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C60 in olive oil causes light-dependent toxicity and does not extend lifespan in mice

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Abstract

C60 is a potent antioxidant that has been reported to substantially extend the lifespan of rodents when formulated in olive oil (C60-OO) or extra virgin olive oil (C60-EVOO). Despite there being no regulated form of C60-OO, people have begun obtaining it from online sources and dosing it to themselves or their pets, presumably with the assumption of safety and efficacy. In this study, we obtain C60-OO from a sample of online vendors, and find marked discrepancies in appearance, impurity profile, concentration, and activity relative to pristine C60-OO formulated in-house. We additionally find that pristine C60-OO causes no acute toxicity in a rodent model but does form toxic species that can cause significant morbidity and mortality in mice in under 2 weeks when exposed to light levels consistent with ambient light. Intraperitoneal injections of C60-OO did not affect the lifespan of CB6F1 female mice. Finally, we conduct a lifespan and health span study in males and females C57BL/6 J mice comparing oral treatment with pristine C60-EVOO and EVOO alone versus untreated controls. We failed to observe significant lifespan and health span benefits of C60-EVOO or EVOO supplementation compared to untreated controls, both starting the treatment in adult or old age. Our results call into question the biological benefit of C60-OO in aging.

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References

  1. Huang YY, Sharma SK, Yin R, Agrawal T, Chiang LY, Hamblin MR. Functionalized fullerenes in photodynamic therapy. Journal of Biomedical Nanotechnology. 2014.

  2. Friedman SH, DeCamp DL, Kenyon GL, Sijbesma RP, Srdanov G, Wudl F. Inhibition of the HIV-1 Protease by Fullerene Derivatives: Model Building Studies and Experimental Verification. J Am Chem Soc. 1993

  3. Rouse JG, Yang J, Ryman-Rasmussen JP, Barron AR, Monteiro-Riviere NA. Effects of mechanical flexion on the penetration of fullerene amino acid-derivatized peptide nanoparticles through skin. Nano Lett. 2007.

  4. Maeda-Mamiya R, Noiri E, Isobe H, Nakanishi W, Okamoto K, Doi K, Sugaya T, Izumi T, Homma T, Nakamura E. In vivo gene delivery by cationic tetraamino fullerene. Proc Natl Acad Sci U S A. 2010.

  5. Zakharian TY, Seryshev A, Sitharaman B, Gilbert BE, Knight V, Wilson LJ. A fullerene-paclitaxel chemotherapeutic: synthesis, characterization, and study of biological activity in tissue culture. J Am Chem Soc. 2005.

  6. Liu J, Ohta Sichi, Sonoda A, Yamada M, Yamamoto M, Nitta N, Murata K, Tabata Y. Preparation of PEG-conjugated fullerene containing Gd3+ ions for photodynamic therapy. J Control Release. 2007.

  7. Markovic Z, Trajkovic V. Biomedical potential of the reactive oxygen species generation and quenching by fullerenes (C60). Biomaterials. 2008;29:3561–73.

    Article  CAS  Google Scholar 

  8. Okuda K, Mashino T, Hirobe M. Superoxide radical quenching and cytochrome C peroxidase-like activity of C60-dimalonic acid, C62(COOH)4. Bioorganic Med Chem Lett. 1996; .

  9. Wang IC, Tai LA, Lee DD, Kanakamma PP, Shen CKF, Luh TY, Cheng CH, Hwang KC. C60 and water-soluble fullerene derivatives as antioxidants against radical-initiated lipid peroxidation. J Med Chem. 1999.

  10. Yin JJ, Lao F, Fu PP, Wamer WG, Zhao Y, Wang PC, Qiu Y, Sun B, Xing G, Dong J, Liang XJ, Chen C. The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materials. Biomaterials. 2009.

  11. Santos SM, Dinis AM, Peixoto F, Ferreira L, Jurado AS, Videira RA. Interaction of fullerene nanoparticles with biomembranes: from the partition in lipid membranes to effects on mitochondrial bioenergetics. Toxicol Sci. 2014.

