Cellular Aging

  • Thomas H. Norwood


The level of investigative activity into the mechanisms of aging at the cellular and molecular level has increased dramatically during the past two to three decades. While these efforts certainly have yielded a wealth of descriptive information and some fundamental changes in our perception of the aging process, definitive knowledge of the cause or causes of aging remains elusive. Investigative efforts in the area of cellular aging address a number of questions, the answers to which are only beginning to emerge. For example, it is not known if all cell populations in the body are vulnerable to aging, or if the nature of the aging process is similar in all cell populations in the body. Some scientists have suggested that the rate of aging is determined by one or a few critical cell populations; an alternative notion is that the manifestations of aging are the summation of subtle decrements of function in most or all of the cell populations in the body. Also, the role of aging at the cellular level in the pathogenesis of age-associated diseases, such as arteriosclerotic vascular disease and many carcinomas, remain, for the most part, speculative. While definitive answers to the questions posed above are not forthcoming at the present time, there is enough information to permit some speculation about future directions that may be pursued in the area of cellular aging. In this chapter, the current status of cellular aging will be discussed at a level that will provide geriatricians with a foundation of knowledge to assist them in following future developments in the field of basic gerontology.


Cellular Aging Senescent Cell Fibroblast Culture Maximum Life Span Human Diploid Cell Strain 
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.
    Harrison DE. Experience with developing assays of physiological age. In: Reff ME, Schneider EL, eds. Biomarkers of Aging. Bethesda, MD:; 1981:2–12. Na- 14. tional Institutes of Heatlh publication NIH 82–2221.Google Scholar
  2. 2.
    Carrel A. Man, the Unknown. New York, NY: Halycyon House; 1935: 173.Google Scholar
  3. 3.
    Hayflick L, Moorhead P$. The serial cultivation of 15. human diploid cell strains. Exp Cell Res 1961; 25: 585–621.PubMedCrossRefGoogle Scholar
  4. 4.
    Hayflick L. The limited in vitro lifetime of human diploid 16. cell strains. Exp Cell Res 1965; 37: 614–636.PubMedCrossRefGoogle Scholar
  5. 5.
    Martin GM, Sprague CA, Epstein CJ. Replicative life-span of cultivated human cells. effects of donor’s age, tissue, and genotype. Lab Invest 1970; 23: 86–92.PubMedGoogle Scholar
  6. 6.
    Martin GM, Ogburn CE, Sprague CA. Effects of age on cell division capacity. In: Danon D, Shock NW, Marois M, eds. Aging: A Challenge to Science and Society. New York, NY: Oxford University Press Inc; 1981; 1: 124–135.Google Scholar
  7. 7.
    Goldstein S. Human genetic disorders that feature premature onset and accelerated progression of biological aging. In: Schneider EL, ed: The Genetics of Aging. New York, NY: Plenum Publishing Corp; 1978: 171–224.CrossRefGoogle Scholar
  8. 8.
    Rohme D. Evidence for a relationship between longevity of mammalian species and life-spans of normal fibroblasts in vitro and erythrocytes in vitro. Proc Natl Acad Sci USA 1980; 78: 5009–5013.CrossRefGoogle Scholar
  9. 9.
    Schneider EL, Mitsui Y. The relationship between in vitro cellular aging and in vivo human age. Proc Natl Acad Sci USA 1972; 73: 3584–3588.CrossRefGoogle Scholar
  10. 10.
    Martin GM. Genetic syndromes in man with potential relevance to the pathobiology of aging. Birth Defects 1978; 14: 5–39.PubMedGoogle Scholar
  11. 11.
    Hoehn H, Bryant EM, Au K, et al. Variegated translocation mosaicism in human fibroblast cultures. Cytogenet Cell Genet 1975; 15: 282–298.PubMedCrossRefGoogle Scholar
  12. 12.
    Epstein CJ, Martin GM, Schultz AL, et al. Werner’s syndrome: a review of its symptomology, natural history, pathology features, genetics and relationship to the natural aging process. Medicine 1966; 45: 177–221.PubMedGoogle Scholar
  13. 13.
