Skip to main content

Advertisement

SpringerLink
Log in

Coenzyme Q10 supplementation reverses age-related impairments in spatial learning and lowers protein oxidation

  • Published:
AGE Aims and scope Submit manuscript

Abstract

Coenzyme Q10 (CoQ) is widely available as a dietary supplement and remains under consideration as a treatment for age-associated neurodegenerative conditions. However, no studies have determined if supplementation, initiated relatively late in life, could have beneficial effects on mild functional impairments associated with normal brain aging. Accordingly, the current study assessed the effect of CoQ intake in older mice for which cognitive and psychomotor impairments were already evident. Separate groups of young (3.5 months) and relatively old mice (17.5 months) were fed a control diet or a diet supplemented with low (0.72 mg/g) or high (2.81 mg/g) concentrations of CoQ for 15 weeks. After 6 weeks, the mice were given tests for spatial learning (Morris water maze), spontaneous locomotor activity, motor coordination, and startle reflex. Age-related impairments in cognitive and psychomotor functions were evident in the 17.5-month-old mice fed the control diet, and the low-CoQ diet failed to affect any aspect of the impaired performance. However, in the Morris water maze test, old mice on the high-CoQ diet swam to the safe platform with greater efficiency than the mice on the control diet. The old mice supplemented with the high-CoQ diet did not show improvement when spatial performance was measured using probe trials and failed to show improvement in other tests of behavioral performance. Protein oxidative damage was decreased in the mitochondria from the heart, liver, and skeletal muscle of the high-CoQ-supplemented mice and, to some extent, in the brain mitochondria. Contrasting with the deleterious effect of long-term CoQ supplementation initiated during young adulthood previously published, this study suggests that CoQ improves spatial learning and attenuates oxidative damage when administered in relatively high doses and delayed until early senescence, after age-related declines have occurred. Thus, in individuals with age-associated symptoms of cognitive decline, high-CoQ intake may be beneficial.

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

Similar content being viewed by others

References

  • Arcos JC, Sohal RS et al (1968) Changes in ultrastructure and respiratory control in mitochondria of rat heart hypertrophied by exercise. Exp Mol Pathol 8:49–65

    Article  PubMed  CAS  Google Scholar 

  • Baggio E, Gandini R et al (1993) Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure (interim analysis). The CoQ10 Drug Surveillance Investigators. Clin Investig 71(8 Suppl):S145–149

    PubMed  CAS  Google Scholar 

  • Battino M, Ferri E et al (1990) Natural distribution and occurrence of coenzyme Q homologues. Membr Biochem 9(3):179–190

    Article  PubMed  CAS  Google Scholar 

  • Beal MF (1999) Coenzyme Q10 administration and its potential for treatment of neurodegenerative diseases. Biofactors 9(2–4):261–266

    Article  PubMed  CAS  Google Scholar 

  • Beal MF, Henshaw DR et al (1994) Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate. Ann Neurol 36(6):882–888

    Article  PubMed  CAS  Google Scholar 

  • Bickford PC, Gould T et al (2000) Antioxidant-rich diets improve cerebellar physiology and motor learning in aged rats. Brain Res 866:211–217

    Article  PubMed  CAS  Google Scholar 

  • Bresolin N, Doriguzzi C et al (1990) Ubidecarenone in the treatment of mitochondrial myopathies: a multi-center double-blind trial. J Neurol Sci 100(1–2):70–78

    Article  PubMed  CAS  Google Scholar 

  • Burke SN, Barnes CA (2006) Neural plasticity in the ageing brain. Nat Rev Neurosci 7(1):30–40

    Article  PubMed  CAS  Google Scholar 

  • Cadoni G, Scipione S et al (2007) Coenzyme Q 10 and cardiovascular risk factors in idiopathic sudden sensorineural hearing loss patients. Otol Neurotol 28(7):878–883

    PubMed  Google Scholar 

  • Crane FL (2001) Biochemical functions of coenzyme Q10. J Am Coll Nutr 20(6):591–598

    Article  PubMed  CAS  Google Scholar 

  • de Fiebre NC, Sumien N et al (2006) Spatial learning and psychomotor performance of C57BL/6 mice: age sensitivity and reliability of individual differences. AGE 28(3):235–253

    Article  PubMed  Google Scholar 

  • Ernster L, Dallner G (1995) Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271(1):195–204

    Article  PubMed  Google Scholar 

  • Erway LC, Willot JF et al (1993) Genetics of age-related hearing loss in mice: I. Inbred and F1 hybrid strains. Hear Res 65:125–132

