Life Extension Magazine

Life Extension Magazine August 2013

Report

Three-Step Strategy to Reverse Mitochondrial Aging

By Michael Downey

References

  1. Lanza IR, Nair KS. Mitochondrial function as a determinant of life span. Pflugers Arch. 2010 Jan;459(2):277-89.
  2. Robb EL, Page MM, Stuart JA. Mitochondria, cellular stress resistance, somatic cell depletion and lifespan. Curr Aging Sci. 2009 Mar;2(1):12-27.
  3. Alexeyev MF, LeDoux SP, Wilson GL. Mitochondrial DNA and aging. Clin Sci (Lond). 2004 Oct;107(4):355-64.
  4. Wei YH, Lu CY, Lee HC, Pang CY, Ma YS. Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of mitochondrial respiratory function. Ann NY Acad Sci. 1998 Nov 20;854:155-70.
  5. Mandavilli BS, Santos JH, Van Houten B. Mitochondrial DNA repair and aging. Mutat Res. 2002 Nov 30;509(1-2):127-51.
  6. Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med. 2000 Aug;29(3-4):222-30.
  7. Wei YH, Lee HC. Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp Biol Med (Maywood). 2002 Oct;227(9):671-82.
  8. Hamilton ML, Van Remmen H, Drake JA, et al. Does oxidative damage to DNA increase with age? PNAS. 2001;98(18):10469-74.
  9. Conley KE, Marcinek DJ, Villarin J. Mitochondrial dysfunction and age. Curr Opin Clin Nutr Metab Care. 2007 Nov;10(6):688-92.
  10. Barja G. Free radicals and aging. Trends Neurosci. 2004 Oct;27(10):595-600.
  11. Hekimi S, Lapointe J, Wen Y. Taking a “good” look at free radicals in the aging process. Trends Cell Biol. 2011 Oct;21(10):569-76.
  12. Liochev SI. Reactive oxygen species and the free radical theory of aging. Free Radic Biol Med. 2013 Jul;60:1-4.
  13. Sinha K, Das J, Pal PB, Sil PC. Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol. 2013 Mar 30. [Epub ahead of print]
  14. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J. 2012 Jan;5(1):9-19.
  15. Kumar A, Pant MC, Singh HS, Khandelwal S. Determinants of oxidative stress and DNA damage (8-OhdG) in squamous cell carcinoma of head and neck. Indian J Cancer. 2012 Jul-Sep;49(3):309-15.
  16. Berquist BR, Wilson DM 3rd. Pathways for repairing and tolerating the spectrum of oxidative DNA lesions. Cancer Lett. 2012 Dec 31;327(1-2):61-72.
  17. Barja G. Updating the Mitochondrial Free Radical Theory of Aging: An integrated view, key aspects, and confounding concepts. Antioxid Redox Signal. 2013 May 5. [Epub ahead of print]
  18. Neustadt J, Pieczenik SR. Medication-induced mitochondrial damage and disease. Mol Nutr Food Res. 2008 Jul;52(7):780-8.
  19. Linnane AW, Marzuki S, Ozawa T, Tanaka M. Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet. 1989;1(8639):642-5.
  20. Rolo AP, Palmeira CM. Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol. 2006 Apr 15;212(2):167-78.
  21. Picard M, Turnbull DM. Linking the metabolic state and mitochondrial DNA in chronic disease, health, and aging. Diabetes. 2013 Mar;62(3):672-8.
  22. Scheffler K, Krohn M, Dunkelmann T, et al. Mitochondrial DNA polymorphisms specifically modify cerebral β-amyloid proteostasis. Acta Neuropathol. 2012 Aug;124(2):199-208.
  23. Maruszak A, Zekanowski C. Mitochondrial dysfunction and Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Mar 30;35(2):320-30.
  24. De Pauw A, Tejerina S, Raes M, Keijer J, Arnould T. Mitochondrial (dys)function in adipocyte (de)differentiation and systemic metabolic alterations. Am J Pathol. 2009 Sep;175(3):927-39.
  25. Short KR, Bigelow ML, Kahl J, et al. Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci USA. 2005 Apr 12;102(15):5618-23.
  26. Linnane AW, Kovalenko S, Gingold EB. The universality of bioenergetic disease: age-associated cellular bioenergetic degradation and amelioration therapy. Ann N Y Acad Sci. 1998 Nov 20;854:202-13.
  27. Karbowski M, Neutzner A. Neurodegeneration as a consequence of failed mitochondrial maintenance. Acta Neuropathol. 2012 Feb;123(2):157-71.