  12. Grebinyk A, Grebinyk S, Prylutska S, Ritter U, Matyshevska O, Dandekar T, Frohme M. C 60 fullerene accumulation in human leukemic cells and perspectives of LED-mediated photodynamic therapy. Free Radic Biol Med. 2018.

  13. Grebinyk A, Grebinyk S, Prylutska S, Ritter U, Matyshevska O, Dandekar T, Frohme M. HPLC-ESI-MS method for C60 fullerene mitochondrial content quantification. Data Br. 2018.

  14. Baati T, Bourasset F, Gharbi N, Njim L, Abderrabba M, Kerkeni A, Szwarc H, Moussa F. The prolongation of the lifespan of rats by repeated oral administration of [60]fullerene. Biomaterials [Internet]. Biomaterials; 2012 [cited 2020 Jun 1]; 33: 4936–46. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22498298

  15. Tsuchiya T, Oguri I, Yamakoshi YN, Miyata N. Novel harmful effects of [60]fullerene on mouse embryos in vitro and in vivo. FEBS Lett [Internet]. Elsevier B.V.; 1996 [cited 2020 Jul 24]; 393: 139–45. Available from: https://pubmed.ncbi.nlm.nih.gov/8804443/

  16. Aly FM, Othman A, Haridy MAM. Protective effects of fullerene C60 nanoparticles and virgin Olive oil against genotoxicity induced by cyclophosphamide in rats. Oxid Med Cell Longev [Internet]. Oxid Med Cell Longev; 2018 [cited 2020 Jul 24]; 2018: 1261356. Available from: https://pubmed.ncbi.nlm.nih.gov/30116471/

  17. Shershakova N, Baraboshkina E, Andreev S, Purgina D, Struchkova I, Kamyshnikov O, Nikonova A, Khaitov M. Anti-inflammatory effect of fullerene C60 in a mice model of atopic dermatitis. J Nanobiotechnology [Internet]. BioMed Central Ltd.; 2016 [cited 2020 Jul 24]; 14: 8. Available from: http://www.jnanobiotechnology.com/content/14/1/8

  18. Quick KL, Ali SS, Arch R, Xiong C, Wozniak D, Dugan LL. A carboxyfullerene SOD mimetic improves cognition and extends the lifespan of mice. Neurobiol Aging [Internet]. 2008 [cited 2017 Jan 16]; 29: 117–28. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17079053

  19. Taylor R, Parsons JP, Avent AG, Rannard SP, Dennis TJ, Hare JP, Kroto HW, Walton DRM. Degradation of C60 by light [Internet]. Nature. Nature Publishing Group; 1991 [cited 2020 Jul 23]. p. 277. Available from: https://www.nature.com/articles/351277a0

  20. Sun YP, Ma B, Bunker CE, Liu B. All-carbon polymers (polyfullerenes) from photochemical reactions of fullerene clusters in room-temperature solvent mixtures. J Am Chem Soc [Internet]. American Chemical Society; 1995 [cited 2020 Jul 23]; 117: 12705–11. Available from: https://pubs.acs.org/doi/abs/10.1021/ja00156a007

  21. Juha L, Krása J, Láska L, Hamplová V, Soukup L, Engst P, Kubát P. Fast degradation of fullerenes by ultraviolet laser radiation. Appl Phys B Photophysics Laser Chem [Internet]. Springer-Verlag; 1993 [cited 2020 Jul 23]; 57: 83–4. Available from: https://link.springer.com/article/10.1007/BF00324103

  22. Creegan KM, Robbins JL, Robbins WK, Millar JM, Sherwood RD, Tindall PJ, Cox DM, Smith AB, McCauley JP, Jones DR, Gallagher RT. Synthesis and characterization of C60O, the first fullerene epoxide. J Am Chem Soc [Internet]. American Chemical Society; 1992 [cited 2020 Jul 23]; 114: 1103–5. Available from: https://pubs.acs.org/doi/abs/10.1021/ja00029a058

  23. Deacon RMJ. Measuring the Strength of Mice. J Vis Exp [Internet]. 2013 [cited 2016 Nov 2]; . Available from: http://www.jove.com/video/2610/measuring-the-strength-of-mice

  24. Malavolta M, Basso A, Giacconi R, Orlando F, Pierpaoli E, Cardelli M, et al. Recovery from mild Escherichia coli O157:H7 infection in young and aged C57BL/6 mice with intact flora estimated by fecal shedding, locomotor activity and grip strength. Comp Immunol Microbiol Infect Dis. 2019;63:1–9.

