Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment

Nature Medicine, Journal Year: 2017, Volume and Issue: 23(6), P. 775 - 781

Published: April 24, 2017

Language: Английский

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Cellular senescence mediates fibrotic pulmonary disease

Nature Communications, Journal Year: 2017, Volume and Issue: 8(1)

Published: Feb. 23, 2017

Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by interstitial remodelling, leading to compromised lung function. Cellular senescence markers are detectable within IPF tissue and senescent cell deletion rejuvenates health in aged mice. Whether how cells regulate or if their removal may be an efficacious intervention strategy unknown. Here we demonstrate elevated abundance of biomarkers lung, with p16 expression increasing severity. We show that the secretome fibroblasts, which selectively killed senolytic cocktail, dasatinib plus quercetin (DQ), fibrogenic. Leveraging bleomycin-injury model, early-intervention suicide-gene-mediated ablation improves function physical health, although visibly unaltered. DQ treatment replicates benefits transgenic clearance. Thus, our findings establish fibrotic mediated, part, cells, can targeted improve

Language: Английский

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Autophagy maintains stemness by preventing senescence

Nature, Journal Year: 2016, Volume and Issue: 529(7584), P. 37 - 42

Published: Jan. 1, 2016

Language: Английский

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Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: March 29, 2021

Cellular senescence is a stable cell cycle arrest that can be triggered in normal cells response to various intrinsic and extrinsic stimuli, as well developmental signals. Senescence considered highly dynamic, multi-step process, during which the properties of senescent continuously evolve diversify context dependent manner. It associated with multiple cellular molecular changes distinct phenotypic alterations, including proliferation unresponsive mitogenic stimuli. Senescent remain viable, have alterations metabolic activity undergo dramatic gene expression develop complex senescence-associated secretory phenotype. compromise tissue repair regeneration, thereby contributing toward aging. Removal attenuate age-related dysfunction extend health span. also act potent anti-tumor mechanism, by preventing potentially cancerous cells. program acts double-edged sword, both beneficial detrimental effects on organism, an example evolutionary antagonistic pleiotropy. Activation p53/p21 WAF1/CIP1 p16 INK4A /pRB tumor suppressor pathways play central role regulating senescence. Several other recently been implicated mediating Herein we review mechanisms underlie growth particular focus why stop dividing, stability arrest, hypersecretory phenotype how different are all integrated.

Language: Английский

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Senescent cells: an emerging target for diseases of ageing

Nature Reviews Drug Discovery, Journal Year: 2017, Volume and Issue: 16(10), P. 718 - 735

Published: July 21, 2017

Language: Английский

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Forging a signature of in vivo senescence

Nature reviews. Cancer, Journal Year: 2015, Volume and Issue: 15(7), P. 397 - 408

Published: June 24, 2015

Language: Английский

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Mechanisms of Renal Fibrosis

Annual Review of Physiology, Journal Year: 2017, Volume and Issue: 80(1), P. 309 - 326

Published: Oct. 25, 2017

Tubulointerstitial fibrosis is a chronic and progressive process affecting kidneys during aging in kidney disease (CKD), regardless of cause. CKD renal affect half adults above age 70 10% the world's population. Although no targeted therapy yet exists to slow fibrosis, number important recent advances have clarified cellular molecular mechanisms underlying disease. In this review, I highlight these with focus on cells pathways that may be amenable therapeutic targeting. discuss pathologic changes regulating interstitial myofibroblast activation, including profibrotic proinflammatory paracrine signals secreted by epithelial after either acute or injury. conclude highlighting novel targets approaches particular promise for development new treatments patients fibrotic

Language: Английский

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Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence

Nature Cell Biology, Journal Year: 2017, Volume and Issue: 19(9), P. 1061 - 1070

Published: July 31, 2017

Language: Английский

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Cyclic Decidualization of the Human Endometrium in Reproductive Health and Failure

Endocrine Reviews, Journal Year: 2014, Volume and Issue: 35(6), P. 851 - 905

Published: Aug. 20, 2014

Decidualization denotes the transformation of endometrial stromal fibroblasts into specialized secretory decidual cells that provide a nutritive and immunoprivileged matrix essential for embryo implantation placental development. In contrast to most mammals, decidualization human endometrium does not require implantation. Instead, this process is driven by postovulatory rise in progesterone levels increasing local cAMP production. response falling levels, spontaneous causes menstrual shedding cyclic regeneration endometrium. A growing body evidence indicates shift from embryonic maternal control represents pivotal evolutionary adaptation challenge posed invasive chromosomally diverse embryos. This concept predicated on ability decidualizing respond individual embryos manner either promotes further development or facilitates early rejection. Furthermore, menstruation involves stem cell recruitment renders intrinsically capable adapting its maximize reproductive success. Here we review endocrine, paracrine, autocrine cues tightly govern differentiation process. activation various signaling pathways genome-wide chromatin remodeling, evolutionarily conserved transcriptional factors gain access decidua-specific regulatory circuitry. Once initiated, poised transit through distinct phenotypic phases underpin receptivity, selection, and, ultimately, resolution pregnancy. We discuss how disorders subvert programming, initiation, progression compromise health predispose pregnancy failure.

Language: Английский

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ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age‐Related Diseases

Oxidative Medicine and Cellular Longevity, Journal Year: 2016, Volume and Issue: 2016(1)

Published: Jan. 1, 2016

The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression metabolic control, rate has been associated with production of high levels Reactive Oxygen Species (ROS) and/or Nitrosative (RNS). Specific increases ROS level have demonstrated as potentially critical for induction maintenance cell senescence process. Causal connection between ROS, aging, age‐related pathologies, is studied intensely. Senescent cells proposed a target interventions delay related diseases or improve treatment. Therapeutic towards senescent might allow restoring health curing that share basal processes, rather than each disease separate symptomatic way. Here, we review observations on ability inducing through novel mechanisms underpin processes. Particular emphasis addressed involvement epigenetic regulation aim individuate specific pathways, which promote healthy lifespan aging.

Language: Английский

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