Biogerontology

, Volume 3, Issue 5, pp 307–316 | Cite as

Accumulation of insoluble protein and aging

  • Anund Hallén
Article

Abstract

It is proposed that biological aging mainly depends on a deleterious accumulation of insoluble inert protein that has escaped physiological proteolytic degradation. Intracellularly, a three-dimensional network of polypeptide chains may exclude macromolecular structures and organelles from part of the cytosolic water. In this way vital intracellular transport mechanisms may be obstructed, providing a rationale to several observations linked to aging.

aging exclusion insoluble protein polypeptide net work 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Angello JC, Pendergrass WR, Norwood TH and Prothero J (1989) Cell enlargement: one possible mechanism underlying cellular senescence. J Cell Physiol 140: 288-294PubMedCrossRefGoogle Scholar
  2. Bilder D, Li M and Perrimon N (2000) Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science 289: 113-116PubMedCrossRefGoogle Scholar
  3. Bjorksten J (1958) A common molecular basis for the aging syndrome. J Am Ger Soc 6: 740-749Google Scholar
  4. Bodnar AG et al. (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279: 349-352PubMedCrossRefGoogle Scholar
  5. Brun A and Brunk U (1970) Histochemical indications for lysosomal localization of heavy metals in normal rat brain and liver. J Histochem Cytochem 18: 820-827PubMedGoogle Scholar
  6. Cerami AJ (1985) Hypothesis. Glucose as a mediator of aging. J Am Ger Soc 33: 626-634Google Scholar
  7. Driver C (2001) The Gompertz function does not measure ageing. Biogerontology 2: 61-65PubMedCrossRefGoogle Scholar
  8. Duesberg P (1999) Are centrosomes or aneuploidy the key to cancer? Science 284: 2091-2092PubMedCrossRefGoogle Scholar
  9. Failla G (1958) The aging process and cancerogenesis. Ann N Y Acad Sci 721: 1124-1140Google Scholar
  10. Fujii N, Satoh K, Harada K and Ishibashi Y (1994) Simultaneous stereoinversion and isomerization at specific aspartic acid residues in ?A-crystallin from human lens. J Biochem 116: 663-669PubMedGoogle Scholar
  11. Goldstein S, Stotland D and Cordeiro RAJ (1976) Decreased proteolysis and increased amino acid efflux in aging human fibroblasts. Mech Ageing Dev 5: 221-233PubMedCrossRefGoogle Scholar
  12. Gompertz B (1825) On the nature of the function expressive of the law of human mortality, and on a new mode of determining the value of life contingencies. Philosophical Transactions of the Royal Society (London), Series A 115: 513-585Google Scholar
  13. Gross J (1960) The properties of some soluble components of connective tissue and the influence of growth rate. In: Strehler et al. (eds) The Biology of Aging, pp 192-195. American Institute of Biological Sciences, Washington, DCGoogle Scholar
  14. Grune T (2000) Oxidative stress, aging and the proteasomal system. Biogerontology 1: 31-40PubMedCrossRefGoogle Scholar
  15. Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW and Weinberg RA (1999) Creation of human tumour cells with defined genetic elements. Nature 400: 464-468PubMedCrossRefGoogle Scholar
  16. Hallén A (1962) Collagen and ground substance of human interverteberal disc. Acta Chem Scand 62: 705-710CrossRefGoogle Scholar
  17. Hallén A (1986) Aging of the human intervertebral disc. 8th Scand Congr Gerontol (Tampere) Proc: 267-269Google Scholar
  18. Hallén, A (1999) Accumulation of protein in aging. 4th European Congress of Gerontology. Z Gerontol Geriatrics 32, Suppl 2, Abstr 456Google Scholar
  19. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11: 298-300PubMedGoogle Scholar
  20. Harman D (1981) The aging process. Proc Natl Acad Sci USA 78: 7124-7128PubMedCrossRefGoogle Scholar
  21. Harman D (2001) Aging: overview. Ann N Y Acad Sci 928: 1-21PubMedCrossRefGoogle Scholar
  22. Häussinger D, Roth E, Lang F and Gerok W (1993) Cellular hydration state: an important determinant of protein catabolism in health and disease. Lancet 341: 1330-1332PubMedCrossRefGoogle Scholar
