Synthesis, Modification and Turnover of Proteins during Aging

  • Suresh I. S. Rattan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 694)


Alterations in the rate and extent of protein synthesis, accuracy, post-translational modifications and turnover are among the main molecular characteristics of aging. A decline in the cellular capacity through proteasomal and lysosomal pathways to recognize and preferentially degrade damaged proteins leads to the accumulation of abnormal proteins during aging. The consequent increase in molecular heterogeneity and impaired functioning of proteins is the basis of several age-related pathologies, such as cataracts, sarcopenia and neurodegerative diseases. Understanding the proteomic spectrum and its functional implications during aging can facilitate developing effective means of intervention, prevention and therapy of aging and age-related diseases.


Human Lens Ation Factor Protein Error Protein Synthetic Machinery Proteomic Spectrum 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Rattan SIS. Synthesis, modifications and turnover of proteins during aging. Exp Gerontol 1996; 31:33–47.PubMedCrossRefGoogle Scholar
  2. 2.
    Rattan SIS. Transcriptional and translational dysregulation during aging. In: von Zglinicki T, ed. Aging at the Molecular Level. Dordrecht: Kluwer Acad Publ, 2003:179–91.Google Scholar
  3. 3.
    Abbott CM, Proud CG. Translational factors: in sickness and in health. Trends Biochem Sci 2004; 29:25–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Holliday R. The current status of the protein error theory of aging. Exp Gerontol 1996; 31:449–52.PubMedCrossRefGoogle Scholar
  5. 5.
    Hipkiss A. Accumulation of altered proteins and ageing: causes and effects. Exp Gerontol 2006; 41:464–73.PubMedCrossRefGoogle Scholar
  6. 6.
    Rattan SIS. Translation and post-translational modifications during aging. In: Macieira-Coelho A, ed. Molecular Basis of Aging. Boca Raton, Florida: CRC Press, 1995:389–420.Google Scholar
  7. 7.
    Luce MC, Bunn CL. Altered sensitivity of protein synthesis to paromomycin in extracts from aging human diploid fibroblasts. Exp Gerontol 1987; 22:165–77.PubMedCrossRefGoogle Scholar
  8. 8.
    Luce MC, Bunn CL. Decreased accuracy of protein synthesis in extracts from aging human diploid fibroblasts. Exp Gerontol 1989; 24:113–25.PubMedCrossRefGoogle Scholar
  9. 9.
    Holliday R, Rattan SIS. Evidence that paromomycin induces premature ageing in human fibroblasts. Monogr Devl Biol 1984; 17:221–33.Google Scholar
  10. 10.
    Buchanan JH, Stevens A, Sidhu J. Aminoglycoside antibiotic treatment of human fibroblasts: intracellular accumulation, molecular changes and the loss of ribosomal accuracy. Eur J Cell Biol 1987; 43:141–7.PubMedGoogle Scholar
  11. 11.
    Nyström T. Translational fidelity, protein oxidation and senescence: lessons from bacteria. Ageing Res Rev 2002; 1:693–703.PubMedCrossRefGoogle Scholar
  12. 12.
    Nyström T. Aging in bacteria. Curr Opin Microbiol 2002; 5:596–601.PubMedCrossRefGoogle Scholar
  13. 13.
    Silar P, Rossignol M, Haedens V et al. Deletion and dosage modulation of the eEF1A gene in Podospora anserina: effect on the life cycle. Biogerontology 2000; 1:47–54.PubMedCrossRefGoogle Scholar
  14. 14.
    Holbrook MA, Menninger JR. Erythromycin slows aging of Saccharomyces cerevisiae. J Gerontol Biol Sci 2002; 57A:B29–B36.Google Scholar
  15. 15.
    Dever TE. Translation initiation: adept at adapting. TIBS 1999; 24:398–403.PubMedGoogle Scholar
  16. 16.
