Skip to main content
SpringerLink
Log in

Mitochondrial alterations, cellular response to oxidative stress and defective degradation of proteins in aging

  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

Respiratory function decline and increase ofoxidative stress in mitochondria have beenproposed as important contributors to humanaging. A wide spectrum of alterations in agedindividuals and senescent cells are similar andare correlated to cellular response tosublethal dose of oxidative stress. Thesealterations and responses include: (1) declinein mitochondrial respiratory function; (2)increase in the rate of production of reactiveoxygen species (ROS); (3) accumulation ofmitochondrial DNA (mtDNA) mutations; (4)increase in the levels of oxidative damage toDNA, protein, and lipids; and (5) decrease inthe capacities of degradation of oxidativelydamaged proteins and other macromolecules. Responses to oxidative stress and theirsubsequent interactions in tissues result inthe deleterious effect of ROS on the cellularfunction, which culminate in aging anddegenerative diseases. In this review, wefocus on the roles that ROS play in age-relatedoxidative damage to mtDNA and proteins andoxidative stress responses at the molecular andcellular levels. The alterations of geneexpression profiles elicited by oxidativestress in aging animals are discussed. Wesuggest that the increase in mitochondrialproduction of ROS and decline in the cellularcapacity to cope with oxidative stress andsubsequent accumulation of mtDNA mutations andoxidized proteins play an important role in theaging process.

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.

Similar content being viewed by others

References

  • Agarwal S and Sohal RS (1994a) Aging and protein oxidative damage. Mech Ageing Dev 75: 11-19

    PubMed  Google Scholar 

  • Agarwal S and Sohal RS (1994b) Aging and proteolysis of oxidized proteins. Arch Biochem Biophys 309: 24-28

    PubMed  Google Scholar 

  • Agarwal S and Sohal RS (1995) Differential oxidative damage to mitochondrial proteins during aging. Mech Ageing Dev 85: 55-63

    PubMed  Google Scholar 

  • Ames BN, Shigenaga MK and Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 90: 7915-7922

    Google Scholar 

  • Ames BN, Shigenaga MK and Hagen TM (1995) Mitochondrial decay in aging. Biochim Biophys Acta 1271: 165-170

    PubMed  Google Scholar 

  • Aspnes LE, Lee CM, Weindruch R, Chung SS, Roecker EB and Aiken JM (1997) Caloric restriction reduces fiber loss and mitochondrial abnormalities in aged rat muscle. FASEB J 11: 573-581

    PubMed  Google Scholar 

  • Barrientos A, Casademont J, Cardellach F, Ardite E, Estivill X, Urbano-Marquez A, Fernandez-Checa JC and Nunes V (1997a) Qualitative and quantitative changes in skeletal muscle mtDNA and expression of mitochondrial-encoded genes in the human aging process. Biochem Mol Med 62: 165-171

    PubMed  Google Scholar 

  • Barrientos A, Casademont J, Cardellach F, Estivill X, Urbano-Marquez A and Nunes V (1997b) Reduced steady-state levels of mitochondrial RNA and increased mitochondrial DNA amount in human brain with aging. Mol Brain Res 52: 284-289

    PubMed  Google Scholar 

  • Beckman KB and Ames BN (1998) The free radical theory of aging matures. Physiol Rev 78: 547-581

    PubMed  Google Scholar 

  • Bednarski E, Ribak CE and Lynch G (1997) Suppression of cathepsins B and L causes a proliferation of lysosomes and the formation of meganeurites in hippocampus. J Neurosci 17: 4006-4021

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Bernardi P, Petronilli V, Di Lisa F and Forte M (2001) A mitochondrial perspective on cell death. Trends Biochem Sci 26: 112-117

    PubMed  Google Scholar 

  • Bladier C, Wolvetang EJ, Hutchinson P, de Haan JB and Kola I (1997) Response of a primary human fibroblast cell line to H2O2: senescence-like growth arrest or apoptosis. Cell Growth Different 8: 589-598

