Skip to main content
SpringerLink
Log in

Mitochondrial Ageing and the Beneficial Role of α-Lipoic Acid

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Oxidative damage has been implicated to be a major causative factor in the decline in physiological functions that occur during the ageing process. Mitochondria are known to be a rich source for the production of free radicals and, consequently, mitochondrial components are susceptible to lipid peroxidation (LPO) that decreases respiratory activity. In the present investigation, we have evaluated mitochondrial LPO, 8-oxo-dG, oxidized glutathione, reduced glutathione, ATP, lipoic acid, TCA cycle enzymes and electron transport chain (ETC) complex activities in the brain of young versus aged rats. In aged rats, the contents of LPO, oxidized glutathione and 8-oxo-dG were high whereas reduced glutathione, ATP, lipoic acid, TCA cycle enzymes and ETC complex activities were found to be low. Lipoic acid administration to aged rats reduced the levels of mitochondrial LPO, 8-oxo-dG and oxidized glutathione and enhanced reduced glutathione, ATP, lipoic acid and ETC complex activities. In young rats lipoic acid administration showed only minimal lowering the levels of LPO, 8-oxo-dG and oxidized glutathione and slight increase in the levels of reduced glutathione, ATP, lipoic acid, TCA cycle enzymes and ETC complex activities. These findings suggest that the dithiol, lipoic acid, provides protection against age-related oxidative damage in the mitochondria of aged rats.

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

Similar content being viewed by others

References

  1. Khaidakov M, Siegel ER, Shmookler Reis RJ (2006) Direct repeats in mitochondrial DNA and mammalian lifespan. Mech Ageing Dev 127:808–812

    Article  PubMed  CAS  Google Scholar 

  2. Olgun A, Akman S, Serdar MA, Kutluay T (2002) Oxidative phosphorylation enzyme complexes in caloric restriction. Exp Gerontol 37:639–645

    Article  PubMed  CAS  Google Scholar 

  3. Liu J, Atamna H, Kuratsune H, Ames BN (2002) Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Ann N Y Acad Sci 959:133–166

    Article  PubMed  CAS  Google Scholar 

  4. Hagen TM, Liu J, Lykkesfeldt J, Wehr CM, Ingersoll RT, Vinarsky V, Bartholomew JC, Ames BN (2002) Feeding acetyl-L-carnitine and lipoic acid to old rat significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci USA 99:1870–1875

    Article  PubMed  CAS  Google Scholar 

  5. Packer L, Kraemer K, Rimbach G (2001) Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutr 17:888–895

    Article  CAS  Google Scholar 

  6. Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, Cotman CW, Ames BN (2002) Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-α-lipoic acid. Proc Natl Acad Sci USA 99:2356–2361

    Article  PubMed  CAS  Google Scholar 

  7. Arivazhagan P, Ramanathan K, Panneerselvam C (2001) Effect of DL-α-lipoic acid on the status of lipid peroxidation and antioxidants in mitochondria of aged rats. J Nutr Biochem 12:1–6

    Article  Google Scholar 

  8. Lykkesfeldt J, Hagen TM, Vinarsky V, Ames BN (1998) Age-associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes – reversal with α-lipoic acid supplementation. FASEB J 12:1183–1189

    PubMed  CAS  Google Scholar 

  9. Sims NR (1993) Mitochondrial dysfunction. In: Lash LH, Jones DP (eds) Methods in toxicology. Academic Press, San Diego, 29–40

    Google Scholar 

  10. Ohkawa H, Ohishi N, Yaki K (1979) Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  PubMed  CAS  Google Scholar 

  11. Williamson JR, Corky BE (1969) Assays of intermediates of the citric acid cycle and related compounds by fluorometric enzymic methods. Methods Enzymol 13:434–513

    CAS  Google Scholar 

  12. Moron MS, Depierre JW, Mannervik B (1979) Levels of glutathione reductase and glutathione-S-transferase activities in rat lung and liver. Biochim Biophys Acta 582:67–70

    PubMed  CAS  Google Scholar 

  13. Griffith OW (1980) Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106:207–212

    Article  PubMed  CAS  Google Scholar 

  14. Latorre A, Barrio E, Moya A, Ayala FJ (1988) Mitochondrial DNA evolution in the Drosophila obscura group. Mol Biol Evol 5:717–728

    PubMed  CAS  Google Scholar 

  15. Hayakawa M, Torii K, Sugiyama S, Tanaka M, Ozawa T (1991) Age-associated accumulation of 8-hydroxydeoxyguanosine in mitochondrial DNA of human diaphragm. Biochem Biophys Res Commun 179:1023–1029

    Article  PubMed  CAS  Google Scholar 

  16. Nishida M (1961) Determination of thioctic acid. Chem Abstr 57: p 4965i

  17. King J (1965) The dehydrogenase or oxidoreductases-lactate dehydrogenase. In:Van D (ed) Practical clinical enzymology. Nostrand Company Limited, London, pp 83–93

  18. Reed LJ, Mukherjee BB (1969) α-KG dehydrogenase complex from Escherichia coli. Methods Enzymol 13:55–61

    Article  CAS  Google Scholar 

  19. Slater EC, Bonner WD (1952) The effect of fluoride on succinate oxidase system. Biochem J 52:185–196

    PubMed  CAS  Google Scholar 

  20. Ochoa S (1955) Malic dehydrogease from pig heart. In: Colowick SP, Kaplan NO (eds) Methods in enzymology. Academic Press, New York, pp 735–739