    Hershey JWB, Merrick WC. The pathway and mechanism of inititation of protein synthesis. In: Sonenberg N, Hershey JWB, Mathews MB, eds. Translational Control of Gene Expression. New York: Cold Spring Harbor Laboratory Press, 2000:33–88.Google Scholar
  17. 17.
    Chen ZP, Chen KY. Dramatic attenuation of hypusine formation on eukaryotic initiation factor 5A during senescence of IMR-90 human diploid fibroblasts. J Cell Physiol 1997; 170:248–54.PubMedCrossRefGoogle Scholar
  18. 18.
    Saini P, Eyler DE, Green R et al. Hypusine-containing protein eIF5A promotes translation elongation. Nature 2009; 459:118–21.PubMedCrossRefGoogle Scholar
  19. 19.
    Ward W, Richardson A. Effect of age on liver protein synthesis and degradation. Hepatol 1991; 14:935–48.CrossRefGoogle Scholar
  20. 20.
    Van Remmen H, Ward WF, Sabia RV et al. Gene expression and protein degradation. In: Masoro E, editor. Handbook of Physiology: Aging. Oxford University Press, 1995:171–234.Google Scholar
  21. 21.
    Riis B, Rattan SIS, Clark BFC et al. Eukaryotic protein elongation factors. TIBS 1990; 15:420–4.PubMedGoogle Scholar
  22. 22.
    Andersen GR, Nissen P, Nyborg J. Elongation factors in protein biosynthesis. Trends Biochem Sci 2003; 28:434–41.PubMedCrossRefGoogle Scholar
  23. 23.
    Merrick WC. Mechanism and regulation of eukaryotic protein synthesis. Microbiol Rev 1992; 56:291–315.PubMedGoogle Scholar
  24. 24.
    Richardson A, Semsei I. Effect of aging on translation and transcription. Rev Biol Res Aging 1987; 3:467–83.Google Scholar
  25. 25.
    Merry BJ, Holehan AM. Effect of age and restricted feeding on polypeptide chain assembly kinetics in liver protein synthesis in vivo. Mech Ageing Develop 1991; 58:139–50.CrossRefGoogle Scholar
  26. 26.
    Rattan SIS. Regulation of protein synthesis during ageing. Eur J Gerontol 1992; 1:128–36.Google Scholar
  27. 27.
    Webster GC. Protein synthesis in aging organisms. In: Sohal RS, Birnbaum LS, Cutler RG, editors. Molecular Biology of Aging: Gene Stability and Gene Expression. New York: Raven Press; 1985:263–89.Google Scholar
  28. 28.
    Webster GC. Effect of aging on the components of the protein synthesis system. In: Collatz KG, Sohal RS, eds. Insect Aging. Berlin: Springer-Verlag, 1986:207–16.Google Scholar
  29. 29.
    Takahashi R, Mori N, Goto S. Accumulation of heat-labile elongation factor 2 in the liver of mice and rats. Exp Gerontol 1985; 20:325–31.PubMedCrossRefGoogle Scholar
  30. 30.
    Riis B, Rattan SIS, Derventzi A et al. Reduced levels of ADP-ribosylatable elongation factor-2 in aged and SV40-transformed human cells. FEBS Lett 1990; 266:45–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Rattan SIS, Ward WF, Glenting M et al. Dietary calorie restriction does not affect the levels of protein elongation factors in rat livers during ageing. Mech Ageing Develop 1991; 58:85–91.CrossRefGoogle Scholar
  32. 32.
    Parrado J, Bougria M, Ayala A et al. Effects of aging on the various steps of protein synthesis: fragmentation of elongation factor 2. Free Rad Biol Med 1999; 26:362–70.PubMedCrossRefGoogle Scholar
  33. 33.
    Jäger M, Holtz J, Redpath NT et al. The ageing heart: influence of cellular and tissue ageing on total content and distribution of the variants of elongation factor-2. Mech Ageing Dev 2002; 123:1305–19.PubMedCrossRefGoogle Scholar
  34. 34.
