TY - JOUR
T1 - To clear, or not to clear (senescent cells)? That is the question
AU - Lujambio, Amaia
N1 - Publisher Copyright:
© 2016 The Authors. BioEssays published by WILEY Periodicals, Inc.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Cellular senescence is an anti-proliferative program that restricts the propagation of cells subjected to different kinds of stress. Cellular senescence was initially described as a cell-autonomous tumor suppressor mechanism that triggers an irreversible cell cycle arrest that prevents the proliferation of damaged cells at risk of neoplastic transformation. However, discoveries during the last decade have established that senescent cells can also impact the surrounding tissue microenvironment and the neighboring cells in a non-cell-autonomous manner. These non-cell-autonomous activities are, in part, mediated by the selective secretion of extracellular matrix degrading enzymes, cytokines, chemokines and immune modulators, which collectively constitute the senescence-associated secretory phenotype. One of the key functions of the senescence-associated secretory phenotype is to attract immune cells, which in turn can orchestrate the elimination of senescent cells. Interestingly, the clearance of senescent cells seems to be critical to dictate the net effects of cellular senescence. As a general rule, the successful elimination of senescent cells takes place in processes that are considered beneficial, such as tumor suppression, tissue remodeling and embryonic development, while the chronic accumulation of senescent cells leads to more detrimental consequences, namely, cancer and aging. Nevertheless, exceptions to this rule may exist. Now that cellular senescence is in the spotlight for both anti-cancer and anti-aging therapies, understanding the precise underpinnings of senescent cell removal will be essential to exploit cellular senescence to its full potential.
AB - Cellular senescence is an anti-proliferative program that restricts the propagation of cells subjected to different kinds of stress. Cellular senescence was initially described as a cell-autonomous tumor suppressor mechanism that triggers an irreversible cell cycle arrest that prevents the proliferation of damaged cells at risk of neoplastic transformation. However, discoveries during the last decade have established that senescent cells can also impact the surrounding tissue microenvironment and the neighboring cells in a non-cell-autonomous manner. These non-cell-autonomous activities are, in part, mediated by the selective secretion of extracellular matrix degrading enzymes, cytokines, chemokines and immune modulators, which collectively constitute the senescence-associated secretory phenotype. One of the key functions of the senescence-associated secretory phenotype is to attract immune cells, which in turn can orchestrate the elimination of senescent cells. Interestingly, the clearance of senescent cells seems to be critical to dictate the net effects of cellular senescence. As a general rule, the successful elimination of senescent cells takes place in processes that are considered beneficial, such as tumor suppression, tissue remodeling and embryonic development, while the chronic accumulation of senescent cells leads to more detrimental consequences, namely, cancer and aging. Nevertheless, exceptions to this rule may exist. Now that cellular senescence is in the spotlight for both anti-cancer and anti-aging therapies, understanding the precise underpinnings of senescent cell removal will be essential to exploit cellular senescence to its full potential.
KW - SASP
KW - cancer
KW - immune surveillance
KW - senescence
UR - http://www.scopus.com/inward/record.url?scp=84978823961&partnerID=8YFLogxK
U2 - 10.1002/bies.201670910
DO - 10.1002/bies.201670910
M3 - Review article
C2 - 27417123
AN - SCOPUS:84978823961
SN - 0265-9247
VL - 38
SP - S56-S64
JO - BioEssays
JF - BioEssays
ER -