  23. Hayflick L (1996) How and Why we Age. Pocket edition. Ballantine Books, New YorkGoogle Scholar
  24. Hayflick L and Moorehead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25: 585-593CrossRefGoogle Scholar
  25. Herzfeld E and Klinger R (1917) Chemische Studien zur Physiologie und Pathologie 1. Eiweiss-chemische Grundlagen der Lebensvorgänge. Biochem Z 83: 42-61Google Scholar
  26. Hipkiss AR, Brownson C and Carrier MJ (2001) Carnosine, the antiageing, antioxidant dipeptide, may react with protein carbonyl groups. Mech Ageing Dev 122: 1431-1445PubMedCrossRefGoogle Scholar
  27. Hjertén S (1962) Chromatographic separation according to size of macromolecules and cell particles on columns of agarose suspensions. Arch Biochem Biophys 99: 466-475PubMedCrossRefGoogle Scholar
  28. Hoenders HJ and Bloemendal H (1983) Lens proteins and aging. J Gerontol 38: 278-286PubMedGoogle Scholar
  29. Johansson C, Black D, Johnell O, Odén A and Mellström D (1998) Bone mineral density is a predictor of survival. Calcif Tissue Int 63: 190-196PubMedCrossRefGoogle Scholar
  30. Jones HB (1956) A special consideration of the aging process, disease and life expectancy. Adv Biol Med Phys 4: 281-337PubMedGoogle Scholar
  31. Kennedy BK, Austriaco Jr NR and Guarente L (1994) Daughter cells of saccharomyces cerevisiae from old mothers display a reduced life span. J Cell Biol 127: 1985-1993PubMedCrossRefGoogle Scholar
  32. Kim JH, Choy HE, Nam KH and Park SC (2001) Transglutaminasemediated crosslinking of specific core histone subunits and cellular senescence. Ann N Y Acad Sci 928: 65-70PubMedCrossRefGoogle Scholar
  33. Kipling D and Cooke HJ (1990) Hypervariable ultra-long telomeres in mice. Nature 347: 400-402PubMedCrossRefGoogle Scholar
  34. Ku H-H, Brunk UT and Sohal RS (1993) Relationship between mitochondrial superoxide and hydrogen peroxide production and longevity of mammalian species. Free Radical Biol Med 15: 621-627CrossRefGoogle Scholar
  35. Lansing AI (1947a) A transmissible, cumulative, and reversible factor in aging. J Gerontol 2: 228-239PubMedGoogle Scholar
  36. Lansing AI (1947b) The general physiology of aging-A review. J Gerontol 2: 327-338PubMedGoogle Scholar
  37. Laurent TC (1963) The interaction between polysaccharides and other macromolecules 5. The solubility of proteins in the presence of dextran. Biochem J 89: 253-257PubMedGoogle Scholar
  38. Laurent TC (1964) The interaction between polysaccharides and other macromolecules 9. The exclusion of molecules from hyaluronic acid gels and solutions. Biochem J 93: 106-112PubMedGoogle Scholar
  39. Laurent TC and Killander J (1964) A theory of gel filtration and its experimental verification. J Chromatogr 14: 317-330CrossRefGoogle Scholar
  40. Lengauer C, Kinzler KW and Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396: 643-649PubMedCrossRefGoogle Scholar
  41. Lim IK, Hong KW, Kwak IH, Yoon G and Park SC (2001) Translocation inefficiency of intracellular proteins in senescence of human diploid fibroblasts. Ann N Y Acad Sci 928: 176-181PubMedCrossRefGoogle Scholar
  42. Lutz HU, Bussolino F, Flepp R, Fasler S, Stammler P, Kazatchkine MD and Arese P (1987) Naturally occuring anti-band-3 antibodies and complement together mediate phagocytosis of oxidatively stressed human erythrocytes. Proc Natl Acad Sci USA 84: 7368-7372PubMedCrossRefGoogle Scholar
  43. Macieira-Coelho A (1966) Action of cortisone on human fibroblasts in vitro. Experentia 22: 390-391CrossRefGoogle Scholar
  44. Masoro EJ, Yo BP and Bertrand HA (1982) Action of food restriction in delaying the aging process. Proc Natl Acad Sci USA 79: 4239-4241PubMedCrossRefGoogle Scholar
  45. Masoro EJ (1993) Dietary restriction and aging. J Am Ger Soc 41: 994-999Google Scholar
  46. Masters PM, Bada JL and Zigler Jr JS (1978) Aspartic acid racemization in heavy molecular weight crystallins and waterinsoluble protein from normal human lenses and cataracts. Proc Natl Acad Sci USA 75: 1204-1208Google Scholar