  28. Duberley KE, Abramov AY, Chalasani A, Heales SJ, Rahman S, Hargreaves IP. Human neuronal coenzyme Q10 deficiency results in global loss of mitochondrial respiratory chain activity, increased mitochondrial oxidative stress and reversal of ATP synthase activity: implications for pathogenesis and treatment. J Inherit Metab Dis. 2013 Jan;36(1):63-73.
  29. Fernández-Ayala DJ, López-Lluch G, García-Valdés M, Arroyo A, Navas P. Specificity of coenzyme Q10 for a balanced function of respiratory chain and endogenous ubiquinone biosynthesis in human cells. Biochim Biophys Acta. 2005;1706:174-83.
  30. López-Martín JM, Salviati L, Trevisson E, et al. Missense mutation of the COQ2 gene causes defects of bioenergetics and de novo pyrimidine synthesis. Hum Mol Genet. 2007;16:1091-7.
  31. Cordero MD, Cotán D, del-Pozo-Martín Y, et al. Oral coenzyme Q10 supplementation improves clinical symptoms and recovers pathologic alterations in blood mononuclear cells in a fibromyalgia patient. Nutrition. 2012 Nov-Dec;28(11-12):1200-3.
  32. Takahashi M, Ogawara M, Shimizu T, Shirasawa T. Restoration of the behavioral rates and lifespan in clk-1 mutant nematodes in response to exogenous coenzyme Q(10). Exp Gerontol. 2012 Mar;47(3):276-9.
  33. Ishii N, Senoo-Matsuda N, Miyake K, et al. Coenzyme Q10 can prolong C. elegans lifespan by lowering oxidative stress. Mech Ageing Dev. 2004 Jan;125(1):41-6.
  34. Quiles JL, Ochoa JJ, Huertas JR, Mataix J. Coenzyme Q supplementation protects from age-related DNA double-strand breaks and increases lifespan in rats fed on a PUFA-rich diet. Exp Gerontol. 2004 Feb;39(2):189-94.
  35. Available at: http://www.cdc.gov/nchs/fastats/lifexpec.htm. Accessed May 14, 2013.
  36. Schmelzer C, Kohl C, Rimbach G, Doring F. The reduced form of coenzyme Q10 decreases the expression of lipopolysaccharide-sensitive genes in human THP-1 cells. J Med Food. 2011 Apr;14(4):391-7.
  37. Santos-Gonzalez M, Gomez Diaz C, Navas P, Villalba JM. Modifications of plasma proteome in long-lived rats fed on a coenzyme Q10-supplemented diet. Exp Gerontol. 2007 Aug;42(8):798-806.
  38. Lee BJ, Huang YC, Chen SJ, Lin PT. Effects of coenzyme Q10 supplementation on inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, and homocysteine) in patients with coronary artery disease. Nutrition. 2012 Jul;28(7-8):767-72.
  39. McGowan PO, Kato T. Epigenetics in mood disorders. Environ Health Prev Med. 2008 Jan;13(1):16-24.
  40. Wadsworth TL, Bishop JA, Pappu AS, Woltjer RL, Quinn JF. Evaluation of coenzyme Q as an antioxidant strategy for Alzheimer’s disease. J Alzheimers Dis. 2008 Jun;14(2):225-34.
  41. Moreira PI, Santos MS, Sena C, Nunes E, Seica R, Oliveira CR. CoQ10 therapy attenuates amyloid beta-peptide toxicity in brain mitochondria isolated from aged diabetic rats. Exp Neurol. 2005 Nov;196(1):112-9.
  42. Yang X, Yang Y, Li G, Wang J, Yang ES. Coenzyme Q10 attenuates beta-amyloid pathology in the aged transgenic mice with Alzheimer presenilin 1 mutation. J Mol Neurosci. 2008 Feb;34(2):165-71.
  43. Forester BP, Zuo CS, Ravichandran C, et al. Coenzyme Q10 effects on creatine kinase activity and mood in geriatric bipolar depression. J Geriatr Psychiatry Neurol. 2012 Mar;25(1):43-50.
  44. Gvozdjáková A, Kucharská J, Bartkovjaková M, Gazdíková K, Gazdík FE. Coenzyme Q10 supplementation reduces corticosteroids dosage in patients with bronchial asthma. Biofactors. 2005;25(1-4):235-40.
  45. Fujimoto S, Kurihara N, Hirata K, Takeda T. Effects of coenzyme Q10 administration on pulmonary function and exercise performance in patients with chronic lung diseases. Clin Investig. 1993;71(8 Suppl):S162-6.
  46. Mezawa M, Takemoto M, Onishi S, et al. The reduced form of coenzyme Q10 improves glycemic control in patients with type 2 diabetes: an open label pilot study. Biofactors. 2012 Nov-Dec;38(6):416-21.
