In addition to providing a protective role in tumour suppression and tissue damage, senescent cells may also function in embryonic development. It was suggested that cell- cell fusion induced senescence might play a physiological function in the placenta, thereby aiding embryonic development. ERVWE1, a fusion protein involved in the formation of the syncytiotrophoblast of the placenta causes cell fusion and induction of cell senescence in both cancer cells and normal fibroblasts. Fusion induced senescence (FIS) in vitro and in vivo is accompanied by activation of a DDR, p53 and p16(INK4a) dependent pathways. ERVWE1 mediated physiological cell fusion during embryonic development forms the syncytiotrophoblast that serves as the maternal/fetal interface at the placenta. The question of why the senescence program may be useful in normal placental function remains to be answered. However, it can be suggested that the resistance of senescent cells to apoptosis is necessary to maintain the viability of the syncytiotrophoblast. In addition, secretion of proteases, that are normally associated with senescent cells, may function to maintain feto-placental homeostasis. Placental proteases are required for the metabolism of vasoactive and immunomodulating peptides, thereby controlling the exchange of peptide hormones across the placenta and metabolic breakdown of maternal nutrients. Cytokine production is another feature of senescent cells that may play important roles within the placenta. IL-8, one of the main cytokines secreted by senescent cells, is necessary for normal placental function . Cytokine secretion may help regulate placental growth during pregnancy in addition to protecting the foetus from pathological organisms and facilitating interaction with immune cells. Further research is necessary in order to understand the functional significance of the senescence program in the placenta.
A blog for those interested in the physiological and pathological impact of senescent cells.
Showing posts with label placenta. Show all posts
Showing posts with label placenta. Show all posts
Cellular Senescence in Placental Development.
Physiological and pathological consequences of cellular senescence
Abstract
Cellular senescence, a permanent state of cell cycle arrest accompanied by a complex phenotype, is an essential mechanism that limits tumorigenesis and tissue damage. In physiological conditions, senescent cells can be removed by the immune system, facilitating tumor suppression and wound healing. However, as we age, senescent cells accumulate in tissues, either because an aging immune system fails to remove them, the rate of senescent cell formation is elevated, or both. If senescent cells persist in tissues, they have the potential to paradoxically promote pathological conditions. Cellular senescence is associated with an enhanced pro-survival phenotype, which most likely promotes persistence of senescent cells in vivo. This phenotype may have evolved to favor facilitation of a short-term wound healing, followed by the elimination of senescent cells by the immune system. In this review, we provide a perspective on the triggers, mechanisms and physiological as well as pathological consequences of senescent cells.
LINK: Burton and Krizhanovsky (2014) Physiological and pathological consequences of cellular senescence
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