    Soskic V, Groebe K, Schrattenholz A. Nonenzymatic post-translational protein modifications in ageing. Exp Gerontol 2008; 43:247–57.PubMedCrossRefGoogle Scholar
  35. 35.
    Stefani M. Protein folding and misfolding, relevance to disease and biological function. In: Smith HJ, Simons C, Seewell RDE, eds. Protein Misfolding in Neurodegenerative Diseases: Mechanisms and Therapeutic Strategies. Boca Raton: CRC Press, 2008:2–66.Google Scholar
  36. 36.
    Dephoure N, Zhou C, Villén J et al. A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci USA 2008; 105:10762–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Rattan SIS. Cellular senescence in vitro. Encyclopedia of Life Sciences 2008; doi:10.1002/9780470015902. a0002567.pub2.Google Scholar
  38. 38.
    Stein GH, Dulic V. Origins of G1 arrest in senescent human fibroblasts. BioEssays 1995; 17:537–43.PubMedCrossRefGoogle Scholar
  39. 39.
    Tresini M, Lorenzini A, Torres C et al. Modulation of replicative senescence of diploid human cells by nuclear ERK signaling. J Biol Chem 2007; 282:4136–51.PubMedCrossRefGoogle Scholar
  40. 40.
    Sedding DG. FoxO transcription factors in oxidative stress response and ageing—a new fork on the way to longevity? Biol Chem 2008; 389:279–83.PubMedCrossRefGoogle Scholar
  41. 41.
    Riis B, Rattan SIS, Palmquist K et al. Elongation factor 2-specific calcium and calmodulin dependent protein kinase III activity in rat livers varies with age and calorie restriction. Biochem Biophys Res Commun 1993; 192:1210–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Riis B, Rattan SIS, Palmquist K et al. Dephosphorylation of the phosphorylated elongation factor-2 in the livers of calorie-restricted and freely-fed rats during ageing. Biochem Mol Biol Int 1995; 35:855–9.PubMedGoogle Scholar
  43. 43.
    Meinnel T, Mechulam Y, Blanquet S. Aminoacyl-tRNA synthetases: occurrence, structure and function. In: Söll D, RajBhandary UL, eds. tRNA: Structure, Biosynthesis and Function. Washington D.C.: ASM Press, 1995:251–92.Google Scholar
  44. 44.
    Kihara F, Ninomyia-Tsuji J, Ishibashi S et al. Failure in S6 protein phosphorylation by serum stimulation of senescent human diploid fibroblasts, TIG-1. Mech Ageing Dev 1986; 20:305–13.Google Scholar
  45. 45.
    Blumenthal EJ, Miller ACK, Stein GH et al. Serine/threonine protein kinases and calcium-dependent protease in senescent IMR-90 fibroblasts. Mech Ageing Dev 1993; 72:13–24.PubMedCrossRefGoogle Scholar
  46. 46.
    De Tata V, Ptasznik A, Cristofalo VJ. Effect of tumor promoter phorbol 12-myristate 13-acetate (PMA) on proliferation of young and senescent WI-38 human diploid fibroblasts. Exp Cell Res 1993; 205:261–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Farber A, Chang C, Sell C et al. Failure of senescent human fibroblasts to express the insulin-like growth factor-1 gene. J Biol Chem 1993; 268:17883–8.Google Scholar
  48. 48.
    Derventzi A, Rattan SIS, Clark BFC. Phorbol ester PMA stimulates protein synthesis and increases the levels of active elongation factors EF-1a and EF-2 in ageing human fibroblasts. Mech Ageing Dev 1993; 69:193–205.PubMedCrossRefGoogle Scholar
  49. 49.
    Miller RA. Aging and immune function: cellular and biochemical analyses. Exp Gerontol 1994; 29:21–35.PubMedCrossRefGoogle Scholar
  50. 50.
