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Can we differentiate between beneficial and detrimental senescent cells?

Image credit: https://www.nature.com/articles/s41570-019-0108-0?platform=oscar&draft=collection

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Shubhankar Kulkarni
Shubhankar Kulkarni Aug 04, 2020
Senescence is not always detrimental to human health. During embryonic development, programmed senescence eliminates senescent cells and reshapes tissues, and loss of senescence at this stage leads to developmental abnormalities. Senescence also improves glucose homeostasis and tissue repair and regeneration and elimination of senescent cells hampers these processes. Even optimum exposure to senescence-associated secretory phenotype was shown to initiate pro-regenerative stemness (cellular plasticity) in mouse keratinocytes.

Therefore, is there a difference between beneficial and detrimental senescent cells or is it completely context-dependent?

[1]Muñoz-Espín D, Cañamero M, Maraver A, Gómez-López G, Contreras J, Murillo-Cuesta S, et al. Programmed Cell Senescence during Mammalian Embryonic Development. Cell [Internet]. 2013 Nov;155(5):1104–18. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0092867413012956

[2]Storer M, Mas A, Robert-Moreno A, Pecoraro M, Ortells MC, Di Giacomo V, et al. Senescence Is a Developmental Mechanism that Contributes to Embryonic Growth and Patterning. Cell [Internet]. 2013 Nov;155(5):1119–30. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0092867413013597

[3]Helman A, Klochendler A, Azazmeh N, Gabai Y, Horwitz E, Anzi S, et al. p16Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion. Nat Med [Internet]. 2016 Apr 7;22(4):412–20. Available from: http://www.nature.com/articles/nm.4054

[4]Demaria M, Ohtani N, Youssef SA, Rodier F, Toussaint W, Mitchell JR, et al. An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA. Dev Cell [Internet]. 2014 Dec;31(6):722–33. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1534580714007291

[5]Ritschka B, Storer M, Mas A, Heinzmann F, Ortells MC, Morton JP, et al. The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. Genes Dev [Internet]. 2017 Jan 15;31(2):172–83. Available from: http://genesdev.cshlp.org/lookup/doi/10.1101/gad.290635.116

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Jamila
Jamila Aug 10, 2020
When senescent cells have targeted specific cells and completed their job (tissue remodelling, embryonic development, etc) the immune cells easily remove them; this is termed as acute senescence. However, prolonged cellular stress can induce chronic senescence, and that’s where the issues begin. In chronic senescence, specific cell types are not targeted and the senescent cells are not cleared away efficiently. It is already known that the immune system function deteriorates with age; therefore, the immune cells may not be able to cope with the accumulation of senescent cells. Furthermore, the ability of immune cells to clear the senescent cells may depend on SASP.(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214092/) It does seem that there are differences between early-stage and late-stage senescent cells. Acute senescence is a tightly controlled process, whereas, chronic senescence is highly dysregulated. The differences between early and late-stage senescent cells should be further explored. It seems that a combination of these chronic senescent cells (late-stage) and the conditions may promote the negative effects of cellular senescence and thus accelerate aging.

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