The Senescent Cell, SC

  • Bernard Swynghedauw
Part of the Practical Issues in Geriatrics book series (PIG)


The senescent cells and their soluble (inflammatory factors, proteolytic components) or insoluble (miRs) secretomes are at the heart of most of the clinical manifestations of senescence, including fibrosis.


Senescent cell Secretome Stem cell Progenitor cells miR Fibrosis 


  1. 1.
    Baker DJ, et al. Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature. 2016;530:184–9.CrossRefGoogle Scholar
  2. 2.
    Brondello JM, et al. La sénescence cellulaire. Un nouveau mythe de Janus. Méd/Sci. 2012;28:288–94.Google Scholar
  3. 3.
    Campisi J, et al. Ageing, cellular senescence, and cancer. Annu Rev Physiol. 2013;75:685–705.CrossRefGoogle Scholar
  4. 4.
    Childs BG, et al. Cellular senescence in ageing and age-related disease: from mechanisms to theory. Nat Med. 2015;21:1424–35.CrossRefGoogle Scholar
  5. 5.
    Chung HY, et al. Molecular inflammation : underpinnings of ageing and age-related diseases. Ageing Res Rev. 2009;8:18–30.CrossRefGoogle Scholar
  6. 6.
    Deursen van JM. The role of senescent cells in ageing. Nature. 2014;509:439–46.CrossRefGoogle Scholar
  7. 7.
    Jeon OH, et al. Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nat Med. 2017;23:775–82.CrossRefGoogle Scholar
  8. 8.
    Jurk D, et al. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Nature Commun. 2014;5:4172. Scholar
  9. 9.
    Kirkland JL, et al. Cellular senescence: a translational perspective. EBioMedicine. 2017;21:21–8.CrossRefGoogle Scholar
  10. 10.
    Malaquin N. Keeping the senescence secretome under control : molecular reins on the senescence-associated secretory phenotype. Exp Gerontol. 2016;82:39–49.CrossRefGoogle Scholar
  11. 11.
    Sturmlechner I, et al. Cellular senescence in renal ageing and disease. Nat Rev Nephrol. 2017;13:77–89.CrossRefGoogle Scholar
  12. 12.
    Weilner S, et al. Secretion of microvesicular miRNAs in cellular and organismal ageing and age-related diseases. Exp Gerontol. 2013;48:626–33.CrossRefGoogle Scholar
  13. 13.
    Rodier F, et al. Four faces of cellular senescence. J Cell Biol. 2011;192:547–56.CrossRefGoogle Scholar
  14. 14.
    Childs BG, et al. Senescent cells: an emerging target for diseases of ageing. Nat Rev Drug Discov. 2017;16:718–35.CrossRefGoogle Scholar
  15. 15.
    Hayflick L, et al. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961;25:585–621.CrossRefGoogle Scholar
  16. 16.
    Jeyapalan JC, et al. Accumulation of senescent cells in mitotic tissues of ageing primates. Mech Ageing Dev. 2007;128:36–44.CrossRefGoogle Scholar
  17. 17.
    Ronaldson-Bouchards K, et al. Advanced maturation of human cardiac tissue grown from pluripotent stem cells. Nature. 2018;556:239–43.CrossRefGoogle Scholar
  18. 18.
    Schultz MB, et al. When stem cells grow old: phenotypes and mechanisms of stem cells ageing. Development. 2016;143:3–14.CrossRefGoogle Scholar
  19. 19.
    Wells JM, et al. Diverse mechanisms for endogenous regeneration and repair in mammalian organs. Nature. 2018;557:322–8.CrossRefGoogle Scholar
  20. 20.
    Panda A, et al. Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol. 2009;30:325–33.CrossRefGoogle Scholar
  21. 21.
    Hirschfeld HP, et al. Osteosarcopenia: where bone, muscle and fat collide. Osteoporos Int. 2017;28(10):2781–90. Scholar
  22. 22.
    Tchkonia T, et al. Cellular senescence and the senescent phenotype: therapeutic opportunities. J Clin Invest. 2013;123:966–72.CrossRefGoogle Scholar
  23. 23.
    Sone H, et al. Pancreatic beat cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice. Diabetologia. 2005;48:58–67.CrossRefGoogle Scholar
  24. 24.
    Zhang G, et al. Hypothalamic programming of systemic ageing involving IKK-beta, NF-kappaB and GnRH. Nature. 2013;497:211–6.CrossRefGoogle Scholar
  25. 25.
    Zhang Y, et al. Hypothalamic stem cells control ageing speed partly through exosomal miRNAs. Nature. 2017;548:52–7.CrossRefGoogle Scholar
  26. 26.
    Bussian TJ, et al. Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Nature. 2018;562:578–82.CrossRefGoogle Scholar
  27. 27.
    Bartling B. Cellular senescence in normal and premature lung ageing. Z Gerontol Geriat. 2013;46:613–22.CrossRefGoogle Scholar
  28. 28.
    Ogrodnik M, et al. Cellular senescence drives age-dependent hepatic steatosis. Nat Commun. 2017;8:15691. Scholar
  29. 29.
    Waldenström A, et al. Role of the exosomes in myocardial remodeling. Circ Res. 2014;114:315–24.CrossRefGoogle Scholar
  30. 30.
    Olivieri F, et al. Circulating inflamma-miR in ageing and age-related diseases. Front Genet. 2013;4:1–9.CrossRefGoogle Scholar
  31. 31.
    Menni C, et al. Circulating proteomic signatures of chronological ages. J Gerontol A Biol. 2015;70:809–16.CrossRefGoogle Scholar
  32. 32.
    Pedersen BK, et al. Muscles, exercise and obesity : skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012;8:457–65.CrossRefGoogle Scholar
  33. 33.
    Naylor RM, et al. Senescent cells : a novel therapeutic target for ageing and age-related diseases. Clin Pharmacol Ther. 2013;93:105–16.CrossRefGoogle Scholar
  34. 34.
    Weber KT. Wound healing in cardiovascular disease. Armonk: Futura Publishing Company; 1995.Google Scholar
  35. 35.
    Hashimoto M, et al. Elimination of p19ARF-expressing cells enhances pulmonary function in mice. JCI Insight. 2016;1:e87732.CrossRefGoogle Scholar
  36. 36.
    Rockey DC, et al. Fibrosis – A common pathway to injury and failure. N Engl J Med. 2015;372:1138–49.CrossRefGoogle Scholar
  37. 37.
    Schafer MJ, et al. Cellular senescence mediates fibrotic pulmonary disease. Nat Commun. 2017;8:1–11.CrossRefGoogle Scholar
  38. 38.
    Weber KT, et al. Myofibroblasts-mediated mechanisms of pathological remodeling of the heart. Nat Rev Cardiol. 2013;10:15–26.CrossRefGoogle Scholar
  39. 39.
    Elred JA, et al. The lense as a model for fibrotic disease. Philos Trans R Soc Lond B Biol Sci. 2011;366:1301–19.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Bernard Swynghedauw
    • 1
  1. 1.French Institute of Health and Medical ResearchParisFrance

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