Reorganization of chromosome architecture in replicative cellular senescence

Criscione, Steven W.; Cecco, Marco De; Siranosian, Benjamin A.; Zhang, Yue; Kreiling, Jill A.; Sedivy, John M.; Neretti, Nicola

doi:10.1126/sciadv.1500882

Cited by 125 publications

(133 citation statements)

References 67 publications

(123 reference statements)

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“…Recently, analysis of 3D chromosomal architecture using combined biochemical, cytological, and computational techniques has revealed significant decreases in volume, and increases in chromosome compaction during cellular senescence [227]. This unique senescent chromosomal signature is attributed to an increase in short-range chromatin contacts and genome-wide contraction of chromosome arms.…”

Section: Redox Control Of Sasp and Age-related Pathologiesmentioning

confidence: 99%

Redox control of senescence and age-related disease

2017

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The signaling networks that drive the aging process, associated functional deterioration, and pathologies has captured the scientific community's attention for decades. While many theories exist to explain the aging process, the production of reactive oxygen species (ROS) provides a signaling link between engagement of cellular senescence and several age-associated pathologies. Cellular senescence has evolved to restrict tumor progression but the accompanying senescence-associated secretory phenotype (SASP) promotes pathogenic pathways. Here, we review known biological theories of aging and how ROS mechanistically control senescence and the aging process. We also describe the redox-regulated signaling networks controlling the SASP and its important role in driving age-related diseases. Finally, we discuss progress in designing therapeutic strategies that manipulate the cellular redox environment to restrict age-associated pathology.

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Section: Redox Control Of Sasp and Age-related Pathologiesmentioning

confidence: 99%

Redox control of senescence and age-related disease

2017

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“…Changes in chromosome organization identified in RS cells by Hi-C were intermediate between the OIS and HGPS cells [63]. Genome-wide, RS cells displayed a global increase in short-range contacts.…”

Section: Senescent Cells Display Extensive Changes In Chromatin Strucmentioning

confidence: 99%

“…In contrast to HGPS, which showed a dramatic loss of compartmentalization, the overall 3D organization of chromosomes was maintained in RS cells. By conducting a variety of complementary experiments including chromosome painting and 3D DNA FISH, it was concluded that the increased short-range contacts could be attributed to a decrease in the volume occupied by chromosome arms (Figure 1) [63]. This was in stark contrast to the behavior of centromeres, which showed significant decondensation as described below.…”

Section: Senescent Cells Display Extensive Changes In Chromatin Strucmentioning

confidence: 99%

The Chromatin Landscape of Cellular Senescence

2016

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Cellular senescence, an irreversible growth arrest triggered by a variety of stressors, plays important roles in normal physiology and tumor suppression, but accumulation of senescent cells with age contributes to the functional decline of tissues. Senescent cells undergo dramatic alterations to their chromatin landscape that affect genome accessibility and their transcriptional program. These include the loss of DNA-nuclear lamina interactions, the distension of centromeres, and changes in chromatin composition that can lead to the activation of retrotransposons. Here we discuss these findings, as well as recent advances in microscopy and genomics that have revealed the importance of the higher-order spatial organization of the genome in defining and maintaining the senescent state.

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“…Repositioning of the heterochromatin regions from the periphery to the nuclear center generates novel genetic interaction domains, largely known as senescence-associated heterochromatic foci (SAHF), which are usually associated with repressive histone marks, such as histone 3 lysine 9 trimethylation (H3K9me3) [10]. A whole-genome chromosome conformation capture (Hi-C) analysis in human senescent fibroblasts has unraveled that certain topologically associated domains (TAD) are relocated acquiring novel short-range interactions while losing long-range interactions within chromosomes [15]. Another Hi-C study of senescent fibroblasts has shown that the local genetic interactions within SAHF domains are weakened [14].…”

Section: Nuclear Reorganization: Chromatin Remodeling and The Nuclearmentioning

confidence: 99%

Epigenetic Modifications upon Senescence of Mesenchymal Stem Cells

2016

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Cellular senescence is a continuous and highly organized process that alters the intricate genomic network in order to maintain cellular homeostasis. It occurs in all primary cell cultures-including mesenchymal stem cells (MSCs), which are concurrently tested for a wide variety of clinical applications. Differentiation potential as well as paracrine secretion of MSCs is severely affected by cellular senescence. There is a growing perception that nuclear reorganization and epigenetic modifications contribute to trigger and maintain functional differences in long-term culture. In this review, we discuss molecular and epigenetic aspects that evoke functional changes in cellular aging-indicating that the underlying process is not only an accumulation of cellular defects, but rather epigenetically orchestrated.

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Reorganization of chromosome architecture in replicative cellular senescence

Abstract: Senescent cells acquire a unique chromosome architecture characterized by a genome-wide shrinkage of chromosome arms.

Cited by 125 publications

References 67 publications

Redox control of senescence and age-related disease

Redox control of senescence and age-related disease

The Chromatin Landscape of Cellular Senescence

Epigenetic Modifications upon Senescence of Mesenchymal Stem Cells

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