scholarly journals nc886, a Non-Coding RNA, Is a New Biomarker and Epigenetic Mediator of Cellular Senescence in Fibroblasts

2021 ◽  
Vol 22 (24) ◽  
pp. 13673
Author(s):  
Yuna Kim ◽  
Hyanggi Ji ◽  
Eunae Cho ◽  
Nok-Hyun Park ◽  
Kyeonghwan Hwang ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Replicative Senescence ◽  
Tumor Formation ◽  
Epigenetic Changes ◽  
Functional Studies ◽  
Human Models ◽  
Age Related ◽  
Non Coding Rna ◽  
Epigenetic Regulators

Functional studies of organisms and human models have revealed that epigenetic changes can significantly impact the process of aging. Non-coding RNA (ncRNA), one of epigenetic regulators, plays an important role in modifying the expression of mRNAs and their proteins. It can mediate the phenotype of cells. It has been reported that nc886 (=vtRNA2-1 or pre-miR-886), a long ncRNA, can suppress tumor formation and photo-damages of keratinocytes caused by UVB. The aim of this study was to determine the role of nc886 in replicative senescence of fibroblasts and determine whether substances capable of controlling nc886 expression could regulate cellular senescence. In replicative senescence fibroblasts, nc886 expression was decreased while methylated nc886 was increased. There were changes of senescence biomarkers including SA-β-gal activity and expression of p16INK4A and p21Waf1/Cip1 in senescent cells. These findings indicate that the decrease of nc886 associated with aging is related to cellular senescence of fibroblasts and that increasing nc886 expression has potential to suppress cellular senescence. AbsoluTea Concentrate 2.0 (ATC) increased nc886 expression and ameliorated cellular senescence of fibroblasts by inhibiting age-related biomarkers. These results indicate that nc886 has potential as a new target for anti-aging and that ATC can be a potent epigenetic anti-aging ingredient.

scholarly journals Targeting Epigenetic Regulators for Endometrial Cancer Therapy: Its Molecular Biology and Potential Clinical Applications

2021 ◽  
Vol 22 (5) ◽  
pp. 2305
Author(s):  
Futaba Inoue ◽  
Kenbun Sone ◽  
Yusuke Toyohara ◽  
Yu Takahashi ◽  
Asako Kukita ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Endometrial Cancer ◽  
Histone Modification ◽  
Treatment Options ◽  
Diagnostic Tools ◽  
Epigenetic Changes ◽  
Non Coding Rna ◽  
Advanced Stages ◽  
Epigenetic Regulators

Endometrial cancer is one of the most frequently diagnosed gynecological malignancies worldwide. However, its prognosis in advanced stages is poor, and there are only few available treatment options when it recurs. Epigenetic changes in gene function, such as DNA methylation, histone modification, and non-coding RNA, have been studied for the last two decades. Epigenetic dysregulation is often reported in the development and progression of various cancers. Recently, epigenetic changes in endometrial cancer have also been discussed. In this review, we give the main points of the role of DNA methylation and histone modification in endometrial cancer, the diagnostic tools to determine these modifications, and inhibitors targeting epigenetic regulators that are currently in preclinical studies and clinical trials.

scholarly journals SENEBLOC, a long non-coding RNA suppresses senescence via p53-dependent and independent mechanisms

2020 ◽  
Vol 48 (6) ◽  
pp. 3089-3102 ◽  
Author(s):  
Cheng Lin Xu ◽  
Ben Sang ◽  
Guang Zhi Liu ◽  
Jin Ming Li ◽  
Xu Dong Zhang ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Replicative Senescence ◽  
Gene Promoter ◽  
Epigenetic Silencing ◽  
Transformed Cells ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Abstract Long non-coding RNAs (lncRNAs) have emerged as important biological tuners. Here, we reveal the role of an uncharacterized lncRNA we call SENEBLOC that is expressed by both normal and transformed cells under homeostatic conditions. SENEBLOC was shown to block the induction of cellular senescence through dual mechanisms that converge to repress the expression of p21. SENEBLOC facilitates the association of p53 with MDM2 by acting as a scaffold to promote p53 turnover and decrease p21 transactivation. Alternatively, SENEBLOC was shown to affect epigenetic silencing of the p21 gene promoter through regulation of HDAC5. Thus SENEBLOC drives both p53-dependent and p53-independent mechanisms that contribute to p21 repression. Moreover, SENEBLOC was shown to be involved in both oncogenic and replicative senescence, and from the perspective of senolytic agents we show that the antagonistic actions of rapamycin on senescence are dependent on SENEBLOC expression.

scholarly journals Role of Age-Related Mitochondrial Dysfunction in Sarcopenia

2020 ◽  
Vol 21 (15) ◽  
pp. 5236 ◽  
Author(s):  
Evelyn Ferri ◽  
Emanuele Marzetti ◽  
Riccardo Calvani ◽  
Anna Picca ◽  
Matteo Cesari ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cellular Senescence ◽  
Significant Loss ◽  
Muscle Aging ◽  
Age Related ◽  
Mitochondrial Functions ◽  
Health Quality ◽  
Skeletal Muscle Aging ◽  
And Function