    Google Scholar 

  • Brambilla L, Gaetano C, Sestili P, O'Donnel V, Azzi A and Cantoni O (1997) Mitochondrial respiratory chain deficiency leads to overexpression of antioxidant enzymes. FEBS Lett 418: 247-250

    PubMed  Google Scholar 

  • Brown GC (1992) Control of respiration and ATP synthesis in mammalian mitochondria and cells. Biochem J 284: 1-13

    PubMed  Google Scholar 

  • Brunk UT, Zhang H, Dalen H and Ollinger K (1995) Exposure of cells to nonlethal concentrations of hydrogen peroxide induces degeneration-repair mechanisms involving lysosomal destabilization. Free Radic Biol Med 19: 813-822

    PubMed  Google Scholar 

  • Calleja M, Pena P, Ugalde C, Ferreiro C, Marco R and Garesse R (1993) Mitochondrial DNA remains intact during Drosophila aging, but the levels of mitochondrial transcripts are significantly reduced. J Biol Chem 268: 18891-18897

    PubMed  Google Scholar 

  • Chance B, Sies H and Boveris H (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59: 527-605

    PubMed  Google Scholar 

  • Chen Q and Ames BN (1994) Senescence-like growth arrest induced by hydrogen peroxide in human diploid fibroblast F56 cells. Proc Natl Acad Sci USA 91: 4130-4134

    PubMed  Google Scholar 

  • Clayton DA (1982) Replication of animal mitochondrial DNA. Cell 28: 693-705

    Article  PubMed  Google Scholar 

  • Cuervo AM and Dice JF (2000a) When lysosomes get old. Exp Gerontol 35: 119-131

    PubMed  Google Scholar 

  • Cuervo AM and Dice JF (2000b) Age-related decline in chaperonemediated autophagy. J Biol Chem 275: 31505-31513

    PubMed  Google Scholar 

  • de Grey ADNJ (1997) A proposed refinement of the mitochondrial free radical theory of aging. BioEssays 19: 161-166

    PubMed  Google Scholar 

  • Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, Peacocke M and Campisi J (1995) A biomarker that identifies senescent cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 92: 9363-9367

    PubMed  Google Scholar 

  • Dubey A, Forster MJ, Lal H and Sohal RS (1996) Effect of age and caloric intake on protein oxidation in different brain regions and on behavioral functions of the mouse. Arch Biochem Biophys 333: 189-197

    PubMed  Google Scholar 

  • Dumont P, Burton M, Chen QM, Gonos ES, Frippiat C, Mazarati JB, Eliaers F, Remacle J and Toussaint O (2000) Induction of replicative senescence biomarkers by sublethal oxidative stresses in normal human fibroblast. Free Radic Biol Med 28: 361-373

    PubMed  Google Scholar 

  • Elliott RM, Southon S and Archer DB (1999) Oxidative insult specifically decreases levels of a mitochondrial transcript. Free Radic Biol Med 26: 646-655

    PubMed  Google Scholar 

  • Esposito LA, Melov S, Panov A, Cottrell BA and Wallace DC (1999) Mitochondrial disease in mouse results in increased oxidative stress. Proc Natl Acad Sci USA 96: 4820-4825

    PubMed  Google Scholar 

  • Fahn HJ, Wang LS, Kao SH, Chang SC, Huang MH and Wei YH (1998) Smoking-associated mitochondrial DNA mutations and lipid peroxidation in human lung tissues. Am J Respir Cell Mol Biol 19: 901-909

    PubMed  Google Scholar 

  • Fernandez-Silva SP, Petruzzela V, Fracasso F, Gadaleta MN and Cantatore P (1992) Reduced synthesis of mtRNA in isolated mitochondria of senescent rat brain. Biochem Biophys Res Commun 176: 645-653

    Google Scholar 

  • Frippiat C, Chen QM, Zdano S, Magalhaes JP, Remacle J and Toussaint O (2001) Subcytotoxic H2O2 stress triggers a release of transforming growth factor-b1, which induces biomarkers of cellular senescence of human diploid fibroblasts. J Biol Chem 276: 2531-2537