    Pardo VG, Facchinetti MM, Curino A et al. Age-related alteration of 1alpha,25(OH)(2)-vitamin D (3)-dependent activation of p38 MAPK in rat intestinal cells. Biogerontology 2007; 8:13–24.PubMedCrossRefGoogle Scholar
  51. 51.
    Battaini F, Govoni S, Trabucchi M. Protein kinase C signal transmission during aging. In: Macieira-Coelho A, ed. Molecular Basis of Aging. Boca Raton: CRC Press, 1995:269–91.Google Scholar
  52. 52.
    Levine RL. Carbonyl modified proteins in cellular regulation, aging and disease. Free Rad Biol Med 2002; 32:790–6.PubMedCrossRefGoogle Scholar
  53. 53.
    Dukan S, Farewell A, Ballesteros M et al. Protein oxidation in response to increased transcriptional or translational errors. Proc Natl Acad Sci USA 2000; 97:5746–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Grune T. Oxidative stress, aging and the proteasomal system. Biogerontology 2000; 1:31–40.PubMedCrossRefGoogle Scholar
  55. 55.
    Cloos PA, Christgau S. Post-translational modifications of proteins: implications for aging, antigen recognition and autoimmunity. Biogerontology 2004; 5:139–58.PubMedCrossRefGoogle Scholar
  56. 56.
    Perez VI, Buffenstein R, Masamsetti V et al. Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat. Proc Natl Acad Sci USA 2009.Google Scholar
  57. 57.
    Verbeke P, Clark BFC, Rattan SIS. Reduced levels of oxidized and glycoxidized proteins in human fibroblasts exposed to repeated mild heat shock during serial passaging in vitro. Free Rad Biol Med 2001; 31:1593–602.PubMedCrossRefGoogle Scholar
  58. 58.
    Carney JM, Starke-Reed PE, Oliver CN et al. Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone. Proc Natl Acad Sci USA 1991; 88:3633–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Sohal RS, Agarwal S, Dubey A et al. Protein oxidative damage is associated with life expectancy of houseflies. Proc Natl Acad Sci USA 1993; 90:7255–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Sohal RS, Ku H-H, Agarwal S. Biochemical correlates of longevity in two closely related rodent species. Biochem Biophys Res Commun 1993; 196:7–11.PubMedCrossRefGoogle Scholar
  61. 61.
    Beal MF. Oxidatively modified proteins in aging and disease. Free Rad Biol Med 2002; 32:797–803.PubMedCrossRefGoogle Scholar
  62. 62.
    Goto S, Nakamura A, Radak Z et al. Carbonylated proteins in aging and excercise: immunoblot approaches. Mech Ageing Dev 1999; 107:245–53.PubMedCrossRefGoogle Scholar
  63. 63.
    Yasuda K, Adachi H, Fujiwara Y et al. Protein carbonyl accumulation in aging dauer formation-defective (daf ) mutants of Caenorhabditis elegans. J Gerontol Biol Sci 1999; 54A:B47–B51.Google Scholar
  64. 64.
    Gordillo E, Ayala A, Bautista J et al. Implication of lysine residues in the loss of enzymatic activity in rat liver 6-phosphogluconate dehydrogenase found in aging. J Biol Chem 1989; 264:17024–8.PubMedGoogle Scholar
  65. 65.
    Gafni A. Age-related effects in enzyme metabolism and catalysis. Rev Biol Res Aging 1990; 4:315–36.Google Scholar
  66. 66.
    Stadtman ER. Protein oxidation and aging. Science 1992; 257:1220–4.PubMedCrossRefGoogle Scholar
  67. 67.
    Wells-Knecht MC, Huggins TG, Dyer DG et al. Oxidized amino acids in lens protein with age. Measurement of o-tyrosine and dityrosine in the aging human lens. J Biol Chem 1993; 268:12348–52.PubMedGoogle Scholar
  68. 68.