    Article  PubMed  CAS  Google Scholar 

  • Ferrante RJ, Andreassen OA et al (2002) Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease. J Neurosci 22(5):1592–1599

    PubMed  CAS  Google Scholar 

  • Ferrante KL, Shefner J et al (2005) Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS. Neurology 65(11):1834–1836

    Article  PubMed  CAS  Google Scholar 

  • Fetoni AR, Piacentini R et al (2009) Water-soluble Coenzyme Q10 formulation (Q-ter) promotes outer hair cell survival in a guinea pig model of noise induced hearing loss (NIHL). Brain Res 1257:108–116

    Article  PubMed  CAS  Google Scholar 

  • Fontaine E, Eriksson O et al (1998) Regulation of the permeability transition pore in skeletal muscle mitochondria. Modulation by electron flow through the respiratory chain complex. J Biol Chem 273(20):12662–12668

    Article  PubMed  CAS  Google Scholar 

  • Forsmark-Andree P, Dallner G et al (1995) Endogenous ubiquinol prevents protein modification accompanying lipid peroxidation in beef heart submitochondrial membranes. Free Radic Biol Med 19:749–757

    Article  PubMed  CAS  Google Scholar 

  • Forster MJ, Lal H (1991) Neurobehavioral biomarkers of aging: influence of genotype and dietary restriction. Biomed Environ Sci 4(1–2):144–165

    PubMed  CAS  Google Scholar 

  • Forster MJ, Lal H (1992) Within-subject behavioral analysis of recent memory in aging mice. Behav Pharmacol 3(4):337–349

    Article  PubMed  Google Scholar 

  • Forster MJ, Lal H (1999) Estimating age-related changes in psychomotor function: influence of practice and of level of caloric intake in different genotypes. Neurobiol Aging 20(2):167–176

    Article  PubMed  CAS  Google Scholar 

  • Forster MJ, Dubey A et al (1996) Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain. Proc Natl Acad Sci U S A 93(10):4765–4769

    Article  PubMed  CAS  Google Scholar 

  • Forster MJ, Sohal BH et al (2000) Reversible effects of long-term caloric restriction on protein oxidative damage. J Gerontol A Biol Sci Med Sci 55(11):B522–B529

    Article  PubMed  CAS  Google Scholar 

  • Hengemihle JM, Long JM et al (1999) Age-related psychomotor and spatial learning deficits in 129/SvJ mice. Neurobiology of Aging 20(1):9–18

    Article  PubMed  CAS  Google Scholar 

  • Hofman-Bang C, Rehnqvist N et al (1995) Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure. The Q10 Study Group. J Card Fail 1(2):101–107

    Article  PubMed  CAS  Google Scholar 

  • Hyson HC, Kieburtz K et al (2010) Safety and tolerability of high-dosage coenzyme Q10 in Huntington's disease and healthy subjects. Mov Disord 25(12):1924–1928

    Article  PubMed  Google Scholar 

  • Kagan VE, Tyurina YY et al (1998) Role of coenzyme Q and superoxide in vitamin E cycling. Subcell Biochem 30:491–507

    Article  PubMed  CAS  Google Scholar 

  • Kamsler A, Segal M (2003) Hydrogen peroxide modulation of synaptic plasticity. J Neurosci 23(1):269–276

    PubMed  CAS  Google Scholar 

  • Kamzalov S, Sumien N et al (2003) Coenzyme Q intake elevates the mitochondrial and tissue levels of Coenzyme Q and alpha-tocopherol in young mice. J Nutr 133(10):3175–3180

    PubMed  CAS  Google Scholar 

  • Kishida KT, Klann E (2007) Sources and targets of reactive oxygen species in synaptic plasticity and memory. Antioxid Redox Signal 9(2):233–244

    Article  PubMed  CAS  Google Scholar 

  • Koroshetz WJ, Jenkins BG et al (1997) Energy metabolism defects in Huntington's disease and effects of coenzyme Q10. Ann Neurol 41(2):160–165

    Article  PubMed  CAS  Google Scholar 

  • Lash LH, Sall JM (1993) Mitochondrial isolation from liver and kidney: strategy, techniques, and criteria for purity. In: Lash LH, Jones DP (eds) Methods in toxicology: mitochondrial dysfunction, vol. 2. Academic, San Diego, pp 8–12

    Google Scholar 

  • Lass A, Sohal RS (1998) Electron transport-linked ubiquinone-dependent recycling of alpha-tocopherol inhibits autooxidation of mitochondrial membranes. Arch Biochem Biophys 352(2):229–236