    PubMed  Google Scholar 

  • Fu GK and Markovitz DM (1998) The human LON protease binds to mitochondrial promoters in a single-stranded, site-specific, strand-specific manner. Biochemistry 37: 1905-1909

    PubMed  Google Scholar 

  • Gadaleta MN, Petruzzella V, Renis M, Fracasso F and Cantatore P (1990) Reduced transcription of mitochondrial DNA in the senescent rat. Tissue dependence and effect of L-carnitine. Eur J Biochem 187: 501-506

    PubMed  Google Scholar 

  • Gadaleta MN, Rainaldi G, Lezza AMS, Milella F, Fracasso F and Cantatore P (1992) Mitochondrial DNA copy number and mitochondrial DNA deletion in adult and senescent rats. Mutat Res 275: 181-193

    PubMed  Google Scholar 

  • Garcia-Ruiz C, Colell A, Morales A, Kaplowitz N and Fernandez-Checa JC (1995) Role of oxidative stress generated from the mitochondrial electron transport chain and mitochondrial glutathione status in loss of mitochondrial function and activation of transcription factor nuclear factor-kB: studies with isolated mitochondria and rat hepatocytes. Mol Pharmacol 48: 825-834

    PubMed  Google Scholar 

  • Gardner PR, Nguyen DD and White CW (1994) Aconitase is a sensitive and critical target of oxygen poisoning in cultured mammalian cells and in rat lungs. Proc Natl Acad Sci USA 91: 12248-12252

    PubMed  Google Scholar 

  • Gonos ES, Derventzy A, Kveiborg M, Agiostratidou G, Kassem M, Clark BFC, Jat PS and Rattan SIS (1998) Cloning and identification of genes that associate with mammalian replicative senescence. Exp Cell Res 240: 66-74

    PubMed  Google Scholar 

  • Grune T (2000) Oxidative stress, aging and the proteasomal system. Biogerontology 1: 31-40

    PubMed  Google Scholar 

  • Grune T, Reinheckel T and Davies KJA (1997) Degradation of oxidized proteins in mammalian cells. FASEB J 11: 526-534

    PubMed  Google Scholar 

  • Harman D (1956) A theory based on free radical and radiation chemistry. J Gerontol 11: 298-300

    PubMed  Google Scholar 

  • Harman D (1972) The biological clock: the mitochondria. J Am Geriatr Soc 20: 145-147

    PubMed  Google Scholar 

  • Harman D (1983) Free radical theory of aging: Consequences of mitochondrial aging. Age 6: 86-94

    Google Scholar 

  • Hayakawa M, Hattori K, Sugiyama S and Ozawa T (1992) Ageassociated oxygen damage and mutations in mitochondrial DNA in human heart. Biochem Biophys Res Commun 189: 979-985

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Higami Y and Shimokawa I (2000) Apoptosis in the aging process. Cell Tissue Res 301: 125-132

    PubMed  Google Scholar 

  • Hruszkewycz AM (1992) Lipid peroxidation and mtDNA degeneration. A hypothesis. Mutat Res 275: 243-248

    Google Scholar 

  • Hsieh RH, Hou JH, Hsu HS and Wei YH (1994) Age-dependent respiratory function decline and DNA deletions in human muscle mitochondria. Biochem Mol Biol Int 32: 1009-1022

    PubMed  Google Scholar 

  • Johnson FB, Sinclair DA and Guarente L (1999) Molecular biology of aging. Cell 96: 291-302

    PubMed  Google Scholar 

  • Kokoszka JE, Coskun P, Esposito LA and Wallace DC (2001) Increased mitochondrial oxidative stress in the Sod2 (+/-) mouse results in the age-related decline of mitochondrial function culminating in increased apoptosis. Proc Natl Acad Sci USA 98: 2278-2283

    PubMed  Google Scholar 

  • Kovalenko SA, Kopsidas G, Islam MM, Heffernan D, Fitzpatrick J, Caragounis A, Gingold E and Linnane AW (1998) The ageassociated decrease in the amount of amplifiable full-length mitochondrial DNA in human skeletal muscle. Biochem Mol Biol Int 46: 1233-1241

