Stressing the cell cycle in senescence and aging

Chandler, Hollie; Peters, Gordon

doi:10.1016/j.ceb.2013.07.005

Cited by 104 publications

(101 citation statements)

References 73 publications

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“…Notably, four of the shared pathways in senescent MEFs and rVSMCs, including ubiquitin-mediated proteolysis, the Wnt signaling pathway, cell cycle, and regulation of the actin cytoskeleton (Fig. 1F,G), are linked to cellular senescence (Amberg et al 2012;Chandler and Peters 2013;Deschenes-Simard et al 2014;Hofmann et al 2014). Further examination of the genes preferring distal pA sites in mouse and rat revealed that these two species also possessed common genes undergoing APA regulation ( Fig.…”

Section: Global Lengthening Of 3 ′ Utrs Couples With Decreased Gene Ementioning

confidence: 99%

3′ UTR lengthening as a novel mechanism in regulating cellular senescence

Chen¹,

Lyu

Han³

et al. 2018

Genome Res.

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Cellular senescence has been viewed as a tumor suppression mechanism and also as a contributor to individual aging. Widespread shortening of 3 ′ untranslated regions (3 ′ UTRs) in messenger RNAs (mRNAs) by alternative polyadenylation (APA) has recently been discovered in cancer cells. However, the role of APA in the process of cellular senescence remains elusive. Here, we found that hundreds of genes in senescent cells tended to use distal poly(A) (pA) sites, leading to a global lengthening of 3 ′ UTRs and reduced gene expression. Genes that harbor longer 3 ′ UTRs in senescent cells were enriched in senescence-related pathways. Rras2, a member of the Ras superfamily that participates in multiple signal transduction pathways, preferred longer 3 ′ UTR usage and exhibited decreased expression in senescent cells. Depletion of Rras2 promoted senescence, while rescue of Rras2 reversed senescence-associated phenotypes. Mechanistically, splicing factor TRA2B bound to a core "AGAA" motif located in the alternative 3 ′ UTR of Rras2, thereby reducing the RRAS2 protein level and causing senescence. Both proximal and distal poly(A) signals showed strong sequence conservation, highlighting the vital role of APA regulation during evolution. Our results revealed APA as a novel mechanism in regulating cellular senescence.

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Section: Global Lengthening Of 3 ′ Utrs Couples With Decreased Gene Ementioning

confidence: 99%

3′ UTR lengthening as a novel mechanism in regulating cellular senescence

Chen¹,

Lyu

Han³

et al. 2018

Genome Res.

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show abstract

“…Various signaling pathways trigger senescence in response to oxidative stress, telomere erosion, replicative stress or genotoxic stress [11,12]. The molecular mechanisms underlying the heterogeneous triggers and phenotypes of senescence are complex and the recent identification of senescence associated microRNAs (miRNAs) has added another facet to the control of senescence.…”

Section: Introductionmentioning

confidence: 99%

“…Cellular aging or senescence is characterized by cell cycle arrest and an accumulation of CDK inhibitors such as p 16INK4a [11]. Various signaling pathways trigger senescence in response to oxidative stress, telomere erosion, replicative stress or genotoxic stress [11,12].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-22 Induces Endothelial Progenitor Cell Senescence by Targeting AKT3

Zheng

2014

Cell Physiol Biochem

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Objectives: Endothelial progenitor cells (EPCs) play an important role in postnatal neovascularization. The number and function of EPCs declines as part of aging-associated senescence, thereby potentially contributing to vascular pathologies. Here, we investigated the significance and molecular mechanisms of microRNA-22 (miR-22) governing EPC senescence. Methods: EPCs were isolated from human circulating mononuclear cells from healthy young and aged volunteers. Cell senescence, proliferation, migration and tube formation ability were detected by SA-β-gal staining assay, MTT assay, transwell assay and Matrigel-based angiogenesis assay. Gene and protein expression were analyzed by qRT-PCR and Western blot respectively. Results: We found that miR-22 was upregulated in aged EPCs. Overexpression of miR-22 in young EPCs induced cell senescence, decreased proliferation and migration, and impaired angiogenesis in vitro. Conversely, silencing of endogenous miR-22 led to decreased cell senescence, increased proliferation and migration, and improved angiogenesis. AKT3 was identified as a direct target of miR-22, and restoration of AKT3 expression attenuated the effects of miR-22 in young EPCs. Conclusion: Our results indicate that miR-22 induces EPC senescence by downregulating AKT3 expression, providing a potential novel target for the reversal of EPC dysfunction in angiogenesis.

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“…This is due in part to a progressive telomere shortening [ 9 ] and in part to development of genomic alterations that trigger the activity of antiproliferative genes. Among these, the gatekeeper P16INK4a has been studied in several experimental aging models as well as in clinical situations [ 13 ].…”

Section: Definition and Assessment Of Physiologic Agementioning

confidence: 99%

Systemic Treatment of Cancer in the Older-Aged Person

Balducci

2016

Ovarian Cancer in Elderly Patients

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Stressing the cell cycle in senescence and aging

Cited by 104 publications

References 73 publications

3′ UTR lengthening as a novel mechanism in regulating cellular senescence

3′ UTR lengthening as a novel mechanism in regulating cellular senescence

MicroRNA-22 Induces Endothelial Progenitor Cell Senescence by Targeting AKT3

Systemic Treatment of Cancer in the Older-Aged Person

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