Senescent cells: an emerging target for diseases of ageing.
Bennett G. Childs,Martina Gluscevic,Darren J. Baker,Remi-Martin Laberge,Dan Marquess,Jamie Dananberg,Jan M. van Deursen +6 more
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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.read more
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FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence
Joana Catarina Macedo,Joana Catarina Macedo,Sara Vaz,Sara Vaz,Bjorn Bakker,Rui S. Ribeiro,Rui S. Ribeiro,Petra L. Bakker,José M. Escandell,Miguel Godinho Ferreira,René H. Medema,Floris Foijer,Elsa Logarinho,Elsa Logarinho +13 more
TL;DR: In aged cells, mitotic gene repression leads to increased chromosome mis-segregation and aneuploidy that triggers permanent cell cycle arrest and full senescence, and modulation of mitotic efficiency through FoxM1 is proposed as a potential strategy against aging and progeria syndromes.
Journal ArticleDOI
The curcumin analog EF24 is a novel senolytic agent.
TL;DR: EF24 selectively kills SCs by inducing SC apoptosis in a reactive oxygen species (ROS) production independent manner but associated with an increase in the proteasome degradation of the Bcl-2 anti-apoptotic protein family proteins known to play an important role in protecting SCs from apoptosis.
Journal ArticleDOI
Targetable mechanisms driving immunoevasion of persistent senescent cells link chemotherapy-resistant cancer to aging
Denise P. Muñoz,Steven M. Yannone,Anneleen Daemen,Yu Sun,Funda Vakar-Lopez,Misako Kawahara,Misako Kawahara,Adam Freund,Adam Freund,Francis Rodier,Jennifer D. Wu,Pierre Yves Desprez,Pierre Yves Desprez,David H. Raulet,Peter S. Nelson,Laura J. van't Veer,Judith Campisi,Judith Campisi,Jean-Philippe Coppe,Jean-Philippe Coppe +19 more
TL;DR: Cooperative mechanisms that orchestrate the immunoevasion and persistence of normal and cancer human SnCs through extracellular targeting of natural killer receptor signaling are identified and secretome-targeted therapeutic strategies to selectively eliminate and restore the clearance of the detrimental SnCs that actively persist after chemotherapy and accumulate at sites of aging pathologies are revealed.
Journal ArticleDOI
p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle.
Hui Che,Hui Che,Jie Li,You Li,Cheng Ma,Huan Liu,Jingyi Qin,Jianghui Dong,Jianghui Dong,Zhen Zhang,Cory J. Xian,Dengshun Miao,Liping Wang,Liping Wang,Yongxin Ren +14 more
TL;DR: It is demonstrated that p16 plays an important role in IVDD pathogenesis and that its deletion attenuates IVDD by promoting cell cycle and inhibiting SASP, cell senescence, and oxidative stress.
Journal ArticleDOI
Novel treatment strategies for chronic kidney disease: insights from the animal kingdom
Peter Stenvinkel,Johanna Painer,Makoto Kuro-o,Miguel A. Lanaspa,Walter Arnold,Thomas Ruf,Paul G. Shiels,Richard J. Johnson +7 more
TL;DR: Improved understanding of the susceptibility and protective mechanisms of these animals and others could provide insights into novel strategies to prevent and treat several human diseases, such as CKD and ageing-associated complications.
References
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