Cell Culture

Aging (Aging-US)

Aging-US published this trending editorial on July 19, 2022 in Volume 14, Issue 14, entitled, "Restoring rhythm to prevent age-related fractures” by researchers Annelies E. Smit, Maaike Schilperoort, and Elizabeth M. Winter from the Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.

DOI - https://doi.org/10.18632/aging.204192 (PDF Download)

Corresponding author - Elizabeth M. Winter - e.m.winter@lumc.nl

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Keywords - aging, circadian rhythm, fractures, osteoporosis, glucocorticoids, chronotherapy

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

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Trending With Impact: Restoring Rhythm to Prevent Age-related Fractures

Aging-US published this research paper on July 5, 2022 in Volume 14, Issue 14, entitled, "Common electrocardiogram measures are not associated with telomere length" by researchers Department of Cardiology, University Hospital, LMU Munich, Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute for Medical Information Processing, Biometry and Epidemiology, Medical Faculty, LMU Munich, Munich, Germany; Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, Mainz, Germany; Pettenkofer School of Public Health Munich, Institute for Medical Information Processing, Biometry and Epidemiology, Medical Faculty, LMU Munich, Munich, Germany.

DOI - https://doi.org/10.18632/aging.204149

Corresponding author - Moritz F. Sinner - moritz.sinner@med.uni-muenchen.de

Abstract

Aims: Aging is accompanied by telomere shortening. Increased telomere shortening is considered a marker of premature aging. Cardiac aging results in the development of cardiac pathologies. Electrocardiogram (ECG) measures reflect cardiac excitation, conduction, and repolarization. ECG measures also prolong with aging and are associated with cardiac pathologies including atrial fibrillation. As premature prolongation of ECG measures is observed, we hypothesized that such prolongation may be associated with telomere length.

Methods and Results: We studied the large, community-based KORA F4 Study. Of 3,080 participants enrolled between 2006 and 2007 with detailed information on demographic, anthropometric, clinical, and ECG characteristics, 2,575 presented with available data on leukocyte telomere length. Telomere length was determined by real-time quantitative PCR and expressed relative to a single copy gene. We fitted multivariable adjusted linear regression models to associate the ECG measures RR-interval, PR-interval, QRS-duration, and heart rate corrected QTc with telomere length.

In our cohort, the mean age was 54.9±12.9 years and 46.6% were men. Increased age was associated with shorter telomere length (p<0.01), and men had shorter telomere length than women (p<0.05). In unadjusted models, heart rate (p=0.023), PR-interval (p<0.01), and QTc-interval (p<0.01) were significantly associated with shorter telomere length. However, no significant associations remained after accounting for age, sex, and covariates.

Conclusions: ECG measures are age-dependent, but not associated with shortened telomere length as a marker of biological aging. Further research is warranted to clarify if shortened telomeres are associated with clinical cardiac pathologies including atrial fibrillation.

Keywords - aging, electrocardiogram, telomere length, cardiac aging

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/agingus​
LinkedIn - https://www.linkedin.com/company/aging/
Pinterest - https://www.pinterest.com/AgingUS/

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Paper Spotlight: Common ECG Measures are not Associated with Telomere Length

Oncotarget

Oncotarget published this research paper on July 28, 2022 in Volume 13, entitled, "Diverse geroprotectors differently affect a mechanism linking cellular aging to cellular quiescence in budding yeast" by researchers from the Department of Biology, Concordia University, Montreal, Quebec H4B 1R6, Canada.

DOI - https://doi.org/10.18632/oncotarget.28256

Correspondence to - Vladimir I. Titorenko - vladimir.titorenko@concordia.ca

Abstract

We propose a hypothesis of a mechanism linking cellular aging to cellular quiescence in chronologically aging budding yeast. Our hypothesis posits that this mechanism integrates four different processes, all of which are initiated after yeast cells cultured in a medium initially containing glucose consume it. Quiescent cells that develop in these cultures can be separated into the high- and low-density sub-populations of different buoyant densities. Process 1 of the proposed mechanism consists of a cell-cycle arrest in the G1 phase and leads to the formation of high-density quiescent cells. Process 2 results in converting high-density quiescent cells into low-density quiescent cells. Processes 3 and 4 cause a fast or slow decline in the quiescence of low- or high-density quiescent cells, respectively. Here, we tested our hypothesis by assessing how four different geroprotectors influence the four processes that could link cellular aging to cellular quiescence. We found that these geroprotectors differently affect processes 1 and 2 and decelerate processes 3 and 4. We also found that a rise in trehalose within quiescent yeast contributes to chronological aging and quiescence maintenance. These data collectively provide conclusive evidence for a mechanistic link between cellular aging and cellular quiescence.

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Keywords - cellular aging, cellular quiescence, longevity, gerotargets, geroprotectors

About Oncotarget

Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Diverse Geroprotectors Differently Affect Mechanism Linking Cellular Aging to Cellular Quiescence in Budding Yeast

Oncotarget published this trending research paper on July 19, 2022 in Volume 13, entitled, "CUDC907, a dual phosphoinositide-3 kinase/histone deacetylase inhibitor, promotes apoptosis of NF2 Schwannoma cells" by researchers from the Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL; Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL; Department of Pathology, University of Miami Miller School of Medicine, Miami, FL; Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL.