    Article  Google Scholar 

  25. Malavolta M, Dato S, Villa F, De Rango F, Iannone F, Ferrario A, Maciag A, Ciaglia E, D’amato A, Carrizzo A, Basso A, Orlando F, Provinciali M, et al. LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice. Aging (Albany NY) [Internet]. 2019; 11: 6555–68. Available from: http://www.aging-us.com/article/102209/text?_escaped_fragment_=

  26. Duricki DA, Soleman S, Moon LDF. Analysis of longitudinal data from animals with missing values using SPSS. Nat Protoc. Nature Publishing Group. 2016;11:1112–29.

    Article  CAS  Google Scholar 

  27. Epstein J, Rosenthal RW, Ess RJ. Use of γ-(4-Nitrobenzyl)pyridine as analytical reagent for ethylenimines and alkylating agents. Anal Chem [Internet]. 1955; 27: 1435–9. Available from: https://pubs.acs.org/doi/abs/10.1021/ac60105a022

  28. Bystrzejewski M, Huczko A, Lange H, Drabik J, Pawelec E. Influence of C60 and fullerene soot on the oxidation resistance of vegetable oils. Fullerenes Nanotub Carbon Nanostructures. 2007.

  29. Krichene D, Allalout A, Mancebo-Campos V, Salvador MD, Zarrouk M, Fregapane G. Stability of virgin olive oil and behaviour of its natural antioxidants under medium temperature accelerated storage conditions. Food Chem. Elsevier. 2010;121:171–7.

    Article  CAS  Google Scholar 

  30. Velasco J, Dobarganes C. Oxidative stability of virgin olive oil. Eur J Lipid Sci Technol [Internet]. John Wiley & Sons, Ltd; 2002 [cited 2020 Jul 24]; 104: 661–76. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/1438-9312%28200210%29104%3A9/10%3C661%3A%3AAID-EJLT661%3E3.0.CO%3B2-D

  31. Basso A, Del Bello G, Piacenza F, Giacconi R, Costarelli L, Malavolta M. Circadian rhythms of body temperature and locomotor activity in aging BALB/c mice: early and late life span predictors. Biogerontology. 2016;17:703–14.

    Article  CAS  Google Scholar 

  32. Keil G, Cummings E, de Magalhães JP. Being cool: how body temperature influences ageing and longevity [Internet]. Biogerontology. Kluwer Academic Publishers; 2015 [cited 2020 Jul 23]. p. 383–97. Available from: https://link.springer.com/article/10.1007/s10522-015-9571-2

  33. Chistyakov VA, Smirnova YO, Prazdnova E V., Soldatov A V. Possible mechanisms of fullerene C60 antioxidant action. Biomed Res Int. 2013.

  34. Virruso C, Accardi G, Colonna-Romano G, Candore G, Vasto S, Caruso C. Nutraceutical properties of extra-virgin olive oil: a natural remedy for age-related disease? Rejuvenation Res [Internet]. Mary Ann Liebert Inc.; 2014 [cited 2020 Jul 24]; 17: 217–20. Available from: https://pubmed.ncbi.nlm.nih.gov/24219356/

  35. Rossi M, Caruso F, Kwok L, Lee G, Caruso A, Gionfra F, Candelotti E, Belli SL, Molasky N, Raley-Susman KM, Leone S, Filipský T, Tofani D, et al. Protection by extra virgin olive oil against oxidative stress in vitro and in vivo. Chemical and biological studies on the health benefits due to a major component of the Mediterranean diet. PLoS One [Internet]. Public Library of Science; 2017 [cited 2020 Jul 24]; 12. Available from: https://pubmed.ncbi.nlm.nih.gov/29283995/

  36. Ramot Y, Ben-Eliahu S, Kagan L, Ezov N, Nyska A. Subcutaneous and intraperitoneal lipogranulomas following subcutaneous injection of olive oil in Sprague-Dawley Rats. Toxicol Pathol [Internet]. Toxicol Pathol; 2009 [cited 2020 Jul 24]; 37: 882–6. Available from: https://pubmed.ncbi.nlm.nih.gov/19770348/