    Mary J, Vougier S, Picot CR et al. Enzymatic reactions involved in the repair of oxidized proteins. Exp Gerontol 2004; 39:1117–23.PubMedCrossRefGoogle Scholar
  69. 69.
    Petropoulos I, Conconi M, Wang X et al. Increase of oxidatively modified protein is associated with a decrease of proteasome activity and content in aging epidermal cells. J Gerontol Biol Sci 2000; 55A:B220–B7.Google Scholar
  70. 70.
    Wood JM, Decker H, Hartmann H et al. Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunting methionine sulfoxide repair. FASEB J 2009.Google Scholar
  71. 71.
    Ruan H, Tang XD, Chen ML et al. High-quality life extension by the enzyme peptide methionine sulfoxide reductase. Proc Natl Acad Sci USA. 2002; 99:2748–53.PubMedCrossRefGoogle Scholar
  72. 72.
    Meli M, Frey J, Perier C. Native protein glycoxidation and aging. J Nutr Health Aging 2003; 7:263–6.PubMedGoogle Scholar
  73. 73.
    Ramasamy R, Yan SF, Schmidt AM. Methylglyoxal comes of AGE. Cell 2006; 124:258–60.PubMedCrossRefGoogle Scholar
  74. 74.
    Kueper T, Grune T, Prahl S et al. Vimentin is the specific target in skin glycation. Structural prerequisites, functional consequences and role in skin aging. J Biol Chem 2007; 282:23427–36.PubMedCrossRefGoogle Scholar
  75. 75.
    Oimomi M, Maeda Y, Hata F et al. A study of the age-related acceleration of glycation of tissue proteins in rats. J Gerontol 1988; 43:B98–101.PubMedGoogle Scholar
  76. 76.
    Miksík I, Deyl Z. Changes in the amount of e-hexosyllysine, UV absorbance and fluorescence of collagen with age in different animal species. J Gerontol 1991; 46:B111–6.PubMedGoogle Scholar
  77. 77.
    Lee AT, Cerami A. Role of glycation in aging. Ann NY Acad Sci 1992; 663:63–70.PubMedCrossRefGoogle Scholar
  78. 78.
    Makita Z, Vlassara H, Rayfield E et al. Hemoglobin-AGE: a circulating marker of advanced glycosylation. Science 1992; 258:651–3.PubMedCrossRefGoogle Scholar
  79. 79.
    Gracy RW, Yüksel KÜ, Chapman ML et al. Impaired protein degradation may account for the accumulation of “abnormal” proteins in aging cells. In: Adelman RC, Dekker EE, eds. Modifications of Proteins during Aging. New York: Alan R. Liss, 1985:1–18.Google Scholar
  80. 80.
    Cini JK, Gracy RW. Molecular basis of the isozyme of bovine glucose-6-phosphate isomerase. Arch Biochem Biophys 1986; 249:500–5.PubMedCrossRefGoogle Scholar
  81. 81.
    Brunauer LS, Clarke S. Age-dependent accumulation of protein residues which can be hydrolyzed to d-aspartic acid in human erythrocytes. J Biol Chem 1986; 261:12538–43.PubMedGoogle Scholar
  82. 82.
    Luthra M, Ranganathan D, Ranganathan S et al. Racemization of tyrosine in the insoluble protein fraction of brunescent aging human lenses. J Biol Chem 1994; 269:22678–82.PubMedGoogle Scholar
  83. 83.
    Beneke S, Alvarez-Gonzalez R, Bürkle A. Comparative characterization of poly(ADP-ribose) polymerase-1 from two mammalian species with different life span. Exp Gerontol 2000; 35:989–1002.PubMedCrossRefGoogle Scholar
  84. 84.
    Bürkle A. Physiology and pathophysiology of poly(ADP-ribosyl)ation. BioEssays 2001; 23:795–806.PubMedCrossRefGoogle Scholar
  85. 85.
