A new development in senescence

Abstract

Cellular senescence is implicated in several pathological responses in the adult, with important repercussions in tumor suppression, wound healing, and aging. Two studies by Muñoz-Espín et al. and Storer et al. now reveal that senescence contributes to embryonic development, suggesting a primordial role in normal physiology.

Figure 1. Main Features of Senescence in the Adult and in the Embryo

Whereas the first is induced by stress, such as telomere uncapping, oncogenic signals, or DNA damage, the second is induced by still undetermined developmental cues. Both programs share a set of features such as senescence-associated β-galactosidase activity (SAβG), senescence-associated heterochromatic foci (SAHF), and some of the members of the senescence-associated secretory phenotype (SASP) such as TGFβ, Wnt, and IGFBP family ligands. Nevertheless, differences exist. Developmental senescence does not depend on the activation of DNA damage response, p53-21, or p16 tumor suppressor pathways and does not present some of the SASP-related factors such as IL8 (Cxcl1, 2, and 5 homologs in mice) and IL6. Although additional regulators may exist, senescence in the embryo is mainly mediated by p21 and regulated by the TGFβ/SMAD- and FOXO/PI3K-signaling pathways. Tissue remodeling is a main consequence of both programs. By recruiting the immune system, senescence mediates the elimination of unwanted/transient cells or structures. Developmental senescence may additionally dictate the balance between cell populations or instruct developmental processes.