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Dtsch Med Wochenschr 2004; 129(16): 903-907
DOI: 10.1055/s-2004-823037
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Geriatrie / Grundlagenforschung
© Georg Thieme Verlag Stuttgart · New York

Molekulare Mechanismen für die Kontrolle der Lebenserwartung

Molecular mechanisms regulating liefe-expectancyS. Nikolaus1 , S. Schreiber1
  • 1Klinik für Allgemeine Innere Medizin Universitätsklinikum Schleswig-Holstein, Campus Kiel
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Publication History

eingereicht: 8.12.2003

akzeptiert:18.3.2004

Publication Date:
08 April 2004 (online)

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In den letzten Jahrzehnten ist es zu einem dramatischen Anwachsen der Weltbevölkerung gekommen. Dabei wächst der relative Anteil der älteren Bevölkerung stetig an. So kommt es sowohl zu einem Anstieg der absoluten Anzahl als auch des prozentualen Anteils alter Menschen.

Diese Entwicklung kann ausschließlich durch Faktoren im Lebensstil wie z. B. eine gesündere Ernährung, bessere hygienische Bedingungen oder verbesserte therapeutische Möglichkeiten bei der Behandlung bestimmter Erkrankungen erklärt werden. Das nominale Lebensalter scheint jedoch nur ein ungenügendes Maß zur Bestimmung des biologischen Alters eines Menschen: Zwei Individuen können trotz identischem Lebensalter und identischem Lebensstil ein deutlich unterschiedliches biologisches Alter und damit auch möglicherweise eine unterschiedliche Lebenserwartung aufweisen. Diese Arbeit wird kursorisch verschiedene molekulare Mechanismen beleuchten, die in die Kontrolle des Alterungsprozesses involviert sind.