Skeletal muscle aging is associated with a significant loss of skeletal muscle strength and power (i.e., dynapenia), muscle mass and quality of life, a phenomenon known as sarcopenia. This condition affects nearly one-third of the older population and is one of the main factors leading to negative health outcomes in geriatric patients. Notwithstanding the exact mechanisms responsible for sarcopenia are not fully understood, mitochondria have emerged as one of the central regulators of sarcopenia. In fact, there is a wide consensus on the assumption that the loss of mitochondrial integrity in myocytes is the main factor leading to muscle degeneration. Mitochondria are also key players in senescence. It has been largely proven that the modulation of mitochondrial functions can induce the death of senescent cells and that removal of senescent cells improves musculoskeletal health, quality, and function. In this review, the crosstalk among mitochondria, cellular senescence, and sarcopenia will be discussed with the aim to elucidate the role that the musculoskeletal cellular senescence may play in the onset of sarcopenia through the mediation of mitochondria.

scholarly journals What have we learned from basic science studies on idiopathic pulmonary fibrosis?

2019 ◽  
Vol 28 (153) ◽  
pp. 190029 ◽  
Author(s):  
Toyoshi Yanagihara ◽  
Seidai Sato ◽  
Chandak Upagupta ◽  
Martin Kolb
Keyword(s):  
Extracellular Matrix ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cellular Senescence ◽  
Basic Science ◽  
Science Studies ◽  
Cell Types ◽  
Age Related ◽  
Tremendous Progress

Idiopathic pulmonary fibrosis is a fatal age-related lung disease characterised by progressive and irreversible scarring of the lung. Although the details are not fully understood, there has been tremendous progress in understanding the pathogenesis of idiopathic pulmonary fibrosis, which has led to the identification of many new potential therapeutic targets. In this review we discuss several of these advances with a focus on genetic susceptibility and cellular senescence primarily affecting epithelial cells, activation of profibrotic pathways, disease-enhancing fibrogenic cell types and the role of the remodelled extracellular matrix.

scholarly journals Senescence and Cancer: Role of Nitric Oxide (NO) in SASP

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1145
Author(s):  
Nesrine Mabrouk ◽  
Silvia Ghione ◽  
Véronique Laurens ◽  
Stéphanie Plenchette ◽  
Ali Bettaieb ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cancer Treatment ◽  
Cellular Senescence ◽  
Negative Effects ◽  
No Donors ◽  
Cell State ◽  
Age Related ◽  
A Cell ◽  
Secretory Phenotype

Cellular senescence is a cell state involved in both physiological and pathological processes such as age-related diseases and cancer. While the mechanism of senescence is now well known, its role in tumorigenesis still remains very controversial. The positive and negative effects of senescence on tumorigenesis depend largely on the diversity of the senescent phenotypes and, more precisely, on the senescence-associated secretory phenotype (SASP). In this review, we discuss the modulatory effect of nitric oxide (NO) in SASP and the possible benefits of the use of NO donors or iNOS inducers in combination with senotherapy in cancer treatment.

scholarly journals DNA damage responses in ageing

Open Biology ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 190168 ◽  
Author(s):  
Paulo F. L. da Silva ◽  
Björn Schumacher
Keyword(s):  
Dna Damage ◽  
Stress Response ◽  
Cellular Senescence ◽  
Damage Accumulation ◽  
Genome Instability ◽  
Age Related ◽  
Progeroid Syndromes ◽  
Dna Damage Responses ◽  
Universal Feature

Ageing appears to be a nearly universal feature of life, ranging from unicellular microorganisms to humans. Longevity depends on the maintenance of cellular functionality, and an organism's ability to respond to stress has been linked to functional maintenance and longevity. Stress response pathways might indeed become therapeutic targets of therapies aimed at extending the healthy lifespan. Various progeroid syndromes have been linked to genome instability, indicating an important causal role of DNA damage accumulation in the ageing process and the development of age-related pathologies. Recently, non-cell-autonomous mechanisms including the systemic consequences of cellular senescence have been implicated in regulating organismal ageing. We discuss here the role of cellular and systemic mechanisms of ageing and their role in ageing-associated diseases.

scholarly journals The role of microRNAs in cellular senescence and age-related conditions of cartilage and bone

2014 ◽  
Vol 86 (1) ◽  
pp. 92-99 ◽  
Author(s):  
Sylvia Weilner ◽  
Regina Grillari-Voglauer ◽  
Heinz Redl ◽  
Johannes Grillari ◽  
Thomas Nau
Keyword(s):  
Cellular Senescence ◽  
Age Related

scholarly journals Ageing, Cellular Senescence and Neurodegenerative Disease

2018 ◽  
Vol 19 (10) ◽  
pp. 2937 ◽  
Author(s):  
Marios Kritsilis ◽  
Sophia V. Rizou ◽  
Paraskevi Koutsoudaki ◽  
Konstantinos Evangelou ◽  
Vassilis Gorgoulis ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neurodegenerative Disease ◽  
Cellular Senescence ◽  
Biological Process ◽  
The Novel ◽  
Cell Type ◽  
Age Related ◽  
Cell Type Specific ◽  
First Time