    Dell’Orco RT, Anderson LE. Decline of poly(ADP-ribosyl)ation during in vitro senescence in human diploid fibroblasts. J Cell Physiol 1991; 146:216–21.PubMedCrossRefGoogle Scholar
  86. 86.
    Grube K, Bürkle A. Poly(ADP-ribose) polymerase activity in mononuclear leukocytes of 13 mammalian species correlates with species-specific life span. Proc Natl Acad Sci USA 1992; 89:11759–63.PubMedCrossRefGoogle Scholar
  87. 87.
    McBride AE, Silver PA. State of the Arg: protein methylation at arginine comes of age. Cell 2001; 106:5–8.PubMedCrossRefGoogle Scholar
  88. 88.
    Rattan SIS, Derventzi A, Clark BFC. Protein synthesis, post-translational modifications and aging. Ann NY Acad Sci 1992; 663:48–62.PubMedCrossRefGoogle Scholar
  89. 89.
    Mays-Hoopes LL. Macromolecular methylation during aging. Rev Biol Res Aging 1985; 2:361–93.Google Scholar
  90. 90.
    McFadden PN, Clarke S. Protein carboxyl methyltransferase and methyl acceptor proteins in aging and cataractus tissue of the human eye lens. Mech Ageing Develop 1986; 34:91–105.CrossRefGoogle Scholar
  91. 91.
    Sellinger OZ, Kramer CM, Conger A et al. The carboxylmethylation of cerebral membrane-bound proteins increases with age. Mech Ageing Develop 1988; 43:161–73.CrossRefGoogle Scholar
  92. 92.
    Kay MMB. Molecular aging of membrane molecules and cellular removal. In: Goldstein AL, ed. Biomedical Advances in Aging. New York: Plenum Press, 1990:147–61.Google Scholar
  93. 93.
    Porter MB, Pereira-Smith OM, Smith JR. Common senescent cell-specific antibody epitopes on fibronectin in species and cells of varied origin. J Cell Physiol 1992; 150:545–51.PubMedCrossRefGoogle Scholar
  94. 94.
    Hébert L, Pandey S, Wang E. Commitment to cell death is signaled by the appearance of a terminin protein of 30 kDa. Exp Cell Res 1994; 210:10–8.PubMedCrossRefGoogle Scholar
  95. 95.
    Selkoe DJ. Aging brain, aging mind. Sci Amer 1992; 267:135–42.CrossRefGoogle Scholar
  96. 96.
    Esler WP, Wolfe MS. A portrait of Alzheimer secretases—new features and familiar faces. Science 2001; 293:1449–54.PubMedCrossRefGoogle Scholar
  97. 97.
    DiPaolo BR, Pignolo RJ, Cristofalo VJ. Overexpression of the two-chain form of cathepsin B in senescent WI-38 cells. Exp Cell Res 1992; 201:500–5.PubMedCrossRefGoogle Scholar
  98. 98.
    Sottile J, Mann DM, Diemer V et al. Regulation of collagenase and collagenase mRNA production in early-and late-passage human diploid fibroblasts. J Cell Physiol 1989; 138:281–90.PubMedCrossRefGoogle Scholar
  99. 99.
    Whiteheart SW, Shenbagamurthi P, Chen L et al. Murine elongation factor 1a (EF-1a) is post-translationally modified by novel amide-linked ethanolamine-phosphoglycerol moieties. J Biol Chem 1989; 264:14334–41.PubMedGoogle Scholar
  100. 100.
    Park MH, Wolff EC, Folk JE. Is hypusine essential for eukaryotic cell proliferation? TIBS 1993; 18:475–9.PubMedGoogle Scholar
  101. 101.
    Nagaraj RH, Sell DR, Prabhakaram M et al. High correlation between pentosidine protein crosslinks and pigmentation implicates ascorbate oxidation in human lens senescence and cataractogenesis. Proc Natl Acad Sci USA 1991; 88:10257–61.PubMedCrossRefGoogle Scholar
  102. 102.
