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cellular (relicative) senescence; senescent cell; zombie cell

- In vitro: - cessation of proliferation by multiple subcultures of cultured cells - In vivo: - presumptive process constrained by structural properties of organs & tissues & paracrine & endocrine influence of other constituents of the organism Pathology: Characterized by: 1) cessation of mitosis 2) telomere shortening 3) tumor promoter-like activity - enhancement of neoplastic transformation of proneoplastic cells in vivo 4) expression of biomarkers for cellular senescence - p16ink4a [2] - urokinase plasminogen activator surface receptor (uPAR) [12] 5) resistance to apoptosis 6) senescent cells identified as excitatory neurons expressing CDKN2D contain 1.8-fold larger nuclei, more lipofuscin than CDKN2D-negative neurons & overlap with neurons containing neurofibrillary tangles in brains of patients with Alzheimer's disease [10] 7) allegedly produce proinflammatory substances [6,11] 8) allegedly old cells with irreversibly damaged DNA [11] Notes: - senescent cells may play a role in wound healing [6] - removal of senescent cells in young animals inhibits wound healing in young animals, but improves wound healing in old animals [6] - in vivo vs in vitro, type of animal, type of cell not specified - cellular senescence aligns with the antagonistic pleiotropy theory of aging - benefit for tumor suppression early in life might lead to deleterious effects later in life [9] - see biology of aging for theories of aging - accumulation of p16ink4a* in senescent cells may disrupt tissue structure & function & contribute to age-related pathology [2] - clearance of p16ink4a-containing cells may prevent &/or attenuate age-related degenerative] pathology [2] - clearance of cell surface uPAR-containing cells with CAR T-cell therapy may prevent &/or attenuate age-related degenerative pathology [12] * p16ink4a is a marker of cells that have left the cell cycle; widely expressed, but not detected in brain or skeletal muscle

Related

circulating plasma factors in cellular senescence

General

senescence

Database Correlations

OMIM 116960

References

  1. Eugenia Wang, University of Louisville, in: Microarray Technology and Aging Workshop, March 14, 2003
  2. Baker DJ et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 2011 Nov 10; 479:232 PMID: 22048312 - Peeper DS. Old cells under attack. Nature 2011 Nov 10; 479:186 PMID: 22071762
  3. Yamazaki Y, Baker DJ, Tachibana M et al Vascular Cell Senescence Contributes to Blood-Brain Barrier Breakdown. Stroke. 2016 Feb 16. PMID: 26883501
  4. Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005 Feb 25;120(4):513-22. Review. PMID: 15734683 Free Article
  5. Giaimo S, d'Adda di Fagagna F. Is cellular senescence an example of antagonistic pleiotropy? Aging Cell. 2012 Jun;11(3):378-83. Review. PMID: 22329645 Free Article
  6. Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016 - Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  7. Munoz-Espin D, Serrano M. Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol. 2014 Jul;15(7):482-96. Review. PMID: 24954210
  8. Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest. 2013 Mar;123(3):966-72. Review. PMID: 23454759 Free PMC Article
  9. van Deursen JM. The role of senescent cells in ageing. Nature. 2014 May 22;509(7501):439-46. Review. PMID: 24848057 Free PMC Article
  10. Dehkordi SK, Walker J, Sah E et al. Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology. Nat Aging 2021 https://www.nature.com/articles/s43587-021-00142-3
  11. Wajngarten M Is There Hope in the Fight Against Aging? Medscape. December 19, 2022 https://www.medscape.com/viewarticle/985809
  12. Amor C, Fernandez-Maestre I, Chowdhury S et al Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction. Nat Aging. 2024 Jan 24. PMID: 38267706 https://www.nature.com/articles/s43587-023-00560-5