    PubMed  Google Scholar 

  • Kowald A (1999) The mitochondrial theory of aging: Do damaged mitochondria accumulate by delayed degeneration? Exp Gerontol 34: 605-612

    PubMed  Google Scholar 

  • Kroemer G, Dallaporta B and Resche-Rigon M (1998) The mitochondrial death/life regulator in apoptosis and necrosis. Annu Rev Physiol 60: 619-642

    PubMed  Google Scholar 

  • Kurz DJ, Decary S, Hong Y and Erusalimsky JD (2000) Senescence-associated b-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J Cell Sci 113: 3613-3622

    PubMed  Google Scholar 

  • Lander HM (1997) An essential role for free radicals and derived species in signal transduction. FASEB J 11: 118-124

    PubMed  Google Scholar 

  • Lass A, Sohal BH, Weindruch R, Forster MJ and Sohal RS (1998) Caloric restriction prevents age-associated accrual of oxidative damage to mouse skeletal muscle mitochondria. Free Radic Biol Med 25: 1089-1097

    PubMed  Google Scholar 

  • Lee CK, Klopp RG, Weindruch R and Prolla TA (1999a) Gene expression profile of aging and its retardation by caloric restriction. Science 285: 1390-1393

    PubMed  Google Scholar 

  • Lee CK, Weindruch R and Prolla TA (2000a) Gene-expression profile of the ageing brain in mice. Nat Genet 25: 294-297

    PubMed  Google Scholar 

  • Lee HC and Wei YH (1997a) Mutation and oxidative damage of mitochondrial DNA and defective turnover of mitochondria in human aging. J Formos Med Assoc 96: 770-778

    PubMed  Google Scholar 

  • Lee HC and Wei YH (1997b) The role of mitochondria in human aging. J Biomed Sci 4: 319-326

    PubMed  Google Scholar 

  • Lee HC and Wei YH (2000) Mitochondrial role in life and death of the cell. J Biomed Sci 7: 2-15

    PubMed  Google Scholar 

  • Lee HC, Lim ML, Lu CY, Liu VW, Fahn HJ, Zhang C, Nagley P and Wei YH (1999b) Concurrent increase of oxidative DNA damage and lipid peroxidation together with mitochondrial DNA mutation in human lung tissues during aging-smoking enhances oxidative stress on the aged tissues. Arch Biochem Biophys 362: 309-316

    PubMed  Google Scholar 

  • Lee HC, Lu CY, Fahn HJ and Wei YH (1998) Aging-and smokingassociated alteration in the relative content of mitochondrial DNA in human lung. FEBS Lett 441: 292-296

    PubMed  Google Scholar 

  • Lee HC, Pang CY, Hsu HS and Wei YH (1994a) Differential accumulations of 4,977 bp deletion in mitochondrial DNA of various tissues in human ageing. Biochim Biophys Acta 1226: 37-43

    PubMed  Google Scholar 

  • Lee HC, Pang CY, Hsu HS and Wei YH (1994b) Ageing-associated tandem duplications in the D-loop of mitochondrial DNA of human muscle. FEBS Lett 354: 79-83

    PubMed  Google Scholar 

  • Lee HC, Yin PH, Yu TN, Chang YD, Hsu WC, Kao SY, Chi CW, Liu TY and Wei YH (2000b) Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells. Biochem J 348: 425-432

    PubMed  Google Scholar 

  • Lee HC, Yin PH, Yu TN, Chang YD, Hsu WC, Kao SY, Chi CW, Liu TY and Wei YH (2001) Accumulation of mitochondrial DNA deletions in human oral tissues-Effects of betel quid chewing and oral cancer. Mutat Res 493: 67-74

    PubMed  Google Scholar 

  • Lightowlers RN, Jacobs HT, Kajander OA (1999) Mitochondrial DNA-all things bad? Trends Genet 15: 91-93