Literatur

  • 1 Andersen-Ranberg K, Christensen K, Jeune B. et al . Declining physical abilities with age: a cross-sectional study of older twins and centenarians in Denmark.  Age and Ageing. 1999;  28 373-377
    Search in Google Scholar
  • 2 Berlett B S, Stadtman E R. Protein oxidation in aging, disease and oxidative stress.  J Biol Chem. 1997;  272 20313-20316
    Search in Google Scholar
  • 3 Blackman M R, Sorkin J D, Munzer T. et al . Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial.  JAMA. 2000;  288 2282-2292
    Search in Google Scholar
  • 4 Cawthon R M, Smith K R, O’Brien E. et al . Association between telomere length in blood and mortality in people aged 60 years or older.  Lancet. 2003;  361 393-395
    Search in Google Scholar
  • 5 Finch C E, Tanzi R E. Genetics of aging.  Science. 1997;  278 407-411
    Search in Google Scholar
  • 6 Floyd R A. Oxidative damage to behaviour during aging.  Science. 1991;  245 1597
    Search in Google Scholar
  • 7 Flurkey K, Papaconstantinou J, Harrison D E. The Snell dwarf mutation Pit1 (dw) can increase life-span in mice.  Mech Ageing Dev. 2002;  123 121-130
    Search in Google Scholar
  • 8 Garasto S, Rose G, Derango F. et al . The study of APOA1, APOC3 and APOA4 variability in healthy ageing people reveals another paradox in the oldest old subjects.  Ann Hum Genet. 2003;  67 54-62
    Search in Google Scholar
  • 9 Goldstein S, Murano S, Benes H. et al . Studies on the molecular-genetic basis of replicative senescence in Werner syndrome and normal fibroblasts.  Exp Gerontol. 1989;  24 461-468
    Search in Google Scholar
  • 10 Greider C W, Blackburn E H. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts.  Cell. 1985;  43 405-413
    Search in Google Scholar
  • 11 Greider C W. Telomeres and senescence: the history, the experiment, the future.  Curr Biol. 1998;  8 R178-R181
    Search in Google Scholar
  • 12 Harman D. Aging: a theory based on free radicals and radiation chemistry.  J Gerontol. 1956;  11 298-300
    Search in Google Scholar
  • 13 Harman D. The aging process.  Proc Natl Acad Sci U S A. 1981;  78 7124-7128
    Search in Google Scholar
  • 14 Hayflick L. The limited in vitro lifetime of human diploid cell strains.  Exp Cell Res. 1965;  37 614-636
    Search in Google Scholar
  • 15 Herskind A M, McGue M, Holm N V. et al . The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870 - 1900.  Hum Genet. 1996;  97 319-323
    Search in Google Scholar
  • 16 Jazwinski S M. Longevity, genes and aging.  Science. 1996;  273 54-59
    Search in Google Scholar
  • 17 Kaeberlein M, McVey M, Guarente L. Using yeast to discover the fountain of youth. Washington (DC): American Association for the Advancement of Science; New Findings Perspectives In: Science of aging and knowledge enviroment;http//sageke.sciencemag.org/cgi/content/full/sageke;2001/1/pel 2001
    Search in Google Scholar
  • 18 Kang M K, Swee J, Kim R H. et al . The telomeric length and heterogeneity decrease with age in normal human oral keratinocytes.  Mech Ageing Dev. 2002;  123 585-592
    Search in Google Scholar
  • 19 Kannisto V. Development of Oldest-Old Mortality, 1950 - 1990: evidence from 28 developed countries. Odense:Univ. Press Odense Monographs on Population Aging 1 1994
    Search in Google Scholar
  • 20 Lin Y J, Seroude L, Benzer S. Extended life-span and stress resistance in the Drosophila mutant Methuselah.  Science. 1998;  282 943-946
    Search in Google Scholar
  • 21 Ljungquist B, Berg S, Lanke J. et al . The effect of genetic factors for longevity: a comparison of identical and fraternal twins in the Swedish Twin Registry.  J Gerontol A Biol Sci Med Sci. 1998;  53 M441-M446
    Search in Google Scholar
  • 22 Lithgow G J, Andersen J K. The real Dorian Gray mouse.  Bioessays. 2000;  22 410-413
    Search in Google Scholar
  • 23 Masoro E J. Dietary restriction and aging.  J Am Geriatr Soc. 1993;  41 994-999
    Search in Google Scholar
  • 24 McCall M R, Frei B. Can antioxidant vitamins maternally reduce oxidative damage in humans?.  Free Radical Biol Med. 1999;  26 1034-1053
    Search in Google Scholar
  • 25 McCarter R, Masoro E J, Yu B P. Does food restriction retard aging by reducing the metabolic rate?.  Am Physiol. 1985;  248 E488-E490
    Search in Google Scholar
  • 26 Meydani M. Nutrition interventions in aging and age-associated disease.  Ann N Y Acad Sci. 2001;  928 226-235
    Search in Google Scholar
  • 27 Mitnitski A B, Graham J E, Mogilner A J. et al . Frailty, fitness and late-life mortality in relation to chronological and biological age.  BMC Geriatr. 2002;  2 1
    Search in Google Scholar
  • 28 Murakami S, Johnson T E. A genetic pathway conferring life extension and resistance to UV stress in Caenorhadtitis elegans.  Genetics. 1996;  143 1207-1218
    Search in Google Scholar
  • 29 Oeppen J, Vaupel J W. Broken limits to life expectancy.  Science. 2002;  296 1029-1030
    Search in Google Scholar
  • 30 Olovnikov A M. A theory of marginotomy:The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon.  J Theor Biol. 1973;  41 181-190
    Search in Google Scholar
  • 31 Orr W C, Chen C N> L. Aging and neural control of the GI tract: IV. Clinical and physiological aspects of gastrointestinal motility and aging.  Am J Physiol Gastrointest Liver Physiol. 2002;  283 G1226-1231
    Search in Google Scholar
  • 32 Orr W C, Sohal R S. Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster.  Science. 1994;  263 1128-1130
    Search in Google Scholar
  • 33 Ozawa T. Genetic and functional changes in mitochondria associated with aging.  Physiol Rev. 1997;  77 425-464
    Search in Google Scholar
  • 34 Perls T, Levenson R, Regan M. et al . What does it take to live 100?.  Mech Ageing Dev. 2002;  123 231-242
    Search in Google Scholar
  • 35 Puca A A, Daly M J, Brewster S J. et al . A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4.  PNAS. 2001;  98 10505-10508
    Search in Google Scholar
  • 36 Rodriguez-Martinez M A, Izaguirre J, Ruiz-Torres A. Oxidative detoxification capacity with aging and after the intake of peroxidised oil years ago.  Horm Metab Res. 1991;  23 46-47
    Search in Google Scholar
  • 37 Roberts T W, Smith J R. The proliferation potential of chick embryo fibroblasts: population doublings vs. time culture.  Cell Biol Int Rep. 1980;  4 1057-1063
    Search in Google Scholar
  • 38 Rogina B, Reenan R A, Nilsen S P. et al . Extendes life-span conferred by cotransporter gene mutations in Drosophila.  Science. 2000;  290 2137-2140
    Search in Google Scholar
  • 39 Rudman D, Feller A G, Nagraj H S. et al . Effects of human growth hormone in men over 60 years old.  N Engl J Med. 1990;  323 1-6
    Search in Google Scholar
  • 40 Shay J W, Wright W E. Hayflick, his limit and cellular aging.  Nature Rev Mol Cell Biol. 2000;  1 72-76
    Search in Google Scholar
  • 41 Sohal R S, Svensson I, Sohal B H. et al . Superoxide anion radical production in different species.  Mech Ageing Dev. 1989;  49 129-135
    Search in Google Scholar
  • 42 Sohal R S, Weindruch R. Oxidative stress, caloric restriction and aging.  Science. 1996;  273 59-63
    Search in Google Scholar
  • 43 Schachter F, Faure-Delanef L, Guenot F. et al . Genetic associatios with human longevity and the ApoE and ACE loci.  Nat Genet. 1994;  6 29-32
    Search in Google Scholar
  • 44 Schneider E L, Mitsui Y. The relationship between in vitro cellular aging and in vivo human age.  Proc Natl Acad Sci U S A. 1976;  73 3584-3588
    Search in Google Scholar
  • 45 Urquidi V, Tarin D, Goodison S. Role of telomerase in cell senescence and oncogenesis.  Annu Rev Med. 2000;  51 65-79
    Search in Google Scholar
  • 46 Vaupel J W, Carey J R, Christensen K. et al . Biodemographic trajectories of longevity.  Science. 1998;  20 855-860
    Search in Google Scholar
  • 47 Vaupel J W. Inherited frailty and longevity.  Demography. 1988;  25 277-287
    Search in Google Scholar
  • 48 Vaupel J W, Jeune B. Exceptional Longevity: From Prehistory to the present. Odense: Univ. Press 1996: 109
    Search in Google Scholar
  • 49 Wallace D C. Mitochondrial genetics: a paradigm for aging and degenerative diseases?.  Science. 1992;  256 628-623
    Search in Google Scholar
  • 50 Weindruch R, Walford R L. Dietary restriction in mice beginning at 1 year of age: effect of life-span and spontaneous cancer incidence.  Science. 1982;  215 1415-1418
    Search in Google Scholar

Prof. Dr. med. Stefan Schreiber

Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Allgemeine Innere Medizin, 1.Medizinische Klinik

Schittenhelmstraße 12

24114 Kiel