Hallmarks of Cellular Senescence

Hernandez‐Segura, Alejandra; Nehme, Jamil; Demaria, Marco

doi:10.1016/j.tcb.2018.02.001

Cited by 1,530 publications

(1,330 citation statements)

References 161 publications

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“…Using DAVID, we found that the following terms were enriched across the 1,661 genes in the PPI Table 33). These results are all in line with previously described hallmarks of cellular senescence (Hernandez-Segura et al, 2018).…”

Section: The Protein-protein Interaction Network Associated With Cssupporting

confidence: 93%

A Multidimensional Systems Biology Analysis of Cellular Senescence in Ageing and Disease

Avelar

Ortega

Tăcutu

et al. 2019

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Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of ageing and has been linked to ageing-related diseases like cancer. Senescent cells have been shown to accumulate in tissues of aged organisms which in turn can lead to chronic inflammation. Many genes have been associated with cell senescence, yet a comprehensive understanding of cell senescence pathways is still lacking. To this end, we created CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes associated with cellular senescence, and performed various integrative and functional analyses. We observed that genes promoting cell senescence tend to be overexpressed with age in human tissues and are also significantly overrepresented in anti-longevity and tumour-suppressor gene databases.By contrast, genes inhibiting cell senescence overlapped with pro-longevity genes and oncogenes.Furthermore, an evolutionary analysis revealed a strong conservation of senescence-associated genes in mammals, but not in invertebrates. Using the CellAge genes as seed nodes, we also built protein-protein interaction and co-expression networks. Clusters in the networks were enriched for cell cycle and immunological processes. Network topological parameters also revealed novel potential senescence-associated regulators. We then used siRNAs and observed that of 26 candidates tested, 19 induced markers of senescence. Overall, our work provides a new resource for researchers to study cell senescence and our systems biology analyses provide new insights and novel genes regarding cell senescence.

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Section: The Protein-protein Interaction Network Associated With Cssupporting

confidence: 93%

A Multidimensional Systems Biology Analysis of Cellular Senescence in Ageing and Disease

Avelar

Ortega

Tăcutu

et al. 2019

Preprint

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“…Several recent studies have suggested that treatment with DEX in 2D cell culture resulted in increased cellular senescence, particularly with increased and sustained DEX doses . Senescent cells are growth‐arrested cells that exhibit reduced activity, induction of anti‐apoptotic genes and enhanced secretion of pro‐inflammatory factors through the senescence‐associated secretory phenotype . While the reduction in certain aspects of cell activity with DEX treatment in the present study does appear to agree with the onset of cellular quiescence, or perhaps senescence, this has not yet been confirmed in our culture system and will be a focus of future work.…”

Section: Discussioncontrasting

confidence: 55%

Lose‐Dose Administration of Dexamethasone Is Beneficial in Preventing Secondary Tendon Damage in a Stress‐Deprived Joint Injury Explant Model

Connizzo

Grodzinsky

2019

Journal Orthopaedic Research

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Secondary joint damage is the process by which a single injury can lead to detrimental changes in adjacent tissue structures, typically through the spread of inflammatory responses. We recently developed an in vitro model of secondary joint damage using a murine rotator cuff explant system, in which injuries to muscle and bone cause massive cell death in otherwise uninjured tendon. The purpose of the present study was to test the ability cytokine‐targeted and broad‐spectrum therapeutics to prevent cell death and tissue degeneration associated with secondary joint damage. We treated injured bone‐tendon‐muscle explants with either interleukin‐1 receptor antagonist, etanercept, or dexamethasone (DEX) for up to 7 days in culture. Only the low‐dose DEX treatment was able to prevent cell death and tissue degeneration. We then identified a critical window between 24 and 72 h following injury for maximal benefit of DEX treatment through timed administration experiments. Finally, we performed two tendon‐only explant studies to identify mechanistic effects on tendon health. Interestingly, DEX did not prevent cell death and degeneration in a model of cytokine‐induced damage, suggesting other targets of DEX activity. Future studies will aim to identify factors in joint inflammation that may be targeted by DEX treatment, as well as to investigate novel delivery strategies. Statement of clinical significance: Overall, this work demonstrates beneficial effects of DEX administration on preventing tenocyte death and extracellular matrix degeneration in an explant model of secondary joint damage, supporting the clinical use of low‐dose glucocorticoids for short‐term treatment of joint inflammation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:139–149, 2020

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“…Cellular senescence is a metabolically active state of cell cycle arrest Zhang, 2014, 2015;Dorr et al, 2013;Hernandez-Segura et al, 2018;Wiley and Campisi, 2016). Activation of oncogenes induces senescence to suppress transformation and tumorigenesis (termed oncogene-induced senescence, OIS) (Perez-Mancera et al,…”

Section: Introductionmentioning

confidence: 99%

Suppression of p16 induces mTORC1-mediated nucleotide metabolic reprogramming

Buj

Chen

Dahl

et al. 2018

Preprint

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2 SummaryReprogrammed metabolism and cell cycle dysregulation are two cancer hallmarks. p16 is a cell cycle inhibitor and tumor suppressor that is upregulated during oncogeneinduced senescence (OIS). Loss of p16 allows for uninhibited cell cycle progression, bypass of OIS, and tumorigenesis. Whether p16 loss affects pro-tumorigenic metabolism is unclear. We report that suppression of p16 plays a central role in

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Hallmarks of Cellular Senescence

Cited by 1,530 publications

References 161 publications

A Multidimensional Systems Biology Analysis of Cellular Senescence in Ageing and Disease

A Multidimensional Systems Biology Analysis of Cellular Senescence in Ageing and Disease

Lose‐Dose Administration of Dexamethasone Is Beneficial in Preventing Secondary Tendon Damage in a Stress‐Deprived Joint Injury Explant Model

Suppression of p16 induces mTORC1-mediated nucleotide metabolic reprogramming

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