    PubMed  Google Scholar 

  • Lopez-Huertas E, Charlton WL, Johnson B, Graham IA and Baker A (2000) Stress induces peroxisome biogenesis genes. EMBO J 19: 6770-6777

    PubMed  Google Scholar 

  • Lu CY, Lee HC, Fahn HJ and Wei YH (1999) Oxidative damage elicited by imbalance of free radical scavenging enzymes is associated with large-scale mtDNA deletions in aging human skin. Mutat Res 423: 11-21

    PubMed  Google Scholar 

  • Luciakova K, Sokolikova B, Chloupkova M and Nelson BD (1999) Enhanced mitochondrial biogenesis is associated with increased expression of the mitochondrial ATP-dependent Lon protease. FEBS Lett 444: 186-188

    PubMed  Google Scholar 

  • Masoro EJ (2000) Caloric restriction and aging: an update. Exp Gerontol 35: 299-305

    PubMed  Google Scholar 

  • Melov S, Coskun P, Patel M, Tuinstra R, Cottrell B, Jun AS, Zastawny TH, Dizdaroglu M, Goodman SI, Huang TT, Miziorko H, Epstein CJ and Wallace DC (1999) Mitochondrial disease in superoxide dismutase 2 mutant mice. Proc Natl Acad Sci USA 96: 846-851

    PubMed  Google Scholar 

  • Melov S, Ravenscroft J, Malik S, Gill MS, Walker DW, Clayton PE, Wallace DC, Malfroy B, Doctrow SR and Lithgow GJ (2000) Extension of life-span with superoxide dismutase/catalase mimetics. Science 289: 1567-1569

    PubMed  Google Scholar 

  • Michikawa Y, Mazzucchelli F, Bresolin N, Scarlato G and Attardi G (1999) Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication. Science 286: 774-779

    PubMed  Google Scholar 

  • Morel F, Mazet F, Touraille S and Alziari S (1995) Changes in the respiratory chain complexes activities and in the mitochondrial DNA content during ageing in D. subobscura. Mech Ageing Dev 84: 171-181

    PubMed  Google Scholar 

  • Müller-Höcker J (1989) Cytochrome-c-oxidase deficient cardiomyocytes in the human heart-an age-related phenomenon. A histochemical ultracytochemical study. Am J Pathol 134: 1167-1173

    PubMed  Google Scholar 

  • Müller-Höcker J (1990) Cytochrome c oxidase deficient fibers in the limb muscle and diphragm of man without muscular disease: an age-related alteration. J Neurol Sci 100: 14-21

    PubMed  Google Scholar 

  • Nakano M, Onzil F, Mizuno T and Gotoh (1995) Age-related changes in the lipofuscin accumulation of brain and heart. Gerontology 41: 69-80

    Google Scholar 

  • Oliver CN, Ahn BW, Moerman EJ, Goldstein S and Stadtman ER (1987) Age-related changes in oxidized proteins. J Biol Chem 262: 5488-5491

    PubMed  Google Scholar 

  • Ozawa T (1997) Genetic and functional changes in mitochondria associated with aging. Physiol Rev 77: 425-464

    PubMed  Google Scholar 

  • Pang CY, Lee HC, Yang JH and Wei YH (1994) Human skin mitochondrial DNA deletions associated with light exposure. Arch Biochem Biophys 312: 534-538

    PubMed  Google Scholar 

  • Papa S (1996) Mitochondrial oxidative phosphorylation changes in the life span. Molecular aspects and physiopathological implications. Biochim Biophys Acta 1276: 87-105

    PubMed  Google Scholar 

  • Poyton RO and McEwen JE (1996) Crosstalk between nuclear and mitochondrial genomes. Annu Rev Biochem 65: 563-607

    PubMed  Google Scholar 

  • Richter C, Gogvadze V, Laffranchi R, Schlapbach R, Schnizer M, Suter M, Walter P and Yaffee M (1995) Oxidants in mitochondria: from physiology to disease. Biochim Biophys Acta 1271: 67-74

    PubMed  Google Scholar 

  • Scarpulla RC (1997) Nuclear control of respiratory chain expression in mammalian cells. J Bioenerg Biomembr 29: 109-119

