cell & bioscience. 2021;11(1):188.
15. Torigoe TH, Willcox DC, Shimabukuro M, Higa M, Gerschenson M, Andrukhiv A, et al. Novel protective effect of the FOXO3 longevity genotype on mechanisms of cellular aging in Okinawans. npj Aging. 2024;10(1):18.
16. Hardiany NS, Nurfiyana W, Iswanti FC. Polymorphism of the Forkhead box-O3 (FOXO3) Longevity Gene rs2802292 and senescence-associated secretory phenotype (SASP) in Indonesian Elderly Population. Nutrition and Healthy Aging. 2024;9(1):47-54.
17. Gupta S, Afzal M, Agrawal N, Almalki WH, Rana M, Gangola S, et al. Harnessing the FOXO-SIRT1 axis: insights into cellular stress, metabolism, and aging. Biogerontology. 2025;26(2):65.
18. Bayrak BB, Kulak GY, Yanardag R, Yarat A. Short term deuterium depletion in drinking water reduced tumor induced oxidative stress in mice liver. Pathology-Research and Practice. 2022;240:154186.
19. Funk WD, Wang CK, Shelton DN, Harley CB, Pagon GD, Hoeffler WK. Telomerase expression restores dermal integrity to in vitro-aged fibroblasts in a reconstituted skin model. Exp Cell Res. 2000;258(2):270-8.
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IssueVol 2 No 3 (2024) QRcode
SectionOriginal Articles
Keywords
Deuterium depleted water FOXO genes family Oxidative Stress aging manganese

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How to Cite
1.
Yavari K, Ashofteh M, Ghorbani Z. Anti-aging effects of deuterium-depleted water on Mn-induced toxicity in the Fibroblast cell model. ABI. 2024;2(3):146-154.