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Senescent cells: an emerging target for diseases of ageing.

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TLDR
Therapeutic strategies that safely interfere with the detrimental effects of cellular senescence, such as the selective elimination of senescent cells (SNCs) or the disruption of the SNC secretome, are gaining significant attention, with several programmes now nearing human clinical studies.
Abstract
Chronological age represents the single greatest risk factor for human disease. One plausible explanation for this correlation is that mechanisms that drive ageing might also promote age-related diseases. Cellular senescence, which is a permanent state of cell cycle arrest induced by cellular stress, has recently emerged as a fundamental ageing mechanism that also contributes to diseases of late life, including cancer, atherosclerosis and osteoarthritis. Therapeutic strategies that safely interfere with the detrimental effects of cellular senescence, such as the selective elimination of senescent cells (SNCs) or the disruption of the SNC secretome, are gaining significant attention, with several programmes now nearing human clinical studies.

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Journal ArticleDOI

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Lorenzo Galluzzi, +186 more
TL;DR: The Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives.
Journal Article

Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor

TL;DR: Coppe et al. as mentioned in this paper showed that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy, including interleukin (IL)-6 and IL-8.
Journal ArticleDOI

Reactive astrocyte nomenclature, definitions, and future directions

Carole Escartin, +88 more
- 15 Feb 2021 - 
TL;DR: In this article, the authors point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic vs-neuroprotective or A1-vs.A2.
Journal ArticleDOI

Mitochondrial metabolism and cancer.

TL;DR: The cancer cell-intrinsic and cell-extrinsics mechanisms through which mitochondria influence all steps of oncogenesis are reviewed, with a focus on the therapeutic potential of targeting mitochondrial metabolism for cancer therapy.
Journal ArticleDOI

Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline

TL;DR: In a mouse model of tau-dependent neurodegenerative disease, the clearance of senescent glial cells prevents the degeneration of cortical and hippocampal neurons and preserves cognitive function, suggesting that targeting senescent cells may provide a therapeutic avenue for the treatment of these pathologies.
References
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Journal ArticleDOI

DNMT3a plays a role in switches between doxorubicin-induced senescence and apoptosis of colorectal cancer cells.

TL;DR: It is demonstrated that DNMT3a impacts the expression of p21 and plays a role in determining the Dox‐induced senescence and apoptosis in HCT116 cells.
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Senescence-enhanced oxidative stress is associated with deficiency of mitochondrial cytochrome c oxidase in vascular endothelial cells.

TL;DR: Data demonstrate that deficiency of complex IV in senescent cells enhances oxidative and nitrosative stress, which may be responsible for senescence-induced endothelial cell loss and dysfunction.
Journal ArticleDOI

Absence of p53-dependent apoptosis leads to UV radiation hypersensitivity, enhanced immunosuppression and cellular senescence

TL;DR: It is found that mice harboring a hypomorphic mutant p53, R172P, a mutation that abrogates p53-mediated apoptosis while keeping cell cycle control mostly intact, are more susceptible to ultraviolet-B (UVB)-induced skin damage, inflammation, and immunosuppression than wild-type mice.
Journal ArticleDOI

HMGA2 expression in white adipose tissue linking cellular senescence with diabetes

TL;DR: Investigating the gene expression of HMGA2, p14Arf, CDKN1A, and BAX in human abdominal subcutaneous white adipose tissue from 157 patients found a significant higherHMGA2 expression in obese individuals than in non-obese patients, and the HMGA1 expression in white adiposity in patient with type 2 diabetes was significantly higher than in nondiabetic patients.
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