  47. McCarter RJ and Palmer J (1992) Energy metabolism and aging: a lifelong study of Fischer 344 rats. Am J Physiol 263: E448-E452PubMedGoogle Scholar
  48. McCay CM, Crowell MF and Maynard LA (1935) The effect of retarded growth upon the length of life span and upon the ultimate body size. J Nutrition 10: 63-79Google Scholar
  49. Morris CJOR and Morris P (1971) Molecular-sieve chromatography and electrophoresis in polyacrylamide gels. Biochem J 124: 517-528PubMedGoogle Scholar
  50. Ogston AG (1958) The spaces in a uniform random suspension of fibres. Trans Faraday Soc 54: 1754-1757CrossRefGoogle Scholar
  51. Orr-Weaver TL and Weinberg RA (1998) A checkpoint on the road to cancer. Nature 392: 223-224PubMedCrossRefGoogle Scholar
  52. Peifer M (2000) Travel bulletin-traffic jams cause tumors. Science 289: 67-69PubMedCrossRefGoogle Scholar
  53. Rasoamanantena P, Labat-Robert J and Goldstein S (1993) Variations de la biosynthèse et quantification de l'ARNm de la fibronectine humaine au cours du vieillissement en culture. C R Soc Biol 187: 238-246Google Scholar
  54. Robert L and Labat-Robert J (2000) Aging of connective tissues: from genetic to epigenetic mechanisms. Biogerontology 1: 123-131PubMedCrossRefGoogle Scholar
  55. Röhme D (1981) Evidence for a relationship between longevity of mammalian species and life spans of normal fibroblasts in vitro and erythrocytes in vivo. Proc Natl Acad Sci USA 78: 5009-5013PubMedCrossRefGoogle Scholar
  56. Rosenberger RF (1991) Senescence and the accumulation of abnormal proteins. Mutat Res 256: 255-262PubMedGoogle Scholar
  57. Schliwa M, van Blerkom J and Porter KR (1981) Stabilization of the cytoplasmic ground substance in detergent-opened cells and structural and biochemical analysis of its composition. Proc Natl Acad Sci 78: 4329-4333PubMedCrossRefGoogle Scholar
  58. Sohal RS and Weindruch R (1996) Oxidative stress, caloric restriction, and aging. Science 273: 59-63PubMedGoogle Scholar
  59. Stadtman ER (1992) Protein oxidation and aging. Science 257: 1220-1224PubMedGoogle Scholar
  60. Stadtman ER (2001) Protein oxidation in aging and age-related diseases. Ann N Y Acad Sci 928: 22-38PubMedCrossRefGoogle Scholar
  61. Strehler BL (1977) Time Cells and Aging, 2nd edn. Academic Press Strehler BL and Mildvan AS (1960) General theory of mortality and aging. Science 132: 14-21Google Scholar
  62. Terman A and Brunk UT (1998) Lipofuscin: mechanisms of formation and increase with age. APMIS 106: 265-276PubMedCrossRefGoogle Scholar
  63. Tyner SD et al. (2002) p53 mutant mice that display early ageingassociated phenotypes. Nature 415: 45-53PubMedCrossRefGoogle Scholar
  64. Vaupel JW et al. (1998) Biodemographic trajectories of longevity. Science 280: 855-860PubMedCrossRefGoogle Scholar
  65. Verzár F (1958) Problems of general biology of aging. J Gerontol 1(Suppl): 6-16Google Scholar
  66. Verzár F (1963) The aging of collagen. Sci Am 208 (4): 104-114PubMedCrossRefGoogle Scholar
  67. Vrieling H (2001) Mitotic maneuvers in the light. Nature Genet 28: 101-102PubMedCrossRefGoogle Scholar
  68. Vorobtsova I, Semenov A, Timofeyeva N, Kanayeva A and Zvereva I (2001) An investigation of the age-dependency of chromosome abnormalities in human populations exposed to low-dose ionising radiation. Mech Ageing Dev 122: 1373-1382PubMedCrossRefGoogle Scholar
  69. Wang K-M, Rose NR, Bartholomew EA, Balzer M, Berde K and Foldvary M (1970) Changes of enzymic activities in human diplod cell line WI-38 at various passages. Exp Cell Res 61: 357-364PubMedCrossRefGoogle Scholar
  70. Yu C-E et al. (1996) Positional cloning of the Werner syndrome gene. Science 272: 258-262PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Anund Hallén
    • 1
  1. 1.Department of Medical Biochemistry and MicrobiologyUniversity of Uppsala, Biomedical CenterUppsalaSweden

Personalised recommendations