The senescence-associated secretory phenotype and its regulation

Lopes-Paciência, Stéphane; Saint-Germain, Emmanuelle; Rowell, Marie-Camille; Ruiz, Ana Fernández; Kalegari, Paloma; Ferbeyre, Gerardo

doi:10.1016/j.cyto.2019.01.013

Cited by 360 publications

(301 citation statements)

References 130 publications

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“…Alongside cytokines and grow factors, several extracellular enzymes and associated proteins are part of the SASP. The most representative groups involved are matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and serine proteases [67] (Fig. 3).…”

Section: How Are Senescent Cells?mentioning

confidence: 99%

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review

et al. 2020

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Life expectancy has increased substantially over the last few decades, leading to a worldwide increase in the prevalence and burden of agingassociated diseases. Recent evidence has proven that cellular senescence contributes substantially to the development of these disorders. Cellular senescence is a state of cell cycle arrest with suppressed apoptosis and concomitant secretion of multiple bioactive factors (the senescence-associated secretory phenotype-SASP) that plays a physiological role in embryonic development and healing processes. However, DNA damage and oxidative stress that occur during aging cause the accumulation of senescent cells, which through their SASP bring about deleterious effects on multiple organ and systemic functions. Ablation of senescent cells through genetic or pharmacological means leads to improved life span and health span in animal models, and preliminary evidence suggests it may also have a positive impact on human health. Thus, strategies to reduce or eliminate the burden of senescent cells or their products have the potential to impact multiple clinical outcomes with a single intervention. In this review, we touch upon the basics of cell senescence and summarize the current state of development of therapies against cell senescence for human use.

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Section: How Are Senescent Cells?mentioning

confidence: 99%

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review

et al. 2020

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“…The number of senescent cells in tissues increases with age (Spaulding et al, 1997;Krishnamurthy et al, 2004;Herbig et al, 2006;Krizhanovsky et al, 2008;Vidal et al, 2012;Waaijer et al, 2012), and the rate of their accumulation predicts the lifespan of mice (Jurk et al, 2014). The secretions from senescent cells lead to a senescence-associated secretory phenotype (SASP), which might contribute to aging-associated tissue dysfunction or the development of a cancerous niche in old tissue (Coppe et al, 2010;Castro-Vega et al, 2015;Buhl et al, 2019;Lopes-Paciencia et al, 2019). A recent study showed that the transplantation of senescent cells into mice leads to the early onset of aging-related phenotypes (Xu et al, 2017(Xu et al, , 2018, which supports the current hypothesis that senescence can be a driver of aging (Krtolica et al, 2001;Sturmlechner et al, 2017;Lewis-McDougall et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Transient DNMT3L Expression Reinforces Chromatin Surveillance to Halt Senescence Progression in Mouse Embryonic Fibroblast

Hui

Kao

et al. 2020

Front. Cell Dev. Biol.

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“…Identification of oxidative stress as a component of CEnC senescence has prompted investigators to add ascorbic acid as a supplement to early media formulations (added to F99 and M4) to reduce/inhibit oxidant-induced stress/apoptosis (Serbecic and Beutelspacher, 2005; Shima et al, 2011) and to use p38MAPK inhibitors to delay the onset of senescence, but this approach has shown mixed results (Hongo et al, 2017; Nakahara et al, 2018; Sheerin et al, 2012). In addition, senescent CEnC in vitro are characterized by the Senescence-Associated Secretory Phenotype (SASP), which includes the secretion of immune-regulating factors (cytokines, chemokines and growth factors) that have been demonstrated to support tumorigenesis in adjacent epithelial tissues (Georgilis et al, 2018; Laberge et al, 2015; Lau and David, 2019; Lopes-Paciencia et al, 2019). As a remedy to senescence, we identify both classical and novel pathways associated with CEnC senescence that can be manipulated experimentally to potentially achieve significant CEnC expansion with minimal senescence.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion

Frausto¹,

Swamy²,

Peh

et al. 2019

Preprint

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SUMMARYThe advent of cell culture-based methods for the establishment and expansion of human corneal endothelial cells (CEnC) has provided a source of transplantable corneal endothelium, with a significant potential to challenge the one donor-one recipient paradigm. However, concerns over cell identity remain, and a comprehensive characterization of the cultured CEnC across serial passages has not been performed. To this end, we compared two established CEnC culture methods by assessing the transcriptomic changes that occur during in vitro expansion. In confluent monolayers, low mitogenic culture conditions preserved corneal endothelial cell state identity better than culture in high mitogenic conditions. Expansion by continuous passaging induced replicative cell senescence. Transcriptomic analysis of the senescent phenotype identified a cell senescence signature distinct for CEnC. We identified activation of both classic and new cell signaling pathways that may be targeted to prevent senescence, a significant barrier to realizing the potential clinical utility of in vitro expansion.

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The senescence-associated secretory phenotype and its regulation

Cited by 360 publications

References 130 publications

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review

Transient DNMT3L Expression Reinforces Chromatin Surveillance to Halt Senescence Progression in Mouse Embryonic Fibroblast

Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion

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