    PubMed  Google Scholar 

  • Shigenaga MK, Hagen TM and Ames BN (1994) Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA 91: 10771-10778

    PubMed  Google Scholar 

  • Sitte N, Huber M, Grune T, Ladhoff A, Doecke WD, von Zglinicki T and Davies KJA (2000a) Proteasome inhibition by lipofuscin/ ceroid during postmitotic aging of fibroblasts. FASEB J 14: 1490-1498

    PubMed  Google Scholar 

  • Sitte N, Merker K and Grune T (1998) Proteasome-dependent degradation of oxidized proteins in MRC-5 fibroblasts. FEBS Lett 440: 399-402

    PubMed  Google Scholar 

  • Sitte N, Merker K, von Zglinicki T, Grune T and Davies KJA (2000b) Protein oxidation and degradation during cellular senescence of human BJ fibroblasts: part I-effects of proliferative senescence. FASEB J 14: 2495-2502

    PubMed  Google Scholar 

  • Sitte N, Merker K, von Zglinicki T, Davies KJA and Grune T (2000c) Protein oxidation and degradation during cellular senescence of human BJ fibroblasts: part II-aging of nondividing cells. FASEB J 14: 2503-2510

    PubMed  Google Scholar 

  • Smith CD, Carney JM, Starke-Reed PE, Oliver CN, Stadtman ER, Floyd RA and Markesbery WR (1991) Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc Natl Acad Sci USA 88: 10540-10543

    PubMed  Google Scholar 

  • Sohal RS, Agarwal S, Candas M, Forster MJ and Lal H (1994a) Effect of age and caloric restriction on DNA oxidative damage in different tissues of C57BL/6 mice. Mech Ageing Dev 76: 215-224

    PubMed  Google Scholar 

  • Sohal RS, Ku HH, Agarwal S, Forster MJ and Lal H (1994b) Oxidative damage, mitochondrial oxidant generation, and antioxidant defenses during aging and in response to food restriction in the mouse. Mech Ageing Dev 74: 121-133

    PubMed  Google Scholar 

  • Sohal RS, Sohal BH and Orr WC (1995) Mitochondrial superoxide and hydrogen peroxide generation, protein oxidative damage and longevity in different species of flies. Free Radic Biol Med 19: 499-504

    PubMed  Google Scholar 

  • Sugiyama S, Takasawa M, Hayakawa M and Ozawa T (1993) Changes in skeletal muscle, heart and liver mitochondrial electron transport activities in rats and dogs of various ages. Biochem Mol Biol Int 30: 937-944

    PubMed  Google Scholar 

  • Takasawa M, Hayakawa M, Sugiyama S, Hattori K, Ito T and Ozawa T (1993) Age-associated damage in mitochondrial function in rat heart. Exp Gerontol 28: 269-280

    PubMed  Google Scholar 

  • Terman A and Brunk UT (1998) Ceroid/lipofuscin formation in cultured human fibroblasts: the role of oxidative stress and lysosomal proteolysis. Mech Ageing Dev 104: 277-291

    PubMed  Google Scholar 

  • Terman A, Abrahamsson N and Brunk UT (1999a) Ceroid/ lipofuscin-loaded human fibroblasts show increased susceptibility to oxidative stress. Exp Gerontol 34: 755-770

    PubMed  Google Scholar 

  • Terman A, Dalen H and Brunk UT (1999b) Ceroid/lipofuscinloaded human fibroblasts show decreased survival time and diminished autophagocytosis during amino acid starvation. Exp Gerontol 34: 943-957

    PubMed  Google Scholar 

  • Torii K, Sugiyama S, Takagi K, Satake T and Ozawa T (1992) Agerelated decrease in respiratory muscle mitochondrial function in rats. Am J Respir Cell Mol Biol 6: 88-92

    PubMed  Google Scholar 

  • Trounce I, Byrne E and Marzuki S (1989) Decline in skeletal muscle mitochondrial respiratory chain function: possible factor in ageing. Lancet i: 637-639

