On the Origins of Cellular Senescence

Construction worker analogy for the end replication problem.
Timeline of important discoveries on the road to understanding replicative senescence (1940–1998).
  1. Carrel, A. & Ebeling, A. H. Age and multiplication of fibroblasts . J. Exp. Med. 34, 599– 606 (1921). doi: 10.1084/jem.34.6.599
  2. Hayflick, L., & Moorhead, P. S. (1961). The serial cultivation of human diploid cell strains. Experimental cell research, 25(3), 585–621. doi: 10.1016/0014–4827(61)90192–6
  3. Hayflick, Leonard. “Mortality and immortality at the cellular level. A review.” Biochemistry-New York-English Translation of Biokhimiya 62.11 (1997): 1180–1190. PMID: 9467840
  4. Wright, W. E., & Hayflick, L. (1975). Nuclear control of cellular aging demonstrated by hybridization of anucleate and whole cultured normal human fibroblasts. Experimental cell research, 96(1), 113–121. doi: 10.1016/s0014–4827(75)80043–7
  5. Olovnikov A. M. (1971). Printsip marginotomii v matrichnom sinteze polinukleotidov [Principle of marginotomy in template synthesis of polynucleotides]. Doklady Akademii nauk SSSR, 201(6), 1496–1499. ResearchGate Article
  6. Blackburn, E. H., & Gall, J. G. (1978). A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. Journal of molecular biology, 120(1), 33–53. doi: 10.1016/0022–2836(78)90294–2
  7. Greider, C. W., & Blackburn, E. H. (1985). Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. cell, 43(2), 405–413. doi: 10.1016/0092–8674(85)90170–9
  8. Harley, C. B., Futcher, A. B., & Greider, C. W. (1990). Telomeres shorten during ageing of human fibroblasts. Nature, 345(6274), 458–460. doi: 10.1038/345458a0
  9. Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C. P., Morin, G. B., … & Wright, W. E. (1998). Extension of life-span by introduction of telomerase into normal human cells. science, 279(5349), 349–352. doi: 10.1126/science.279.5349.349



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