  21. Birch-Machin MA, Jackson S, Kler RS, Turnbull DM (1993) Mitochondrial dysfunction. In:Lash LH, Jones DP (eds) Methods in toxicology. Academic Press, San Diego, pp 51–59

    Google Scholar 

  22. Trounce IA, Kim YL, Jun AS, Wallace DC (1996) Assessment of mitochondrial oxidative phosphorylation in patients muscle biopsies, lymphoblasts, and transmitochondrial cell lines. Methods Enzymol 264:484–509

    PubMed  CAS  Google Scholar 

  23. Brich-Machin MA, Howell N, Turnbull DM (1993) Mitochondrial dysfunction. In: Lash LH, Jones DP (eds), Methods in toxicology. Academic Press, San Diego, pp 324–331

    Google Scholar 

  24. Berlett BS, Stadtman ER (1997) Protein oxidation in aging, disease and oxidative stress. J Biol Chem 272:20313–20316

    Article  PubMed  CAS  Google Scholar 

  25. Korotchkina LG, Yang HS, Tirosh O, Packer L, Patel MS (2001) Protection by thiols of the mitochondrial complexes from 4-hydroxy-2-nonenal. Free Rad Biol Med 30:992–999

    Article  PubMed  CAS  Google Scholar 

  26. Choi JH, Yu BP (1995) Brain synaptosomal ageing: free radicals and membrane fluidity. Free Rad Biol Med 18:33–139

    Article  Google Scholar 

  27. Fuchs J, Friesleben HJ, Mainka L, Zimmer G (1998) Mitochondrial sulphydrys groups under oligomycin inhibited, ageing and uncoupling conditions. Beneficial influence of cardioprotective drugs. Arch Biochem Biophys 266:83–88

    Article  Google Scholar 

  28. Hagan VE, Shvedova A, Serbinova S, Khan S, Swanson C, Powell R, Packer L (1992) Dihydrolipoic acid – a universal antioxidant both in the membrane and in the aqueous phase. Reduction of peroxyl, ascorbyl and chromanoxyl radicals. Biochem Pharmacol 44:1637–1649

    Article  Google Scholar 

  29. Tahara S, Mitsuyoshi M, Kaneko T (2001) Age-related changes in oxidative damage to lipids and DNA in rat skin. Mech Aging Devp 122:415–426

    Article  CAS  Google Scholar 

  30. Adelman R, Saul RL, Ames BN (1988) Oxidative damage to DNA: relation to species metabolic rate and life span. Proc Natl Acad Sci USA 85:2706–2708

    Article  PubMed  CAS  Google Scholar 

  31. Szabodos E, Fischer GM, Gallyas F, Kispal G Jr, Sumegi B (1999) Enhances ADP-ribosylation and its diminution by lipoate after ischemia-reperfusion in perfused rat heart. Free Rad Biol Med 27:1103–1113

    Article  Google Scholar 

  32. Devasagayam TPA, Subramanian M, Pradhan DS, Sies H (1993) Prevention of singlet oxygen induced DNA damage by lipoate. Chem Boil Interact 86:79–92

    Article  CAS  Google Scholar 

  33. Fannin SW, Lesnefsky EJ, Slabe TJ, Hassan MO, Hoppel CL (1999) Aging selectively decreases oxidative capacity in rat heart interfibrillary mitochondria. Arch Biochem Biophys 372:399–407

    Article  PubMed  CAS  Google Scholar 

  34. Arivazhagan P, Ramanathan K, Panneerselvam C (2001) Effect of DL-α-lipoic acid on mitochondrial enzymes in aged rats. Chem Biol Interact 138:189–198

    Article  PubMed  CAS  Google Scholar 

  35. Muller-Hocker J, Schafer S, Link TA, Possekel S, Hammer C (1996) Defects of the respiratory chain in various tissues of old monkeys: a cytochemical-immunocytochemical study. Mech Aging Devp 86:197–213

    Article  CAS  Google Scholar 

  36. Hoch FL (1992) Cardiolipins and biomembrane function. Biochim Biophys Acta 1113:71–133

    PubMed  CAS  Google Scholar 

  37. Paradies G, Petrosillo G, Pistolese M, Ruggiero FM (2000) The effect of reactive oxygen species generated from the mitochondrial electron transport chain on the cytochrome c oxidase activity and on the cardiolipin content in bovine heart submitochondrial particles. FEBS Lett 466:323–326

    Article  PubMed  CAS  Google Scholar 

  38. Fernandez-Checa JC, Yi J, GarciaRuiz C, Okhtens M, Kaplowitz N (1996) Plasma membrane and mitochondrial transport of hepatic reduced glutathione. Semi Liver Dis 16:147–158

    Article  CAS  Google Scholar 

  39. Garcia-Ruiz C, Collel A, Morales A (1995) Role of oxidative stress generated from the mitochondrial transport chain and glutathione status in loss of mitochondrial function and activation of transcription factor, NF-kB. Studies with isolated mitochondria and rat hepatocytes. Mol Pharmacol 48:825–834

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Yokohama City University, Maioka-cho 641-12, Totsuka Ku, Yokohama, 244-0813, Japan

    A. R. Palaniappan & A. Dai

Authors
  1. A. R. Palaniappan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Dai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Palaniappan, A.R., Dai, A. Mitochondrial Ageing and the Beneficial Role of α-Lipoic Acid. Neurochem Res 32, 1552–1558 (2007). https://doi.org/10.1007/s11064-007-9355-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-007-9355-4

Keywords

Search

Navigation