Aging embryos
Senescence is a component of normal embryo development
LifeSciencesToday based on the materials of Centro de Regulacion Genomica:
CRG researchers describe that senescence is a normal process in the embryo, and is not only linked to aging and cancerThe results of two studies published in the journal Cell radically change our ideas about senescence (Latin senesco – aging):
Storer et al., Senescence Is a Developmental Mechanism that Contributes to Embryonic Growth and Patterning; Munoz-Espin et al., Programmed Cell Senescence during Mammalian Embryonic Development.
Their authors assign a completely new and unexpected role to senescence, previously associated only with pathological conditions, in particular, with aging and cancer, and provide convincing evidence that this phenomenon is a normal and very important process of the period of embryogenesis. Scientists from the Center for Genomic Regulation (Centro de Regulacion Genomica, CRG), Barcelona, made this discovery together with their colleagues from the National Cancer Research Center (Centro Nacional de Investigaciones Oncologicas, CNIO), Madrid.
Senescence is a condition by which cells restrict proliferation in response to stress. Historically, it has been described in aging and cancer. Spanish scientists have refuted the views on senescence as a phenomenon associated only with stress and proliferation of tumor cells. In their opinion, it plays an important and unique role in the normal development of the embryo.
Senescence is a form of cell cycle arrest associated with tumor suppression and aging. The nature of this phenomenon remains a matter of debate. It has not been recorded in non–pathological conditions, but Spanish scientists describe senescence as a mechanism of normal development acting throughout the embryo, including the apical ectodermal crest and the neural plate - two signaling centers of embryonic structuring. Aging cells of the embryo do not proliferate and have common features with cells in a state of oncogene-induced senescence, including expression levels of p21, p15 and SASP mediators (senescence-associated secretory phenotype). Scientists believe that senescence is a normal programmed mechanism that plays an instructive role in development, and that oncogen-induced senescence is an evolutionarily adapted reactivation of the development process. (Fig. Cell)"Our research has shown for the first time that senescence is a programmed mechanism of development.
This new definition helps us understand its role and significance as a normal process," explains Dr. Bill Keyes, head of the CRG Cancer and Aging Mechanisms Laboratory. "Our work shows that in the embryo, cells in a state of senescence are necessary and their normal secretory function instructs the growth and structuring of tissues."
Dr. Keyes and his colleagues describe senescence as an important part of the biology of the two main signaling centers of the embryo, providing control over the normal development of the limbs and nervous system. Similarly, Manuel Serrano and Daniel Munoz-Espin from CNIO have identified identical processes in two other tissues - in the developing kidneys and ear.
Senescence suppresses the proliferation of damaged cells and has always been associated with cancer and aging. However, Spanish scientists have proved that senescence also occurs during the embryonic development of mammals in many tissues of the embryo, including the mesonephros and the endolymphatic sac of the inner ear. Mechanistically, the senescence in both of these structures is tightly controlled by p21, regulated by the TGF-beta/SMAD and PI3K/FOXO pathways, and does not depend on DNA damage, p53 and other cell cycle inhibitors. Programmed senescence of development (developmentally programmed senescence) is accompanied by infiltration by macrophages, removal of aging cells and tissue remodeling. The loss of senescence caused by the absence of p21 is partially compensated by apoptosis, but still leads to developmental anomalies. Scientists have concluded that the role of programmed senescence of development is to stimulate tissue remodeling, and suggest that from an evolutionary point of view, it is a precursor of damage-induced senescence. (Fig. Cell)In addition, both studies have shown how the coordinated removal of aging cells by macrophages plays a key role in the remodeling of developing tissues – a process necessary for the normal formation of embryo structures.
Interestingly, tissues with a pronounced senescence phenomenon are among those in which congenital anomalies develop most often, and, therefore, the study of the mechanisms regulating senescence in the embryo can help explain the causes of some of these anomalies.
Based on these new data, scientists suggest that senescence associated with aging and cancer is an evolutionary adaptation of one of the mechanisms of development.
"I hope that the discovery of the phenomenon of senescence in a normally developing embryo will allow us to identify new mediators and biomarkers of this condition," says Mekayla Storer, a PhD student at CRG and the first author of the paper. "These findings change our previous understanding of senescence and provide important new information that can be used in the fight against cancer and aging."
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