Cellular Senescence: Defining a Path Forward

Cell, Год журнала: 2019, Номер 179(4), С. 813 - 827

Опубликована: Окт. 1, 2019

Язык: Английский

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Facing up to the global challenges of ageing

Nature, Год журнала: 2018, Номер 561(7721), С. 45 - 56

Опубликована: Авг. 30, 2018

Язык: Английский

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

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Март 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.

Язык: Английский

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Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines

Frontiers in Immunology, Год журнала: 2018, Номер 9

Опубликована: Апрель 9, 2018

Cytokine dysregulation is believed to play a key role in the remodeling of immune system at older age, with evidence pointing an inability fine-control systemic inflammation, which seems be marker unsuccessful aging. This reshaping cytokine expression pattern, progressive tendency toward pro-inflammatory phenotype has been called 'inflamm-aging'. Despite research there no clear understanding about causes 'inflamm-aging' that underpin most major age-related diseases including atherosclerosis, diabetes, Alzheimer's disease, rheumatoid arthritis, cancer and aging itself. While inflammation part normal repair response for healing, essential keeping us safe from bacterial viral infections noxious environmental agents, not all good. When becomes prolonged persists, it can become damaging destructive. Several common molecular pathways have identified are associated both low-grade inflammation. The change redox balance, increase senescent cells SASP decline effective autophagy trigger inflammasome, suggest may possible delay itself by suppressing mechanisms or improving timely resolution Conversely learning genetic long-lived cohorts who exemplify good quality Here we will discuss some current ideas highlight appear contribute imbalance dysregulation, 'inflammageing' parainflammation. Evidence these findings drawn cardiovascular disease two

Язык: Английский

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Senescence and the SASP: many therapeutic avenues

Genes & Development, Год журнала: 2020, Номер 34(23-24), С. 1565 - 1576

Опубликована: Дек. 1, 2020

Cellular senescence is a stress response that elicits permanent cell cycle arrest and triggers profound phenotypic changes such as the production of bioactive secretome, referred to senescence-associated secretory phenotype (SASP). Acute induction protects against cancer limits fibrosis, but lingering senescent cells drive age-related disorders. Thus, targeting delay aging limit dysfunction, known “senotherapy,” gaining momentum. While drugs selectively kill cells, termed “senolytics” are major focus, SASP-centered approaches emerging alternatives target diseases. Here, we summarize regulation functions SASP highlight therapeutic potential modulation complimentary or an alternative current senolytic approaches.

Язык: Английский

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Mechanisms and functions of cellular senescence

Journal of Clinical Investigation, Год журнала: 2018, Номер 128(4), С. 1238 - 1246

Опубликована: Апрель 1, 2018

Cellular senescence is a highly stable cell cycle arrest that elicited in response to different stresses. By imposing growth arrest, limits the replication of old or damaged cells. Besides exiting cycle, senescent cells undergo many other phenotypic alterations such as metabolic reprogramming, chromatin rearrangement, autophagy modulation. In addition, produce and secrete complex combination factors, collectively referred senescence-associated secretory phenotype, mediate most their non–cell-autonomous effects. Because influence outcome variety physiological pathological processes, including cancer age-related diseases, pro-senescent anti-senescent therapies are actively being explored. this Review, we discuss mechanisms regulating aspects phenotype functional implications. This knowledge essential improve identification characterization vivo will help develop rational strategies modulate program for therapeutic benefit.

Язык: Английский

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<p>Reactive Oxygen Species: Drivers of Physiological and Pathological Processes</p>

Journal of Inflammation Research, Год журнала: 2020, Номер Volume 13, С. 1057 - 1073

Опубликована: Дек. 1, 2020

Abstract: Since the Great Oxidation Event, about 2.4 billion years ago, Earth is immersed in an oxidizing atmosphere. Thus, it has been proposed that excess oxygen, originally a waste product of photosynthetic cyanobacteria, induced oxidative stress and production reactive oxygen species (ROS), which have since acted as fundamental drivers biologic evolution eukaryogenesis. Indeed, throughout organism's lifespan, ROS affect directly (as mutagens) or indirectly messengers regulators) all structural functional components cells, many aspects cell biology. Whether left unchecked by protective antioxidant systems, not only cause genomic mutations but also induce irreversible modification proteins (protein oxidation peroxidation), lipids glycans (advanced lipoxidation glycation end products), impairing their function promoting disease death. Conversely, low-level local play important role both redox-signaling molecules wide spectrum pathways involved maintenance cellular homeostasis (MAPK/ERK, PTK/PTP, PI3K-AKT-mTOR), regulating key transcription factors (NFκB/IκB, Nrf2/KEAP1, AP-1, p53, HIF-1). Consequently, can shape variety functions, including proliferation, differentiation, migration apoptosis. In this review, we will give brief overview relevance physiological pathological processes, particularly inflammation aging. In-depth knowledge molecular mechanisms actuation influence under steady-state stressful conditions pave way for development novel therapeutic interventions. This mitigate harmful outcomes onset progression chronic inflammatory age-related diseases. Keywords: species, stress,

Язык: Английский

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How the ageing microenvironment influences tumour progression

Nature reviews. Cancer, Год журнала: 2019, Номер 20(2), С. 89 - 106

Опубликована: Дек. 13, 2019

Язык: Английский

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Linking cellular stress responses to systemic homeostasis

Nature Reviews Molecular Cell Biology, Год журнала: 2018, Номер 19(11), С. 731 - 745

Опубликована: Окт. 10, 2018

Язык: Английский

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Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition

Nature Communications, Год журнала: 2019, Номер 10(1)

Опубликована: Июнь 3, 2019

Senescent cells accumulate in human tissues during ageing and contribute to age-related pathologies. The mechanisms responsible for their accumulation are unclear. Here we show that senescent dermal fibroblasts express the non-classical MHC molecule HLA-E, which interacts with inhibitory receptor NKG2A expressed by NK highly differentiated CD8

Язык: Английский

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