TORn about SASP regulation

Herranz, Nicolás; Gallage, Suchira; Gil, Jesús

doi:10.1080/15384101.2015.1105694

Cited by 11 publications

(9 citation statements)

References 7 publications

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Section: Metabolic Changes Detected During Oismentioning

confidence: 99%

“…The SASP has been shown to exert paracrine interactions to modulate the reinforcement and/or propagation of the senescent status (8–10, 89). Some of the key players which are induced by and in turn sustain and propagate the senescence phenotype belong to the family of the interleukins (especially the pro-inflammatory IL6 and IL1, as well as IL8) (8–10, 89, 90). In addition, components of the tumor growth factor (TGF)-β and insulin-like growth factor (IGF)/IGF receptor pathways have shown to play a prominent role in the SASP (8–10, 89, 90).…”

Section: Metabolic Changes Detected During Oismentioning

confidence: 99%

“…Some of the key players which are induced by and in turn sustain and propagate the senescence phenotype belong to the family of the interleukins (especially the pro-inflammatory IL6 and IL1, as well as IL8) (8–10, 89, 90). In addition, components of the tumor growth factor (TGF)-β and insulin-like growth factor (IGF)/IGF receptor pathways have shown to play a prominent role in the SASP (8–10, 89, 90). However, it is important to note that the full composition and effectors of the SASP is strongly influenced by the type of model system used (6).…”

Section: Metabolic Changes Detected During Oismentioning

confidence: 99%

“…At the same time, long-term persisting tumor senescent cells can profoundly alter the microenvironment through SASP-mediated paracrine effects and detrimentally affect neighboring cells (8–10, 88, 89, 113). In fact, it has been shown both in vitro and in vivo that factors from the SASP exacerbate malignant growth and behavior of tumor cells from several malignancies, including breast and prostate cancer as well as melanoma (88).…”

Section: Detection Of Senescence In Vivomentioning

confidence: 99%

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The Immortal Senescence

Bianchi‐Smiraglia

Lipchick

Nikiforov

2016

Methods in Molecular Biology

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Activation of oncogenic signaling paradoxically results in the permanent withdrawal from cell cycle and induction of senescence (oncogene-induced senescence (OIS)). OIS is a fail-safe mechanism used by the cells to prevent uncontrolled tumor-growth and, as such, it is considered as the first barrier against cancer. In order to progress, tumor cells thus need to first overcome the senescent phenotype. Despite the increasing attention gained by OIS in the past 20 years, this field is still rather young due to continuous emergence of novel pathways and processes involved in OIS. Among the many factors contributing to incomplete understanding of OIS are the lack of unequivocal markers for senescence and the complexity of the phenotypes revealed by senescent cells in in vivo and in vitro. OIS has been shown to play major roles at both the cellular and organismal levels in biological processes ranging from embryonic development to barrier to cancer progression. Here we will briefly outline major advances in methodologies that are being utilized for induction, identification and characterization of molecular processes in cells undergoing oncogene-induced senescence. The full description of such methodologies is provided in the corresponding chapters of the Book.

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Section: Metabolic Changes Detected During Oismentioning

confidence: 99%

Section: Metabolic Changes Detected During Oismentioning

confidence: 99%

Section: Metabolic Changes Detected During Oismentioning

confidence: 99%

Section: Detection Of Senescence In Vivomentioning

confidence: 99%

See 2 more Smart Citations

The Immortal Senescence

Bianchi‐Smiraglia

Lipchick

Nikiforov

2016

Methods in Molecular Biology

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“…Additionally, MAPKAPK2 phosphorylates and inhibits the RNA-binding protein ZFP36L1, thereby stabilizing SASP gene targets containing AREs (AU-rich elements). 31 Shifts in intracellular Ca 2+ also play a part in mTOR signaling; 32 conversely, mTOR contributes to age-associated shifts in Ca 2+ mobilization. 33…”

Section: Introductionmentioning

confidence: 99%

Redox and mTOR-dependent regulation of plasma lamellar calcium influx controls the senescence-associated secretory phenotype

Chandrasekaran

Lee

Zhang

et al. 2020

Exp Biol Med (Maywood)

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Cellular senescence has evolved as a protective mechanism to arrest growth of cells with oncogenic potential but is accompanied by the often pathologically deleterious senescence-associated secretory phenotype (SASP). Here we demonstrate an H2O2-dependent functional disruption controlling senescence-associated Ca2+ homeostasis and the SASP. Senescent cells fail to respond to H2O2-dependent plasma lamellar Ca2+ entry when compared to pre-senescent cells. Limiting exposure to senescence-associated H2O2 restores H2O2-dependent Ca2+ entry as well as transient receptor potential cation channel subfamily C member 6 (TRPC6) function. SA-TRPC6 and SASP expression is blocked by restoring Ca2+ entry with the TRP channel antagonist SKF-96365 or by the mTOR inhibitors rapamycin and Ku0063794. Together, our findings provide compelling evidence that redox and mTOR-mediated regulation of Ca2+ entry through TRPC6 modulates SASP gene expression and approaches which preserve normal Ca2+ homeostasis may prove useful in disrupting SASP activity. Impact statement Through its ability to evoke responses from cells in a paracrine fashion, the senescence-associated secretory phenotype (SASP) has been linked to numerous age-associated disease pathologies including tumor invasion, cardiovascular dysfunction, neuroinflammation, osteoarthritis, and renal disease. Strategies which limit the amplitude and duration of SASP serve to delay age-related degenerative decline. Here we demonstrate that the SASP regulation is linked to shifts in intracellular Ca2+ homeostasis and strategies which rescue redox-dependent calcium entry including enzymatic H2O2 scavenging, TRP modulation, or mTOR inhibition block SASP and TRPC6 gene expression. As Ca2+ is indispensable for secretion from both secretory and non-secretory cells, it is exciting to speculate that the expression of plasma lamellar TRP channels critical for the maintenance of intracellular Ca2+ homeostasis may be coordinately regulated with the SASP.

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Genes acting in longevity‐related pathways in the endoparasitoid, Pteromalus puparum

Xiong

et al. 2019

Arch Insect Biochem Physiol

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Among insects, lifespans vary over a broad range, from the short‐lived mayflies to the 17‐year periodical cicadas. Generally, lifespans are determined by a phase in life, the reproductive lifespan, which varies among species. Numerous pathways, such as the insulin/insulin‐like growth factor signaling pathway, the target of rapamycin pathway and the mitogen‐activated protein kinase/extracellular signal‐regulated kinases pathways, influence aging and lifespan. Components of these pathways were identified as lifespan‐related genes, including genes mediating growth, metabolism, development, resistance, and other processes. Many age‐related genes have been discovered in fruit flies, honeybees, and ants among other insect species. Studies of insect aging and longevity can help understand insect biology and develop new pest management technologies. In this paper, we interrogated the new Pteromalus puparum genome, from which we predicted 133 putative lifespan‐related genes based on their homology with known lifespan‐related genes of Drosophila melanogaster. These genes function in five signaling pathways and three physiological processes. The conserved domain structures of these genes were predicted and their expression patterns were analyzed. Amino acid sequence alignments and domain structure analysis indicate that most components remain conserved across at least six insect orders. The data in this paper will facilitate future work on parasitoid lifespans, which may have economic value in biocontrol programs.

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TORn about SASP regulation

Cited by 11 publications

References 7 publications

The Immortal Senescence

The Immortal Senescence

Redox and mTOR-dependent regulation of plasma lamellar calcium influx controls the senescence-associated secretory phenotype

Genes acting in longevity‐related pathways in the endoparasitoid, Pteromalus puparum

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