Nutrition, Oxidative Damage, Telomere Shortening, and Cellular Senescence: Individual or Connected Agents of Aging?

2000 ◽  
Vol 71 (1-2) ◽  
pp. 32-42 ◽  
Author(s):  
Bridget J. Jennings ◽  
Susan E. Ozanne ◽  
C.Nicholas Hales
Keyword(s):  
Oxidative Damage ◽  
Cellular Senescence ◽  
Telomere Shortening

scholarly journals Obstructive Sleep Apnea as an Acceleration Trigger of Cellular Senescence Processes through Telomere Shortening

2021 ◽  
Vol 22 (22) ◽  
pp. 12536
Author(s):  
Szymon Turkiewicz ◽  
Marta Ditmer ◽  
Marcin Sochal ◽  
Piotr Białasiewicz ◽  
Dominik Strzelecki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Circadian Clock ◽  
Chronic Inflammation ◽  
Cellular Senescence ◽  
Molecular Mechanisms ◽  
Telomere Shortening ◽  
Age Related ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) is chronic disorder which is characterized by recurrent pauses of breathing during sleep which leads to hypoxia and its two main pathological sequelae: oxidative stress and chronic inflammation. Both are also associated with cellular senescence. As OSA patients present with higher prevalence of age-related disorders, such as atrial hypertension or diabetes mellitus type 2, a relationship between OSA and accelerated aging is observable. Furthermore, it has been established that these OSA are associated with telomere shortening. This process in OSA is likely caused by increased oxidative DNA damage due to increased reactive oxygen species levels, DNA repair disruptions, hypoxia, chronic inflammation, and circadian clock disturbances. The aim of the review is to summarize study outcomes on changes in leukocyte telomere length (LTL) in OSA patients and describe possible molecular mechanisms which connect cellular senescence and the pathophysiology of OSA. The majority of OSA patients are characterized by LTL attrition due to oxidative stress, hypoxia and inflammation, which make a kind of positive feedback loop, and circadian clock disturbance.

scholarly journals Roles for the 8-Oxoguanine DNA Repair System in Protecting Telomeres From Oxidative Stress

2021 ◽  
Vol 9 ◽  
Author(s):  
Mariarosaria De Rosa ◽  
Samuel A. Johnson ◽  
Patricia L. Opresko
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Genome Stability ◽  
Repair System ◽  
Telomeric Dna ◽  
Telomere Shortening ◽  
Guanine Oxidation ◽  
Repeat Sequences ◽  
Human Reproductive ◽  
Base Lesion

Telomeres are protective nucleoprotein structures that cap linear chromosome ends and safeguard genome stability. Progressive telomere shortening at each somatic cell division eventually leads to critically short and dysfunctional telomeres, which can contribute to either cellular senescence and aging, or tumorigenesis. Human reproductive cells, some stem cells, and most cancer cells, express the enzyme telomerase to restore telomeric DNA. Numerous studies have shown that oxidative stress caused by excess reactive oxygen species is associated with accelerated telomere shortening and dysfunction. Telomeric repeat sequences are remarkably susceptible to oxidative damage and are preferred sites for the production of the mutagenic base lesion 8-oxoguanine, which can alter telomere length homeostasis and integrity. Therefore, knowledge of the repair pathways involved in the processing of 8-oxoguanine at telomeres is important for advancing understanding of the pathogenesis of degenerative diseases and cancer associated with telomere instability. The highly conserved guanine oxidation (GO) system involves three specialized enzymes that initiate distinct pathways to specifically mitigate the adverse effects of 8-oxoguanine. Here we introduce the GO system and review the studies focused on investigating how telomeric 8-oxoguanine processing affects telomere integrity and overall genome stability. We also discuss newly developed technologies that target oxidative damage selectively to telomeres to investigate roles for the GO system in telomere stability.

scholarly journals Ginger Extract Promotes Telomere Shortening and Cellular Senescence in A549 Lung Cancer Cells

ACS Omega ◽  
2018 ◽  
Vol 3 (12) ◽  
pp. 18572-18581
Author(s):  
Navakoon Kaewtunjai ◽  
Rawiwan Wongpoomchai ◽  
Arisa Imsumran ◽  
Wilart Pompimon ◽  
Anan Athipornchai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cellular Senescence ◽  
Lung Cancer Cells ◽  
Ginger Extract ◽  
Telomere Shortening ◽  
A549 Lung

scholarly journals MICRORNA REGULATORS OF THE SENESCENCE TRANSCRIPTOME

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S835-S835
Author(s):  
O’Wayne Rodney ◽  
Myriam Gorospe ◽  
Kotb Abdelmohsen
Keyword(s):  
Dna Damage ◽  
Cellular Senescence ◽  
Growth Arrest ◽  
Proliferating Cells ◽  
Telomere Shortening ◽  
Qpcr Analysis ◽  
Oncogene Activation ◽  
Dna Foci ◽  
Transcriptome Signature