    Article  PubMed  CAS  Google Scholar 

  • Lass A, Forster MJ et al (1999a) Effects of coenzyme Q10 and alpha-tocopherol administration on their tissue levels in the mouse: elevation of mitochondrial alpha-tocopherol by coenzyme Q10. Free Radic Biol Med 26(11–12):1375–1382

    Article  PubMed  CAS  Google Scholar 

  • Lass A, Kwong LK, Sohal RS (1999b) Mitochondrial coenzyme Q content and aging. Biofactors 9:199–205

    Article  PubMed  CAS  Google Scholar 

  • Lee JM, Ross ER et al (1994) Spatial learning deficits in the aged rat: neuroanatomical and neurochemical correlates. Brain Res Bull 33(5):489–500

    Article  PubMed  CAS  Google Scholar 

  • Lenaz G, Fato R et al (1999) Localization and mobility of coenzyme Q in lipid bilayers and membranes. Biofactors 9:87–93

    Article  PubMed  CAS  Google Scholar 

  • Levine RL, Williams JA et al (1994) Carbonyl assays for determination of oxidatively modified proteins. Methods Enzymol 233:346–357

    Article  PubMed  CAS  Google Scholar 

  • Marcoff L, Thompson PD (2007) The role of coenzyme Q10 in statin-associated myopathy: a systematic review. J Am Coll Cardiol 49(23):2231–2237

    Article  PubMed  CAS  Google Scholar 

  • Matthews RT, Yang L et al (1998) "Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects." Proc Natl Acad Sci USA 95(15):8892–8897.

    Google Scholar 

  • McDonald SR, Sohal RS et al (2005) Concurrent administration of coenzyme Q10 and alpha-tocopherol improves learning in aged mice. Free Radic Biol Med 38(6):729–736

    Article  PubMed  CAS  Google Scholar 

  • McNamara RK, Skelton RW (1993) The neuropharmacological and neurochemical basis of place learning in the Morris water maze. Brain Res Brain Res Rev 18(1):33–49

    Article  PubMed  CAS  Google Scholar 

  • Miyoshi E, Wietzikoski E et al (2012) Both the doral hippocampus and the dorsolateral striatum are needed for rat navigation in the Morris water maze. Behav Brain Res 226(1):171–178

    Article  PubMed  Google Scholar 

  • Morisco C, Trimarco B et al (1993) Effect of coenzyme Q10 therapy in patients with congestive heart failure: a long-term multicenter randomized study. Clin Investig 71(8 Suppl):S134–S136

    PubMed  CAS  Google Scholar 

  • Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11(1):47–60

    Article  PubMed  CAS  Google Scholar 

  • Morrison JH, Hof PR (1997) Life and death of neurons in the aging brain. Science 278:412–419

    Article  PubMed  CAS  Google Scholar 

  • Mukai K, Kikuchi S et al (1990) Stopped-flow kinetic study of the regeneration reaction of tocopheroxyl radical by reduced ubiquinone-10 in solution. Biochim Biophys Acta 1035(1):77–82

    Article  PubMed  CAS  Google Scholar 

  • Nicolle MM, Gonzalez J et al (2001) Signatures of hippocampal oxidative stress in aged spatial learning-imparied rodents. Neuroscience 107:415–431

    Article  PubMed  CAS  Google Scholar 

  • Nohl H, Staniek K et al (2003) The biomolecule ubiquinone exerts a variety of biological functions. Biofactors 18:23–31

    Article  PubMed  CAS  Google Scholar 

  • Prosen CA, Dore DJ et al (2003) The functional age of hearing loss in a mouse model of presbycusis. I. Behavioral assessments. Hear Res 183(1–2):44–56

    Article  PubMed  Google Scholar 

  • Quiles JL, Ochoa JJ et al (2004) Coenzyme Q supplementation protects from age-related DNA double-strand breaks and increases lifespan in rats fed on a PUFA-rich diet. Exp Gerontol 39:189–194

    Article  PubMed  CAS  Google Scholar 

  • Reagan-Shaw S, Nihal M et al (2008) Dose translation from animal to human studies revisited. FASEB J 22(3):659–661

    Article  PubMed  CAS  Google Scholar 

  • Rosenfeldt F, Hilton D et al (2003) Systematic review of effect of coenzyme Q10 in physical exercise, hypertension and heart failure. Biofactors 18(1–4):91–100

    Article  PubMed  CAS  Google Scholar 

  • Rosenfeldt FL, Haas SJ et al (2007) Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Hum Hypertens 21(4):297–306

