Senescent cells harbour features of the cancer epigenome
Hazel A Cruickshanks,Hazel A Cruickshanks,Tony McBryan,David M. Nelson,Nathan D. VanderKraats,Parisha P. Shah,John van Tuyn,Taranjit Singh Rai,Taranjit Singh Rai,Claire Brock,Greg Donahue,Donncha S. Dunican,Mark E. Drotar,Richard R. Meehan,John R. Edwards,Shelley L. Berger,Peter D. Adams +16 more
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TLDR
It is shown by whole-genome single-nucleotide bisulfite sequencing that replicative senescent human cells exhibit widespread DNA hypomethylation and focal hypermethylation, and this ‘reprogrammed’ methylation landscape is largely retained when cells bypass senescence.Abstract:
Altered DNA methylation and associated destabilization of genome integrity and function is a hallmark of cancer. Replicative senescence is a tumour suppressor process that imposes a limit on the proliferative potential of normal cells that all cancer cells must bypass. Here we show by whole-genome single-nucleotide bisulfite sequencing that replicative senescent human cells exhibit widespread DNA hypomethylation and focal hypermethylation. Hypomethylation occurs preferentially at gene-poor, late-replicating, lamin-associated domains and is linked to mislocalization of the maintenance DNA methyltransferase (DNMT1) in cells approaching senescence. Low-level gains of methylation are enriched in CpG islands, including at genes whose methylation and silencing is thought to promote cancer. Gains and losses of methylation in replicative senescence are thus qualitatively similar to those in cancer, and this ‘reprogrammed’ methylation landscape is largely retained when cells bypass senescence. Consequently, the DNA methylome of senescent cells might promote malignancy, if these cells escape the proliferative barrier. Cancer is associated with altered DNA methylation. Using whole-genome single-nucleotide sequencing, Adams and colleagues reveal that senescent cells, as well as cells that have bypassed senescence through p53 and pRB inactivation, exhibit methylation changes similar to those seen in cancer.read more
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Cellular Senescence: Defining a Path Forward
Vassilis G. Gorgoulis,Peter D. Adams,Andrea Alimonti,Dorothy C. Bennett,Oliver Bischof,Cleo L. Bishop,Judith Campisi,Manuel Collado,Konstantinos Evangelou,Gerardo Ferbeyre,Jesús Gil,Eiji Hara,Valery Krizhanovsky,Diana Jurk,Andrea B. Maier,Masashi Narita,Laura J. Niedernhofer,João F. Passos,Paul D. Robbins,Clemens A. Schmitt,John M. Sedivy,Konstantinos Vougas,Thomas von Zglinicki,Daohong Zhou,Manuel Serrano,Marco Demaria +25 more
TL;DR: A consensus from the International Cell Senescence Association (ICSA) is presented, defining and discussing key cellular and molecular features of senescence and offering recommendations on how to use them as biomarkers.
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ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases.
TL;DR: Observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes are reviewed, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging.
Journal ArticleDOI
Cellular senescence in ageing: from mechanisms to therapeutic opportunities
TL;DR: The mechanisms and modulators of cellularsenescence establishment and induction of a senescence-associated secretory phenotype are discussed, and the potential of senolytic and senomorphic therapies in ageing and associated diseases is provided.
Journal ArticleDOI
Epigenetic Mechanisms of Longevity and Aging.
TL;DR: This review provides a comprehensive overview of epigenetic studies from invertebrate organisms, vertebrate models, tissues, and in vitro systems and establishes links between common operative aging pathways and hallmark chromatin signatures that can be used to identify "druggable" targets to counter human aging and age-related disease.
Journal ArticleDOI
Pioneer transcription factors in cell reprogramming
TL;DR: Understanding the means by which pioneer factors can engage closed chromatin and how heterochromatin can prevent such binding promises to advance the ability to reprogram cell fates at will is the topic of this review.
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