Abstract Cellular senescence is a state of indefinite growth arrest triggered in response to sublethal stresses such as telomere shortening, DNA damage, oxidative injury, oncogene activation, and hypoxia. Compared with proliferating cells, senescent cells are enlarged, display heterochromatic DNA foci, and express distinct subsets of proteins, including the enzyme β-galactosidase (β-gal). Previously, we identified transcriptome signature of senescent cells. We asked if these transcripts might be regulated by microRNAs (miRNAs). To address this question, we identified six miRNAs (miR-129-5p, -19a-3p, -128-3p, -124-3p, -340-5p, and -27b-3p) as potential regulators of subsets of transcripts differentially expressed during senescence. RT-qPCR analysis indicated that miR-129-5p, -19a-3p, -128-3p, -124-3p, and -340-5p were downregulated in senescent cells. We modulated these miRNAs in proliferating WI-38 fibroblasts and found that miRNA antagomirs did not show significant changes in β-gal activity. Interestingly, however, overexpression of miR-124-3p or miR-340-5p increased β-gal activity. We conclude that despite the decrease of miR-124-3p and miR-340-5p in senescent cells, their overexpression enhanced senescence as indicated by β-gal activity. Future analyses will focus on the mechanisms through which these miRNAs induce senescence and their physiologic and pathologic impacts in vivo.

scholarly journals Cellular Senescence: Many Roads, One Final Destination

2010 ◽  
Vol 10 ◽  
pp. 727-741 ◽  
Author(s):  
Raya Saab
Keyword(s):  
Tumor Suppressor ◽  
Cellular Senescence ◽  
Short Review ◽  
Premalignant Lesions ◽  
Telomere Shortening ◽  
Final Destination ◽  
Suppressor Mechanism ◽  
Oncogenic Stress

Cellular senescence is a tumor-suppressor mechanism that has been shown to occur in response to multiple signals, including oncogenic stress, DNA damage, oxidative stress, telomere shortening, and other tumor-promoting insults. Over the past decade, much has been uncovered regarding the phenotype of this tumor-suppressor response and the underlying pathways necessary for its establishment. However, we have also learned that the intricate details of signaling pathways underlying senescence as a tumor-suppressor response are very much context dependent. In addition, cross-talk among pathways, and negative and positive feedback loops, all complicate our understanding of this process. This short review attempts to summarize what is known to date regarding senescence in tumor suppression, bothin vitroandin vivo. Further insights into pathways necessary for senescence will hopefully identify appropriate targets for interventions to not only induce senescence as a treatment of cancerous lesions, but also to maintain this state in premalignant lesions in an effort to prevent progression to cancer.

scholarly journals Dysfunctional telomeres trigger cellular senescence mediated by cyclic GMP-AMP synthase

2020 ◽  
Vol 295 (32) ◽  
pp. 11144-11160 ◽  
Author(s):  
Salim Abdisalaam ◽  
Souparno Bhattacharya ◽  
Shibani Mukherjee ◽  
Debapriya Sinha ◽  
Kalayarasan Srinivasan ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Cyclic Gmp ◽  
Imaging Techniques ◽  
Common Mechanism ◽  
Premature Senescence ◽  
Dna Sensing ◽  
Dna Double Strand Breaks ◽  
Telomere Shortening ◽  
Strand Breaks ◽  
Senescence Phenotype

Defective DNA damage response (DDR) signaling is a common mechanism that initiates and maintains the cellular senescence phenotype. Dysfunctional telomeres activate DDR signaling, genomic instability, and cellular senescence, but the links among these events remains unclear. Here, using an array of biochemical and imaging techniques, including a highly regulatable CRISPR/Cas9 strategy to induce DNA double strand breaks specifically in the telomeres, ChIP, telomere immunofluorescence, fluorescence in situ hybridization (FISH), micronuclei imaging, and the telomere shortest length assay (TeSLA), we show that chromosome mis-segregation due to imperfect DDR signaling in response to dysfunctional telomeres creates a preponderance of chromatin fragments in the cytosol, which leads to a premature senescence phenotype. We found that this phenomenon is caused not by telomere shortening, but by cyclic GMP–AMP synthase (cGAS) recognizing cytosolic chromatin fragments and then activating the stimulator of interferon genes (STING) cytosolic DNA-sensing pathway and downstream interferon signaling. Significantly, genetic and pharmacological manipulation of cGAS not only attenuated immune signaling, but also prevented premature cellular senescence in response to dysfunctional telomeres. The findings of our study uncover a cellular intrinsic mechanism involving the cGAS-mediated cytosolic self-DNA–sensing pathway that initiates premature senescence independently of telomere shortening.

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