    Norsgaard H, Clark BFC, Rattan SIS. Distinction between differentiation and senescence and the absence of increased apoptosis in human keratinocytes undergoing cellular aging in vitro. Exp Gerontol 1996; 31:563–70.PubMedCrossRefGoogle Scholar
  103. 103.
    Huttner WB. Protein tyrosine sulfation. TIBS 1987; 12:361–3.Google Scholar
  104. 104.
    Marshall CJ. Protein prenylation: a mediator of protein-protein interactions. Science 1993; 259:1865–6.PubMedCrossRefGoogle Scholar
  105. 105.
    Thelin A, Runquist M, Ericsson J et al. Age-dependent changes in rat liver prenyltransferases. Mech Ageing Dev 1994; 76:165–76.PubMedCrossRefGoogle Scholar
  106. 106.
    Merker K, Grune T. Proteolysis of oxidised proteins and cellular senescence. Exp Gerontol 2000; 35:779–86.PubMedCrossRefGoogle Scholar
  107. 107.
    Gaczynska M, Osmulski PA, Ward WF. Caretaker or undertaker? The role of the proteasome in aging. Mech Ageing Dev 2001; 122:235–54.PubMedCrossRefGoogle Scholar
  108. 108.
    Shringaarpure R, Davies KJA. Protein turnover by the proteasome in aging and disease. Free Rad Biol Med 2002; 32:1084–9.CrossRefGoogle Scholar
  109. 109.
    Pan J-X, Short SR, Goff SA et al. Ubiquitin pools, ubiquitin mRNA levels and ubiquitin-mediated proteolysis in aging human fibroblasts. Exp Gerontol 1993; 28:39–49.PubMedCrossRefGoogle Scholar
  110. 110.
    Bulteau AL, Petropoulos I, Friguet B. Age-related alterations of proteasome structure and function in aging epidermis. Exp Gerontol 2000; 35:767–77.PubMedCrossRefGoogle Scholar
  111. 111.
    Brégégére F, Milner Y, Friguet B. The ubiquitin-proteasome system at the crossroads of stress-response and ageing pathways: a handle for skin care? Aging Res Rev 2006; 5:60–90.CrossRefGoogle Scholar
  112. 112.
    Carrard G, Bulteau AL, Petropoulos I et al. Impairment of proteasome structure and function in aging. Int J Biochem Cell Biol 2002; 34:1461–74.PubMedCrossRefGoogle Scholar
  113. 113.
    Terman A, Kurz T, Gustafsson B et al. Lysosomal labilization. IUBMB LIfe 2006; 58:531–9.PubMedCrossRefGoogle Scholar
  114. 114.
    Terman A, Gustafsson B, Brunk UT. Autophagy, organelles and ageing. J Pathol 2007; 211:134–43.PubMedCrossRefGoogle Scholar
  115. 115.
    Wick M, Bürger C, Brüsselbach S et al. A novel member of human tissue inhibitor of metalloproteinases (TIMP) gene family is regulated during G1 progression, mitogenic stimulation, differentiation and senescence. J Biol Chem 1994; 269:18953–60.PubMedGoogle Scholar
  116. 116.
    Hearn MG, Edland SD, Ogburn CE et al. Trypsin inhibitor activities of fibroblasts increase with age of donor and are unaltered in familial Alzheimer’s disease. Exp Gerontol 1994; 29:611–23.PubMedCrossRefGoogle Scholar
  117. 117.
    Rattan SIS. Theories of biological aging: genes, proteins and free radicals. Free Rad Res 2006; 40:1230–8.CrossRefGoogle Scholar
  118. 118.
    Rattan SIS. Increased molecular damage and heterogeneity as the basis of aging. Biol Chem 2008; 389:267–72.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  • Suresh I. S. Rattan
    • 1
  1. 1.Laboratory of Cellular Aging, Department of Molecular BiologyAarhus UniversityAarhus-CDenmark

Personalised recommendations