    Google Scholar 

  • Wallace DC (1992) Diseases of the mitochondrial DNA. Annu Rev Biochem 61: 1175-1212

    PubMed  Google Scholar 

  • Wang Y, Michikawa Y, Mallidis C, Bai Y, Woodhouse L, Yarasheski KE, Miller CA, Askanas V, Engel WK, Bhasin S and Attardi G (2001) Muscle-specific mutations accumulate with aging in critical human mtDNA control sites for replication. Proc Natl Acad Sci USA 98: 4022-4027

    PubMed  Google Scholar 

  • Waterlow JC (1984) Protein turnover with special reference to man. Q J Exp Physiol 69: 409-438

    PubMed  Google Scholar 

  • Wei YH (1992) Mitochondrial DNA alterations as aging-associated molecular events. Mutat Res 275: 145-155

    PubMed  Google Scholar 

  • Wei YH (1998) Oxidative stress and mitochondrial DNA mutations in human aging. Proc Soc Exp Biol Med 217: 53-63

    PubMed  Google Scholar 

  • Wei YH, Kao SH and Lee HC (1996a) Simultaneous increase of mitochondrial DNA deletions and lipid peroxidation in human aging. Ann N Y Acad Sci 786: 24-43

    PubMed  Google Scholar 

  • Wei YH, Lee HC, Pang CY, Lu CY and Ma YS (1998) Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of mitochondrial respiratory function. Ann N Y Acad Sci 854: 155-170

    PubMed  Google Scholar 

  • Wei YH, Lu CY, Wei CY, Ma YS and Lee HC (2001) Oxidative stress in human aging and mitochondrial disease-consequences 244 of defective mitochondrial respiration and impaired antioxidant enzyme system. Chinese J Physiol 44: 1-11

    Google Scholar 

  • Wei YH, Pang CY, You BJ and Lee HC (1996b) Tandem duplications and large-scale deletions of mitochondrial DNA are early molecular events of human aging process. Ann N Y Acad Sci 786: 82-101

    PubMed  Google Scholar 

  • Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell, Scarpulla RC and Spiegelman BM (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98: 115-124

    PubMed  Google Scholar 

  • Yakes FM and van Houten B (1997) Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci USA 94: 514-519

    Google Scholar 

  • Yan LJ, Levine RL and Sohol RS (1997) Oxidative damage during aging targets mitochondrial aconitase. Proc Natl Acad Sci USA 94: 11168-11172

    PubMed  Google Scholar 

  • Yan LJ and Sohal RS (1998) Mitochondrial adenine nucleotide translocase is modified oxidatively during aging. Proc Natl Acad Sci USA 95: 12896-12901

    PubMed  Google Scholar 

  • Yang JH, Lee HC and Wei YH (1995) Photoageing-associated mitochondrial DNA length mutations in human skin. Arch Dermatol Res 287: 641-648

    PubMed  Google Scholar 

  • Yen TC, Chen SH, King KL and Wei YH (1989) Liver mitochondrial respiratory functions decline with age. Biochem Biophys Res Commun 65: 994-1003

    Google Scholar 

  • Yen TC, King KL, Lee HC, Yeh SH and Wei YH (1994) Agedependent increase of mitochondrial DNA deletions together with lipid peroxides and superoxide dismutase in human liver mitochondria. Free Radic Biol Med 16: 207-214

    PubMed  Google Scholar 

  • Zou S, Meadows S, Sharp L, Jan LY and Jan YN (2000) Genomewide study of aging and oxidative stress response in Drosophila melanogaster. Proc Natl Acad Sci USA 97: 13726-13731

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, National Yang-Ming University, Taipei, Taiwan, 112, Republic of China

    Hsin-Chen Lee & Yau-Huei Wei

Authors
  1. Hsin-Chen Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yau-Huei Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, HC., Wei, YH. Mitochondrial alterations, cellular response to oxidative stress and defective degradation of proteins in aging. Biogerontology 2, 231–244 (2001). https://doi.org/10.1023/A:1013270512172

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1013270512172

Search

Navigation