  37. Sun L, Sadighi Akha AA, Miller RA, Harper JM. Life-span extension in mice by preweaning food restriction and by methionine restriction in middle age. J Gerontol A Biol Sci Med Sci [Internet]. 2009 [cited 2020 Jul 24]; 64: 711–22. Available from: https://pubmed.ncbi.nlm.nih.gov/19414512/

  38. Hernandez-Pando, De La Luz Streber, Orozco, Arriaga, Pavon, Al-Nakhli, Rook. The effects of androstenediol and dehydroepiandrosterone on the course and cytokine profile of tuberculosis in BALB/c mice. Immunology [Internet]. John Wiley & Sons, Ltd; 1998 [cited 2020 Jul 31]; 95: 234–41. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2567.1998.00601.x

  39. Gao Y, Li X, Gao Q, Fan L, Jin H, Guo Y. Differential effects of olive oil, soybean oil, corn oil and lard oil on carbon tetrachloride-induced liver fibrosis in mice. Biosci Rep [Internet]. Portland Press Ltd; 2019 [cited 2020 Jul 31]; 39: 20191913. Available from: https://doi.org/10.1042/BSR20191913

  40. Cong W, Wang P, Qu Y, Tang J, Bai R, Zhao Y, Chen C, Bi X. Evaluation of the influence of fullerenol on aging and stress resistance using Caenorhabditis elegans. Biomaterials [Internet]. Elsevier Ltd; 2015 [cited 2020 Jul 24]; 42: 78–86. Available from: https://pubmed.ncbi.nlm.nih.gov/25542795/

  41. Quick KL, Ali SS, Arch R, Xiong C, Wozniak D, Dugan LL. A carboxyfullerene SOD mimetic improves cognition and extends the lifespan of mice. Neurobiol Aging. Neurobiol Aging. 2008;29:117–28.

    Article  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank SUNY ESF for support in the use of their facilities and Onondaga Community College (OCC) for the lending of equipment. This work was funded under a sponsored research agreement from BioSenex, Ltd., by Ricerca Corrente funding from Italian Ministry of Health to IRCCS INRCA, as well as through generous grants from Longecity.org and the Methuselah Foundation.

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Author notes

  1. Kelsey J. Moody and Marco Malavolta shared senior authorship.

Authors and Affiliations

  1. Ichor Therapeutics, Inc., 2521 US Route 11, LaFayette, NY, 13084, USA

    Kristopher J. Grohn, Brandon S. Moyer, Danique C. Wortel, Cheyanne M. Fisher, Ellie Lumen, Anthony H. Bianchi, Kathleen Kelly, Paul S. Campbell, Aaron J. Wolfe & Kelsey J. Moody

  2. Department of Chemistry, College of Environmental Science and Forestry, State University of New York, Syracuse, NY, 13210, USA

    Kristopher J. Grohn

  3. Betterhumans Inc., Gainesville, FL, USA

    Ellie Lumen & James Clement

  4. Department of Chemistry and Physical Sciences, State University of New York, Onondaga Community College, Syracuse, NY, 13215, USA

    Douglas E. Hagrman

  5. BioSenex, Ltd., Lyndhurst, 1 Cranmer Street, Nottingham, Nottinghamshire, NG10 1NJ, UK

    Roger G. Bagg

  6. Advanced Technology Center for Aging Research, IRCCS INRCA, via Birarelli 8, 60121, Ancona, Italy

    Andrea Basso, Cristina Nicoletti, Giovanni Lai, Mauro Provinciali & Marco Malavolta

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Correspondence to Marco Malavolta.

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The animal procedures followed the 2010/63/EU directive on the protection of animals used for scientific purposes and were approved by the Ethic Committee on Animal Use of INRCA.

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Grohn, K.J., Moyer, B.S., Wortel, D.C. et al. C60 in olive oil causes light-dependent toxicity and does not extend lifespan in mice. GeroScience 43, 579–591 (2021). https://doi.org/10.1007/s11357-020-00292-z

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