    Martin GM, Sprague CA. Life histories of hyperplastoid cell lines from aorta and skin. Exp Mol Pathol 1973; 18: 125–141.PubMedCrossRefGoogle Scholar
  14. 14.
    Rothfels FH, Kupelweiser EB, Parker RC. Effects of X-irradiated feeder layers on mitotic activity and development of aneuploidy in mouse embryo cells in vitro. Can Cancer Conf 1963; 5: 191–223.PubMedGoogle Scholar
  15. 15.
    Weinberg RA. A molecular basis of cancer. Sci Am 1983; 249: 126–143.PubMedCrossRefGoogle Scholar
  16. 16.
    Varmus HE. The molecular genetics of cellular oncogenes. Annu Rev Genet 1984; 18: 553–612.PubMedCrossRefGoogle Scholar
  17. 17.
    Bister K, Jensen HW. Oncogenes in retroviruses and cells: biochemistry and molecular genetics. Adv Cancer Res 1986; 47: 99–188.PubMedCrossRefGoogle Scholar
  18. 18.
    Thrasher JD, Greulich RC. The duodenal progenitor population, I: age related increase in the duration of the cryptal progenitor cycle. J Exp Zool 1965; 159: 39–46.PubMedCrossRefGoogle Scholar
  19. 19.
    Daniel CW. Cell longevity in vivo. In: Finch CE, Hayflick L, eds. Handbook of the Biology of Aging. 1st ed. New York, NY: Van Nostrand Reinhold Co; 1977: 122–158.Google Scholar
  20. 20.
    Harrison DE. Cell and tissue transplantation: a means of studying the aging process. In: Finch CE, Schneider EL, eds. Handbook of the Biology of Aging. 2nd ed. New York, NY: Van Nostrand Reinhold Co; 1985:322356.Google Scholar
  21. 21.
    Norwood TH, Smith JR. The cultured fibroblast-like cell as a model for the study of aging. In: Finch CE, Schneider EL, eds. Handbook of the Biology of Aging. 2nd ed. New York, NY: Van Nostrand Reinhold Co; 1985: 291–321.Google Scholar
  22. 22.
    Cristofalo, VJ, Stanulis-Praeger BM. Cellular senescence in vitro. In: Maramotosch K, ed. Advances in Tissue Culture. Orlando, Fla: Academic Press Inc; 1982; 2: 1–68.Google Scholar
  23. 23.
    Martin GM. Cellular aging-clonal senescence. Am J Pathol 1977; 89: 484–510.PubMedGoogle Scholar
  24. 24.
    Hornsby PJ, Hancock JP, Vo TP, et al. Loss of expression of a differentiated function give steroid 17ahydroxylase, as adrenocortical cells senesce in culture. Proc Natl Acad Sci USA 1987; 84: 1580–1584.PubMedCrossRefGoogle Scholar
  25. 25.
    Martin GM. Proliferative homeostasis and its age-related aberrations. Mech Ageing Del) 1979; 9: 385–391.CrossRefGoogle Scholar
  26. 26.
    Takehara K, LeRoy EC, Grotendorst GR. TGF-ß inhibition of endothelial cell proliferation: alteration of EGF binding and EGF-induced growth-regulatory (competence) gene expression. Cell 1987; 49: 415–422.PubMedCrossRefGoogle Scholar
  27. 27.
    Eaglstein WH. Wound healing and aging. Dermatol Clin 1986; 4: 481–484.PubMedGoogle Scholar
  28. 28.
    Siskind GW. Aging and the immune system. In: Warner HR, Butler RN, Sprott RL, et al, eds. Modern Biological Theories of Aging. New York, NY: Raven Press; 1987: 235–242.Google Scholar
  29. 29.
    Hefton JM, Darlington GJ, Casazza BA, et al. Immunologic studies of aging, V: impaired proliferation of PHA responsive human lymphocytes in culture. J Immunol 1980; 125: 1007–1010.PubMedGoogle Scholar
  30. 30.
    Tice RR, Schneider EL, Kram D, et al. Cytokinetic analysis of the impaired proliferative response of peripheral lymphocytes from aged humans to phytohemagglutinin J Exp Med 1979; 149: 1029–1041.PubMedCrossRefGoogle Scholar
  31. 31.
    Ebbesen P. Aging increases susceptibility of mouse skin to DMBA carcinogenesis independent of general immune status. Science 1974; 183: 217–218.PubMedCrossRefGoogle Scholar
  32. 32.
    Gown AM, Norwood TH. Atherosclerosis and cellular aging. In: Blumenthal HT, ed. Handbook of Disease of Aging. New York, NY: Van Nostrand Reinhold Co; 1983: 149–180.Google Scholar
  33. 33.
    Ross R. The pathogenesis of atherosclerosis-an update. N Engl J Med 1986; 314: 488–500.PubMedCrossRefGoogle Scholar
  34. 34.
    Hayflick L. The cellular basis for biological aging. In: Hayflick L, Finch CE, eds. The Handbook of the Biology of Aging. 1st ed. New York, NY: Van Nostrand Reinhold Co; 1977: 159–186.Google Scholar
  35. 35.
