Developing senescence to remodel the embryo

Abstract

Cellular senescence is an irreversible form of cell cycle arrest that has been linked to several pathological conditions. In particular, senescence can function as a tumor suppressor mechanism, but is also thought to contribute to organismal aging. Paradoxically however, through the secretion of various factors, collectively termed the senescence-associated secretory phenotype (SASP), senescent cells can also have tumor-promoting and tissue-remodeling functions. In addition, senescent cells can play beneficial roles in tissue repair and wound healing, and reconciling these contradictory features from an evolutionary standpoint has been challenging. Moreover, senescent cells had not previously been documented in non-pathological conditions. Recently however, 2 studies have identified cellular senescence as a programmed mechanism that contributes to tissue patterning and remodeling during normal embryonic development. These findings have significant implications for our understanding of cellular senescence and help to clarify the paradoxes and the evolutionary origin of this process.

Keywords: aging; embryo; evolution; senescence; tumour suppression.

Figure 1.

Schematic outline of different types of senescence, and their effect on tissue growth. Replicative senescence and tissue aging are mediated largely by p16-driven senescence, which likely contributes to growth suppression in the aged state. Developmental senescence is mediated largely by p21, likely acts in a growth-promoting manner, leading to tissue patterning, cell-fate instruction and remodeling. While oncogene-induced senescence probably combines aspects of both, having tumor/growth suppressive functions as well as growth promoting effects mediated by the SASP.