  47. El-ghoroury EA, Raslan HM, Badawy EA, et al. Malondialdehyde and coenzyme Q10 in platelets and serum in type 2 diabetes mellitus: correlation with glycemic control. Blood Coagul Fibrinolysis. 2009 Jun;20(4):248-51.
  48. Hodgson JM, Watts GF, Playford DA, Burke V, Croft KD. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr. 2002 Nov;56(11):1137-42.
  49. Sander S, Coleman CI, Patel AA, Kluger J, White CM. The impact of coenzyme Q10 on systolic function in patients with chronic heart failure. J Card Fail. 2006 Aug;12(6):464-72.
  50. Dai YL, Luk TH, Yiu KH, et al. Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: a randomized controlled trial. Atherosclerosis. 2011 Jun;216(2):395-401.
  51. Mikhin VP, Kharchenko AV, Rosliakova EA, Cherniatina MA. Application of coenzyme Q(10) in combination therapy of arterial hypertension. Kardiologiia. 2011;51(6):26-31.
  52. Yang X, Dai G, Li G, Yang ES. Coenzyme Q10 reduces beta-amyloid plaque in an APP/PS1 transgenic mouse model of Alzheimer’s disease. J Mol Neurosci . 2010 May;41(1):110-3.
  53. Dumont M, Kipiani K, Yu F, et al. Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis. 2011;27(1):211-23.
  54. Alehagen U, Johansson P, Bjornstedt M, Rosen A, Dahlstrom U. Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: A 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. Int J Cardiol. 2012 May 22.
  55. Mortensen SA, et al. Coenzyme Q10: clinical benefits with biochemical correlates suggesting a scientific breakthrough in the management of chronic heart failure. Int J Tissue React. 1990;12(3):155-62.
  56. Lenaz G, Bovina C, D’Aurelio M, et al. Role of mitochondria in oxidative stress and aging. Ann N Y Acad Sci. 2002 Apr;959:199-213.
  57. Misra HS, Rajpurohit YS, Khairnar NP. Pyrroloquinoline-quinone and its versatile roles in biological processes. J Biosci. 2012 Jun;37(2):313-25.
  58. Steiner JL, Murphy EA, McClellan JL, Carmichael MD, Davis JM. Exercise training increases mitochondrial biogenesis in the brain. J Appl Physiol. 2011 Oct;111(4):1066-71.
  59. Guarente L. Mitochondria--a nexus for aging, calorie restriction, and sirtuins? Cell. 2008 Jan 25;132(2):171-6.
  60. Rucker R, Chowanadisai W, Nakano M. Potential physiological importance of pyrroloquinoline quinone. Altern Med Rev. 2009 Sep;14(3):268-77.
  61. Choi O, Kim J, Kim JG, et al. Pyrroloquinoline quinone is a plant growth promotion factor produced by Pseudomonas fluorescens B16. Plant Physiol. 2008 Feb;146(2):657-68.
  62. Stites T, Storms D, Bauerly K, et al. Tchaparian. Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice. J Nutr. 2006 Feb;136(2):390-6.
  63. Steinberg F, Stites TE, Anderson P, et al. Pyrroloquinoline quinone improves growth and reproductive performance in mice fed chemically defined diets. Exp Biol Med (Maywood). 2003 Feb;228(2):160-6.
  64. Bauerly KA, Storms DH, Harris CB, et al. Pyrroloquinoline quinone nutritional status alters lysine metabolism and modulates mitochondrial DNA content in the mouse and rat. Biochim Biophys Acta. 2006 Nov;1760(11):1741-8.
  65. Urakami T, Yoshida C, Akaike T, Maeda H, Nishigori H, Niki E. Synthesis of monoesters of pyrroloquinoline quinone and imidazopyrroloquinoline, and radical scavenging activities using electron spin resonance in vitro and pharmacological activity in vivo. J Nutr Sci Vitaminol (Tokyo). 1997 Feb;43(1):19-33.
  66. Tchaparian E, Marshal L, Cutler G, et al. Identification of transcriptional networks responding to pyrroloquinoline quinone dietary supplementation and their influence on thioredoxin expression, and the JAK/STAT and MAPK pathways. Biochem J. 2010 Aug 1;429(3):515-26.
  67. Zhang JJ, Zhang RF, Meng XK. Protective effect of pyrroloquinoline quinone against Abeta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. Neurosci Lett. 2009 Oct 30;464(3):165-9.
  68. Kim J, Kobayashi M, Fukuda M, et al. Pyrroloquinoline quinone inhibits the fibrillation of amyloid proteins. Prion. 2010 Jan;4(1):26-31.
  69. Kobayashi M, Kim J, Kobayashi N, et al. Pyrroloquinoline quinone (PQQ) prevents fibril formation of alpha-synuclein. Biochem Biophys Res Commun. 2006 Oct 27;349(3):1139-44.
