Cellular Senescence in Placental Development.

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.



LINKS:

Cell fusion induced by ERVWE1 or measles virus causes cellular senescence

Physiological and pathological consequences of cellular senescence

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The main focus of ageing research is to prevent/combat age-related disease and disability, allowing everyone to live healthier lives for longer.