Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis DOI Open Access
Mandy O. J. Grootaert, Manon Moulis, Lynn Roth

et al.

Cardiovascular Research, Journal Year: 2018, Volume and Issue: 114(4), P. 622 - 634

Published: Jan. 17, 2018

In the present review, we describe causes and consequences of loss vascular smooth muscle cells (VSMCs) or their function in advanced atherosclerotic plaques discuss possible mechanisms such as cell death senescence, induction autophagy to promote survival. We also highlight potential use pharmacological modulators these processes limit plaque progression and/or improve stability. VSMCs play a pivotal role atherogenesis. Loss via initiation leads fibrous cap thinning promotes necrotic core formation calcification. VSMC apoptosis is induced by pro-inflammatory cytokines, oxidized low density lipoprotein, high levels nitric oxide mechanical injury. Apoptotic are characterized thickened basal lamina surrounding cytoplasmic remnants VSMC. Inefficient clearance apoptotic results secondary necrosis subsequent inflammation. A critical determinant stress response phenotypic switching autophagy, which activated various stimuli, including reactive oxygen lipid species, growth factors metabolic stress. Successful stimulates survival, whereas reduced age-related changes vasculature. Recently, an interesting link between senescence has been uncovered. Defective accelerates not only development stress-induced premature but atherogenesis, albeit without worsening atherosclerosis likely result replicative DNA damaging oxidative stress-inducing stimuli. The finding that can further illustrates normal, adequate crucial protecting vessel wall against atherosclerosis.

Language: Английский

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018 DOI Creative Commons
Lorenzo Galluzzi, Ilio Vitale, Stuart A. Aaronson

et al.

Cell Death and Differentiation, Journal Year: 2018, Volume and Issue: 25(3), P. 486 - 541

Published: Jan. 23, 2018

Over the past decade, Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for definition and interpretation of cell death from morphological, biochemical, functional perspectives. Since field continues to expand novel mechanisms that orchestrate multiple pathways are unveiled, we propose an updated classification subroutines focusing mechanistic essential (as opposed correlative dispensable) aspects process. As provide molecularly oriented definitions terms including intrinsic apoptosis, extrinsic mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic death, NETotic lysosome-dependent autophagy-dependent immunogenic cellular senescence, mitotic catastrophe, discuss utility neologisms refer highly specialized instances these processes. The mission NCCD is a widely accepted nomenclature in support continued development field.

Language: Английский

Citations

5365
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan DOI
Darren J. Baker, Bennett G. Childs, Matej Durik

et al.

Nature, Journal Year: 2016, Volume and Issue: 530(7589), P. 184 - 189

Published: Feb. 1, 2016

Language: Английский

Citations

2420
Cellular Senescence: Defining a Path Forward DOI Creative Commons
Vassilis G. Gorgoulis, Peter D. Adams, Andrea Alimonti

et al.

Cell, Journal Year: 2019, Volume and Issue: 179(4), P. 813 - 827

Published: Oct. 1, 2019

Language: Английский

Citations

2272
Senescence in Health and Disease DOI Creative Commons
Shenghui He, Norman E. Sharpless

Cell, Journal Year: 2017, Volume and Issue: 169(6), P. 1000 - 1011

Published: June 1, 2017

Language: Английский

Citations

1444
Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse DOI Open Access
Marco Demaria,

Monique N. O’Leary,

Jianhui Chang

et al.

Cancer Discovery, Journal Year: 2016, Volume and Issue: 7(2), P. 165 - 176

Published: Dec. 16, 2016

Cellular senescence suppresses cancer by irreversibly arresting cell proliferation. Senescent cells acquire a proinflammatory senescence-associated secretory phenotype. Many genotoxic chemotherapies target proliferating nonspecifically, often with adverse reactions. In accord prior work, we show that several chemotherapeutic drugs induce of primary murine and human cells. Using transgenic mouse permits tracking eliminating senescent cells, therapy-induced (TIS) persist contribute to local systemic inflammation. Eliminating TIS reduced short- long-term effects the drugs, including bone marrow suppression, cardiac dysfunction, recurrence, physical activity strength. Consistent our findings in mice, risk chemotherapy-induced fatigue was significantly greater humans increased expression marker T chemotherapy. These suggest can cause certain chemotherapy side effects, providing new reduce toxicity anticancer treatments.Many have debilitating also cellular normal tissues. The remain chronically present where they promote inflammation causes or exacerbates many Cancer Discov; 7(2); 165-76. ©2016 AACR.This article is highlighted This Issue feature, p. 115.

Language: Английский

Citations

1131
Wound healing: cellular mechanisms and pathological outcomes DOI Creative Commons
Holly N. Wilkinson, Matthew J. Hardman

Open Biology, Journal Year: 2020, Volume and Issue: 10(9)

Published: Sept. 1, 2020

Wound healing is a complex, dynamic process supported by myriad of cellular events that must be tightly coordinated to efficiently repair damaged tissue. Derangement in wound-linked behaviours, as occurs with diabetes and ageing, can lead impairment the formation chronic, non-healing wounds. These wounds are significant socioeconomic burden due their high prevalence recurrence. Thus, there an urgent requirement for improved biological clinical understanding mechanisms underpin wound repair. Here, we review basis tissue discuss how current emerging pathology could inform future development efficacious therapies.

Language: Английский

Citations

1123
Facing up to the global challenges of ageing DOI
Linda Partridge, Joris Deelen, P. Eline Slagboom

et al.

Nature, Journal Year: 2018, Volume and Issue: 561(7721), P. 45 - 56

Published: Aug. 30, 2018

Language: Английский

Citations

1098
The Sleep-Immune Crosstalk in Health and Disease DOI Creative Commons
Luciana Besedovsky, Tanja Lange, Monika Haack

et al.

Physiological Reviews, Journal Year: 2019, Volume and Issue: 99(3), P. 1325 - 1380

Published: March 28, 2019

Sleep and immunity are bidirectionally linked. Immune system activation alters sleep, sleep in turn affects the innate adaptive arm of our body’s defense system. Stimulation immune by microbial challenges triggers an inflammatory response, which, depending on its magnitude time course, can induce increase duration intensity, but also a disruption sleep. Enhancement during infection is assumed to feedback promote host defense. Indeed, various parameters, associated with reduced risk, improve outcome vaccination responses. The induction hormonal constellation that supports functions one likely mechanism underlying immune-supporting effects In absence infectious challenge, appears homeostasis through several mediators, such as cytokines. This notion supported findings prolonged deficiency (e.g., short duration, disturbance) lead chronic, systemic low-grade inflammation diseases have component, like diabetes, atherosclerosis, neurodegeneration. Here, we review available data this regulatory sleep-immune crosstalk, point out methodological challenges, suggest questions open for future research.

Language: Английский

Citations

1076
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype DOI Creative Commons

Ruchi Kumari,

Parmjit Jat

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

Citations

1052
Senescent cells: an emerging target for diseases of ageing DOI
Bennett G. Childs,

Martina Gluscevic,

Darren J. Baker

et al.

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

Published: July 21, 2017

Language: Английский

Citations

1022