    PubMed  CAS  Google Scholar 

  • Serrano F, Klann E (2004) Reactive oxygen species and synaptic plasticity in the aging hippocampus. Ageing Res Rev 3(4):431–443

    Article  PubMed  CAS  Google Scholar 

  • Shukitt-Hale B, Carey A et al (2006) Effects of Concord grape juice on cognitive and motor deficits in aging. Nutrition 22(3):295–302

    Article  PubMed  CAS  Google Scholar 

  • Shults CW, Haas R (2005) Clinical trials of coenzyme Q10 in neurological disorders. Biofactors 25(1–4):117–126

    Article  PubMed  CAS  Google Scholar 

  • Sims NR (1993) Methods in toxicology: mitochondrial dysfunction. Academic, San Diego

    Google Scholar 

  • Sohal RS, Kamzalov S et al (2006) Effect of coenzyme Q10 intake on endogenous coenzyme Q content, mitochondrial electron transport chain, antioxidative defenses, and life span of mice. Free Radic Biol Med 40(3):480–487

    Article  PubMed  CAS  Google Scholar 

  • Someya S, Prolla TA (2010) Mitochondrial oxidative damage and apoptosis in age-related hearing loss. Mech Ageing Dev 131(7–8):480–486

    Article  PubMed  CAS  Google Scholar 

  • Someya S, Yamasoba T et al (2007) Genes encoding mitochondrial respiratory chain components are profoundly down-regulated with aging in the cochlea of DBA/2 J mice. Brain Res 1182:26–33

    Article  PubMed  CAS  Google Scholar 

  • Someya S, Tanokura M et al (2010) Effects of caloric restriction on age-related hearing loss in rodents and rhesus monkeys. Curr Aging Sci 3(1):20–25

    PubMed  Google Scholar 

  • Sumien N, Heinrich KR et al (2004) Short-term vitamin E intake fails to improve cognitive or psychomotor performance of aged mice. Free Radic Biol Med 36(11):1424–1433

    Article  PubMed  CAS  Google Scholar 

  • Sumien N, Sims MN et al (2006) Profiling psychomotor and cognitive aging in four-way cross mice. AGE 28:265–282

    Article  PubMed  Google Scholar 

  • Sumien N, Heinrich KR et al (2009) Prolonged intake of coenzyme Q10 impairs cognitive functions in mice. J Nutr 139(10):1926–1932

    Article  PubMed  CAS  Google Scholar 

  • Trounce I, Byrne E et al (1989) Decline in skeletal muscle mitochrondrial respiratory chain functions: possible factor in aging. Lancet 25:637–639

    Article  Google Scholar 

  • Turrens JF, Alexandre A et al (1985) Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria. Arch Biochem Biophys 237:408–414

    Article  PubMed  CAS  Google Scholar 

  • Turunen M, Olsson J et al (2004) Metabolism and function of coenzyme Q. Biochem Biophys Acta 1660:171–199

    Article  PubMed  CAS  Google Scholar 

  • Watson JB, Arnold MM et al (2006) Age-dependent modulation of hippocampal long-term potentiation by antioxidant enzymes. J Neurosci Res 84(7):1564–1574

    Article  PubMed  CAS  Google Scholar 

  • Willott JF, Kulig J et al (1984) The acoustic startle response in DBA/2 and C57BL/6 mice: relationship to auditory neuronal response properties and hearing impairment. Hear Res 16(2):161–167

    Article  PubMed  CAS  Google Scholar 

  • Winocur G, Moscovitch M (1990) Hippocampal and prefrontal cortex contributions to learning and memory: analysis of lesion and aging effects on maze learning in rats. Behav Neurosci 97:13–27

    Google Scholar 

Download references

Acknowledgments

This research was supported by the grants R01 AG27353 and AG22550 from the National Institutes of Health and the National Institute on Aging. The authors also wish to thank Tishcon Corp. (Westbury, NY) for providing with CoQ for this study.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Neuroscience and Institute for Aging and Alzheimer’s Disease Research, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie, Fort Worth, TX, 76107, USA

    Ritu A. Shetty, Michael J. Forster & Nathalie Sumien

Authors
  1. Ritu A. Shetty
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael J. Forster
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nathalie Sumien
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nathalie Sumien.

About this article

Cite this article

Shetty, R.A., Forster, M.J. & Sumien, N. Coenzyme Q10 supplementation reverses age-related impairments in spatial learning and lowers protein oxidation. AGE 35, 1821–1834 (2013). https://doi.org/10.1007/s11357-012-9484-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-012-9484-9

Keywords

Search

Navigation