Sep 23, 2021

8 min read

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