    Kay MMB. Aging of cell membrane molecules leads to appearance of an aging antigen and removal of senescent cells. Gerontology 1985; 31: 215–235.PubMedCrossRefGoogle Scholar
  36. 36.
    Martin GM. Cellular aging-postreplicative cells. Am J Pathol 1977; 89: 513–530.PubMedGoogle Scholar
  37. 37.
    Terry RD, Hansen LA. Some morphometric aspects of Alzheimer disease and of normal aging. In Terry RD, ed. Aging and the Brain. New York, NY: Raven Press; 1988: 109–114.Google Scholar
  38. 38.
    Brody H. Organization of the cerebral cortex, III: a study of aging in the human cerebral cortex. J Comp Neurol 1955; 102: 551–556.CrossRefGoogle Scholar
  39. 39.
    Johnson HA, Erner S. Neuron survival in the aging mouse. Exp Gerontol 1972; 7: 111–117.PubMedCrossRefGoogle Scholar
  40. 40.
    Morgan DG, May PC, Finch CE. Dopamine and serotonin systems in human and rodent brain: effects of age and neurodegenerative disease. J Am Geriatr Soc 1987; 35: 334–345.PubMedGoogle Scholar
  41. 41.
    Sulkin NM, Sulkin DF. Age differences in response to chronic hypoxia in the fine structure of cardiac muscle and autonomic ganglion cells. J Gerontol 1967; 22: 485501.Google Scholar
  42. 42.
    Chen JC, Warshaw JB, Sanadi DR. Regulations of mitochondrial respiration in senescence. J Cell Physiol 1972; 80: 141–148.PubMedCrossRefGoogle Scholar
  43. 43.
    Katz ML, Robison WG Jr. Nutritional influences on auto-oxidation, lipofuscin accumulation, and aging. In: Johnson JE Jr, Walford R, Harman D, et al, eds. Free Radicals, Aging, and Degenerative Diseases. New York, NY: Alan R Liss Inc; 1986: 221–259.Google Scholar
  44. 44.
    Schneider EL. Theories of aging: a perspective. In: Warner HL, Butler RN, Sprott RL, et al, eds. Modern Biological Theories of Aging. New York, NY: Raven Press; 1987: 1–4.Google Scholar
  45. 45.
    Harman D. Free radical theory of aging: role of free radicals in the origination and evolution of life, aging, and disease processes. In: Johnson JE, Walford R, Harman D, et al, eds. Free Radicals, Aging, and Degenerative Diseases. New York, NY: Alan R Liss Inc; 1986: 3–49.Google Scholar
  46. 46.
    Martin GM. Genetic and evolutionary aspects of aging. FASEB J 1979; 38: 1962–1967.Google Scholar
  47. 47.
    Hart RW, Setlow RB. Correlation between deoxyribonucleic acid excision repair and lifespan in a number of mammalian species. Proc Natl Acad Sci USA 1974; 71: 2169–2173.PubMedCrossRefGoogle Scholar
  48. 48.
    Cutler RG. Peroxide-producing potential of tissues: inverse correlation with longevity of mammalian species. Proc Natl Acad Sci USA 1985; 82: 4798–4802.PubMedCrossRefGoogle Scholar
  49. 49.
    Wilson VL, Jones PA. DNA methylation decreases in aging but not in immortal cells. Science 1983; 220: 1055 1057.Google Scholar
  50. 50.
    Mays-Loope L, Chao W, Butcher HC, et al. Decreased methylation of the major mouse interspersed repeated DNA during and in myeloma cells. Dev Genet 1986; 7: 6573.Google Scholar
  51. 51.
    Bierman EL. The effect of donor age in the in vitro lifespan of cultured human arterial smooth-muscle cells. In Vitro 1978; 14: 951–955.PubMedCrossRefGoogle Scholar
  52. 52.
    Glassberg MK, Bern MM, Coughlin SR, et al. Cultured endothelial cells derived from the human iliac arteries. In Vitro 1982; 18: 859–866.PubMedCrossRefGoogle Scholar
  53. 53.
    Rheinwald JO, Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell 1975; 6: 331–344.PubMedCrossRefGoogle Scholar
  54. 54.
    Walford RL, Jawaid SQ, Nalim F. Evidence for in vitro senescence of T lymphocytes cultured from normal human peripheral blood. Age 1981; 4: 67–70.CrossRefGoogle Scholar
  55. 55.
    Rothstein M. Evidence for and against the error catastrophe hypothesis. In: Warner HR, Butler RN, Sprott RL, et al, eds. Modern Biological Theories of Aging. New York, NY: Raven Press; 1987: 139–154.Google Scholar
  56. 56.
    Setlow RB. Theory presentation and background summary. In: Warner HR, Butler RN, Sprott RL, et al, eds. Modern Biological Theories of Aging. New York, NY: Raven Press; 1987: 177–182.Google Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Thomas H. Norwood

There are no affiliations available

Personalised recommendations