Ageing is a major risk factor for developing many neurodegenerative diseases. Cellular senescence is a homeostatic biological process that has a key role in driving ageing. There is evidence that senescent cells accumulate in the nervous system with ageing and neurodegenerative disease and may predispose a person to the appearance of a neurodegenerative condition or may aggravate its course. Research into senescence has long been hindered by its variable and cell-type specific features and the lack of a universal marker to unequivocally detect senescent cells. Recent advances in senescence markers and genetically modified animal models have boosted our knowledge on the role of cellular senescence in ageing and age-related disease. The aim now is to fully elucidate its role in neurodegeneration in order to efficiently and safely exploit cellular senescence as a therapeutic target. Here, we review evidence of cellular senescence in neurons and glial cells and we discuss its putative role in Alzheimer’s disease, Parkinson’s disease and multiple sclerosis and we provide, for the first time, evidence of senescence in neurons and glia in multiple sclerosis, using the novel GL13 lipofuscin stain as a marker of cellular senescence.

scholarly journals Aging Induces Profound Changes in sncRNA in Rat Sperm and These Changes Are Modified by Perinatal Exposure to Environmental Flame Retardant

2020 ◽  
Vol 21 (21) ◽  
pp. 8252
Author(s):  
Alexander Suvorov ◽  
J. Richard Pilsner ◽  
Vladimir Naumov ◽  
Victoria Shtratnikova ◽  
Anna Zheludkevich ◽  
...  
Keyword(s):  
Age Groups ◽  
Natural Aging ◽  
Paternal Age ◽  
Differentially Expressed ◽  
Epigenetic Changes ◽  
Protein Coding ◽  
False Discovery ◽  
Age Related ◽  
Non Coding Rna ◽  
Environmental Xenobiotic

Advanced paternal age at fertilization is a risk factor for multiple disorders in offspring and may be linked to age-related epigenetic changes in the father’s sperm. An understanding of aging-related epigenetic changes in sperm and environmental factors that modify such changes is needed. Here, we characterize changes in sperm small non-coding RNA (sncRNA) between young pubertal and mature rats. We also analyze the modification of these changes by exposure to environmental xenobiotic 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47). sncRNA libraries prepared from epididymal spermatozoa were sequenced and analyzed using DESeq 2. The distribution of small RNA fractions changed with age, with fractions mapping to rRNA and lncRNA decreasing and fractions mapping to tRNA and miRNA increasing. In total, 249 miRNA, 908 piRNA and 227 tRNA-derived RNA were differentially expressed (twofold change, false discovery rate (FDR) p ≤ 0.05) between age groups in control animals. Differentially expressed miRNA and piRNA were enriched for protein-coding targets involved in development and metabolism, while piRNA were enriched for long terminal repeat (LTR) targets. BDE-47 accelerated age-dependent changes in sncRNA in younger animals, decelerated these changes in older animals and increased the variance in expression of all sncRNA. Our results indicate that the natural aging process has profound effects on sperm sncRNA profiles and this effect may be modified by environmental exposure.

scholarly journals LncRNA NEAT1 remodels chromatin to promote the 5-Fu resistance by maintaining colorectal cancer stemness

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Yihao Zhu ◽  
Hanqing Hu ◽  
Ziming Yuan ◽  
Qian Zhang ◽  
Huan Xiong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chromatin Remodeling ◽  
Chromatin Immunoprecipitation ◽  
Cancer Stemness ◽  
Functional Studies ◽  
Non Coding Rna ◽  
New Strategy ◽  
Lncrna Neat1 ◽  
Long Non Coding Rna

Abstract Resistance of chemotherapy is one of causes of recurrence and poor prognosis in patients with colorectal cancer (CRC). The role of differentially expressed long non-coding RNA (lncRNA) in 5-fluorouracil (5-Fu) resistance has not been fully elucidated. Here we observed that lncRNA NEAT1 was associated with 5-Fu resistance in CRC. Our Functional studies showed that NEAT1 promoted 5-Fu resistance in colorectal cells. In addition, A-TAC sequencing and chromatin immunoprecipitation (ChIP) showed that NEAT1 affected chromatin remodeling, increased the acetylation levels of histones, increased their enrichment at the promoters of ALDH1 and c-Myc, and promoted the expression of ALDH1 and c-Myc. Taken together, our study suggested that NEAT1 promoted 5-Fu resistance and cancer stemness by remodeling chromatin. Our finding provides a novel role of NEAT1 and may provide a new strategy for the treatment of CRC 5-Fu resistance.

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