  70. Nakano M, Ubukata K, Yamamoto T, Yamaguchi H. Effect of pyrroloquinoline quinone (PQQ) on mental status of middle-aged and elderly persons. FOOD Style 21. 2009;13(7):50-3.
  71. Zhu BQ, Simonis U, Cecchini G, et al. Comparison of pyrroloquinoline quinone and/or metoprolol on myocardial infarct size and mitochondrial damage in a rat model of ischemia/reperfusion injury. J Cardiovasc Pharmacol Ther. 2006 Jun;11(2):119-28.
  72. Tao R, Karliner JS, Simonis U, et al. Pyrroloquinoline quinone preserves mitochondrial function and prevents oxidative injury in adult rat cardiac myocytes. Biochem Biophys Res Commun. 2007 Nov 16;363(2):257-62.
  73. Smidt CR, Bean-Knudsen D, Kirsch DG, Rucker RB. Does the intestinal microflora synthesize pyrroloquinoline quinone? Biofactors.1991 Jan;3(1):53-9.
  74. Zhang Y, Rosenberg PA. The essential nutrient pyrroloquinoline quinone may act as a neuroprotectant by suppressing peroxynitrite formation. Eur J Neurosci. 2002 Sep;16(6):1015-24.
  75. Schepetkin IA, Xie G, Jutila MA, Quinn MT. Complement-fixing activity of fulvic acid from Shilajit and other natural sources. Phytother Res. 2009 Mar;23(3):373-84.
  76. Goel RK, Banerjee RS, Acharya SB. Antiulcerogenic and antiinflammatory studies with shilajit. J Ethnopharmacol. 1990 Apr;29(1):95-103.
  77. Agarwal SP, Khanna R, Karmarkar R, Anwer MK, Khar RK. Shilajit: a review. Phytother Res. 2007 May;21(5):401-5.
  78. Ghosal S. Shilajit in Perspective. Oxford, U.K.: Narosa Publishing House; 2006.
  79. Islam A, Ghosh R, Banerjee D, Nath P, Mazumder U, Ghosal S. Biotransformation of 3-hydroxydibenzo-pyrone into 3,8 dihydroxydibenzo-pyrone and aminoacyl conjugates by Aspergillus niger isolated from native “shilajit.” Electro J Biotechno. 2008 Jul 15;11(3):2-10.
  80. Bhattacharyya S, Pal D, Gupta AK, Ganguly P, Majumder UK, Ghosal S. Beneficial effect of processed shilajit on swimming exercise induced impaired energy status of mice. Pharmacologyonline. 2009;1:817-25.
  81. Bhattacharyya S, Pal D, Banerjee D, et al. Shilajit dibenzo—pyrones: Mitochondria targeted antioxidants. Pharmacologyonline. 2009; 2:690-8.
  82. Kang SH, Choi W. Oxidative degradation of organic compounds using zero-valent iron in the presence of natural organic matter serving as an electron shuttle. Environ Sci Technol. 2009 Feb 1;43(3):878-83.
  83. Visser SA. Effect of humic substances on mitochondrial respiration and oxidative phosphorylation. Sci Total Environ. 1987 Apr;62:347-54.
  84. Pal D, Bhattacharya S. Pilot Study on the Improvement of Human Performance with ReVitalETTM as Energy Booster: Part-IV. 2006. Data on file. Natreon, Inc.
  85. Montero R, Grazina M, López-Gallardo E, et al. Coenzyme Q10 deficiency in mitochondrial DNA depletion syndromes. Mitochondrion. 2013 Apr 11.
  86. Available at: http://rarediseasesnetwork.epi.usf.edu/NAMDC/learnmore/diseases.htm. Accessed May 15, 2013.
  87. Age difference of bioavailability. Unpublished data, Kaneka Corp.
  88. Hosoe K, Kitano M, Kishida H, et al. Study on safety and bioavailability of ubiquinol (Kaneka QH(trade mark)) after single and 4-week multiple oral administration to healthy volunteers. Regul Toxicol Pharmacol. 2006 Aug 17.
  89. Shults CW, Oakes D, Kieburtz K, et al. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol. 2002 Oct;59(10):1541-50.
  90. Shults CW, Flint BM, Song D, Fontaine D. Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson’s disease. Exp Neurol. 2004 Aug;188(2):491-4.
  91. Kurowska EM, Dresser G, Deutsch L, Bassoo E, Freeman DJ. Relative bioavailability and antioxidant potential of two coenzyme q10 preparations. Ann Nutr Metab. 2003;47(1):16-21.
  92. Shults CW, Haas RH, Beal MF. A possible role of coenzyme Q10 in the etiology and treatment of Parkinson’s disease. Biofactors. 1999;9(2-4):267-72.