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Targeting the Senescence-Associated Secretory Phenotype

  • Author / Creator
    Perrott, Kevin M
  • Age is the single-most significant variable in the loss of normal tissue homeostasis resulting in degenerative disease. Increasing with age is a slight, but significant rise in pro-inflammatory factors in the absence of detectable infection, also known as “sterile inflammation”. Although the source(s) of this low-level chronic inflammation remain unclear, senescent cells have emerged as one potential candidate. Cellular senescence is an essentially irreversible growth-arrested state adopted by mitosis-competent cells, usually in response to potentially oncogenic stimuli. Because the main feature of senescence is growth-arrest, senescence has been described as a tumor suppressor mechanism, but the presence of senescent cells in a variety of physiological contexts, including regeneration during wound healing and embryonic development in addition to age-related pathologies, suggests a more complex role. Indeed the presence of senescent cells in multiple settings becomes more interesting when coupled with the recent discovery that they often express a “Senescence-Associated Secretory Phenotype” (SASP), secreting inflammatory factors into the extracellular milieu including many cytokines and proteases. These factors play important roles in normal tissue homeostasis, however, their chronic expression also has the potential to damage tissues and promote carcinogenesis. Senescent cells and their SASP thus have the potential to affect regenerative processes as well as as degenerative conditions, becoming targets for intervention to influence the cellular environment and maintain tissue integrity.This thesis asks the question: Can we identify substances able to decrease the pro-inflammatory nature of the SASP and what impact on the development of cancer can this reduction produce?

  • Subjects / Keywords
  • Graduation date
    Spring 2019
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/r3-vrx2-5p39
  • License
    Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.