Role of hypoxia in cellular senescence

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F23%3A50020515" target="_blank" >RIV/62690094:18470/23:50020515 - isvavai.cz</a>

Alternative codes found

RIV/62156489:43210/23:43923673 RIV/00179906:_____/23:10469223

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S1043661823001974?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S1043661823001974?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.phrs.2023.106841" target="_blank" >10.1016/j.phrs.2023.106841</a>

Result language

angličtina

Original language name

Role of hypoxia in cellular senescence

Original language description

Senescent cells persist and continuously secrete proinflammatory and tissue-remodeling molecules that poison surrounding cells, leading to various age-related diseases, including diabetes, atherosclerosis, and Alzheimer&apos;s disease. The underlying mechanism of cellular senescence has not yet been fully explored. Emerging evidence indicates that hypoxia is involved in the regulation of cellular senescence. Hypoxia-inducible factor (HIF)− 1α accumulates under hypoxic conditions and regulates cellular senescence by modulating the levels of the senescence markers p16, p53, lamin B1, and cyclin D1. Hypoxia is a critical condition for maintaining tumor immune evasion, which is promoted by driving the expression of genetic factors (such as p53 and CD47) while triggering immunosenescence. Under hypoxic conditions, autophagy is activated by targeting BCL-2/adenovirus E1B 19-kDa interacting protein 3, which subsequently induces p21WAF1/CIP1 as well as p16Ink4a and increases β-galactosidase (β-gal) activity, thereby inducing cellular senescence. Deletion of the p21 gene increases the activity of the hypoxia response regulator poly (ADP-ribose) polymerase-1 (PARP-1) and the level of nonhomologous end joining (NHEJ) proteins, repairs DNA double-strand breaks, and alleviates cellular senescence. Moreover, cellular senescence is associated with intestinal dysbiosis and an accumulation of D-galactose derived from the gut microbiota. Chronic hypoxia leads to a striking reduction in the amount of Lactobacillus and D-galactose-degrading enzymes in the gut, producing excess reactive oxygen species (ROS) and inducing senescence in bone marrow mesenchymal stem cells. Exosomal microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) play important roles in cellular senescence. miR-424–5p levels are decreased under hypoxia, whereas lncRNA-MALAT1 levels are increased, both of which induce cellular senescence. The present review focuses on recent advances in understanding the role of hypoxia in cellular senescence. The effects of HIFs, immune evasion, PARP-1, gut microbiota, and exosomal mRNA in hypoxia-mediated cell senescence are specifically discussed. This review increases our understanding of the mechanism of hypoxia-mediated cellular senescence and provides new clues for anti-aging processes and the treatment of aging-related diseases. © 2023 The Authors

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/GA20-22037S" target="_blank" >GA20-22037S: The therapeutic potential of novel mTOR inhibitors within the process of ageing</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Pharmacological Research

ISSN

1043-6618

e-ISSN

1096-1186

Volume of the periodical

194

Issue of the periodical within the volume

August

Country of publishing house

GB - UNITED KINGDOM

Number of pages

17

Pages from-to

"Article number: 106841"

UT code for WoS article

001037777100001

EID of the result in the Scopus database

2-s2.0-85163988210