DOI - https://doi.org/10.18632/oncotarget.28254

Correspondence to - Cristina Fernandez-Valle - cfv@ucf.edu

Abstract

Neurofibromatosis Type 2 (NF2) is a rare tumor disorder caused by pathogenic variants of the merlin tumor suppressor encoded by NF2. Patients develop vestibular schwannomas (VS), peripheral schwannomas, meningiomas, and ependymomas. There are no approved drug therapies for NF2. Previous work identified phosphoinositide-3 kinase (PI3K) as a druggable target. Here we screened PI3K pathway inhibitors for efficacy in reducing viability of human schwannoma cells. The lead compound, CUDC907, a dual histone deacetylase (HDAC)/PI3K inhibitor, was further evaluated for its effects on isolated and nerve-grafted schwannoma model cells, and primary VS cells. CUDC907 (3 nM IG50) reduced human merlin deficient Schwann cell (MD-SC) viability and was 5–100 fold selective for MD over WT-SCs. CUDC907 (10 nM) promoted cell cycle arrest and caspase-3/7 activation within 24 h in human MD-SCs. Western blots confirmed a dose-dependent increase in acetylated lysine and decreases in pAKT and YAP. CUDC907 decreased tumor growth rate by 44% in a 14-day treatment regimen, modulated phospho-target levels, and decreased YAP levels. In five primary VS, CUDC907 decreased viability, induced caspase-3/7 cleavage, and reduced YAP levels. Its efficacy correlated with basal phospho-HDAC2 levels. CUDC907 has cytotoxic activity in NF2 schwannoma models and primary VS cells and is a candidate for clinical trials.

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Press release - https://www.oncotarget.com/news/pr/oncotarget-cudc-promotes-apoptosis-of-nf-schwannoma-cells/

Keywords - fimepinostat, Schwann cell, vestibular schwanomma, merlin, nerve allograft

About Oncotarget

Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Trending With Impact: CUDC907 Promotes Apoptosis of NF2 Schwannoma Cells

CD Genomics

RNA-Seq is the premier tool for mapping and quantifying transcriptomes by utilizing next-generation sequencing (NGS) technology. The transcriptome refers to the complete set of transcripts in a cell, which provides information on the transcript level for a specific developmental stage or physiological condition. Understanding the transcriptome is necessary for interpreting the functional elements of the genome and understanding development and disease. The key purpose of transcriptomics includes cataloging all species of transcripts; determining the transcriptional structure of genes; and quantifying the expression levels of each transcript under different conditions.

The Development and Workflow of RNA-seq, Learn more at https://www.cd-genomics.com/resourse-Bioinformatics-Workflow-of-RNA-Seq.html

Principle and Workflow of RNA Sequencing

Oncotarget published this trending research paper on February 14, 2022 in Volume 13, entitled, "Telomere shortening accelerates tumor initiation in the L2-IL1B mouse model of Barrett esophagus and emerges as a possible biomarker" by researchers from II Medizinische Klinik, Technische Universität München, Munich, Germany; Department of Medicine, Columbia University Irving Medical Center, New York, NY; Klinik für Innere Medizin II, Universitätsklinikum Freiburg, Freiburg, Germany.

DOI - https://doi.org/10.18632/oncotarget.28198

Correspondence to - Michael Quante - michael.quante@uniklinik-freiburg.de

Abstract

Barrett’s esophagus (BE) is a precursor of the esophageal adenocarcinoma (EAC). BE- development and its progression to cancer is associated with gastroesophageal reflux disease. However, there is currently no molecular risk prediction model that accurately identifies patients at high risk for EAC. Here, we investigated the impact of shortened telomeres in a mouse model for Barrett esophagus (L2-IL1B). The L2-IL1B mouse model is characterized by IL-1β-mediated inflammation, which leads to a Barrett-like metaplasia in the transition zone between the squamous forestomach and glandular cardia/stomach. Telomere shortening was achieved by mTERC knockout. In the second generation (G2) of mTERC knockout L2-IL1B.mTERC−/− G2 mice exhibited telomere dysfunction with significantly shorter telomeres as measured by qFISH compared to L2-IL1B mice, correlating with stronger DNA damage in the form of phosphorylation of H2AX (γH2AX). Macroscopically, tumor area along the squamocolumnar junction (SCJ) was increased in L2-IL1B.mTERC−/− G2 mice, along with increased histopathological dysplasia. In vitro studies indicated increased organoid formation capacity in BE tissue from L2-IL1B.mTERC−/− G2 mice. In addition, pilot studies of human BE-, dysplasia- and EAC tissue samples confirmed that BE epithelial cells with or without dysplasia (LGD) had shorter telomeres compared to gastric cardia tissue. Of note, differentiated goblet cells retained longer telomeres than columnar lined BE epithelium. In conclusion, our studies suggest that shortened telomeres are functionally important for tumor development in a mouse model of BE and are associated with proliferating columnar epithelium in human BE. We propose that shortened telomeres should be evaluated further as a possible biomarker of cancer risk in BE patients.

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Keywords - Barrett's esophagus, telomere shortening, esophageal cancer, risk factor, TERT/TERC

About Oncotarget

Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com

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Trending With Impact: Telomere Shortening in Barrett's Esophagus

Oncotarget published this trending research paper on July 2, 2022 in Volume 13, entitled, "Continuous treatment with abemaciclib leads to sustained and efficient inhibition of breast cancer cell proliferation" by researchers from Discovery Chemistry Research and Technology, Eli Lilly and Company, Madrid, Spain; Eli Lilly and Company, Indianapolis, IN; Eli Lilly and Company, New York, NY.

DOI - https://doi.org/10.18632/oncotarget.28249

Correspondence to - María José Lallena - lallena_maria_jose@lilly.com

Abstract

Abemaciclib is an oral, selective cyclin-dependent kinase 4 & 6 inhibitor (CDK4 & 6i), approved for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) as monotherapy for endocrine refractory disease, and with endocrine therapy (ET) for initial treatment and after progression on ET. Abemaciclib has also shown clinical activity in combination with ET in patients with high risk early BC (EBC). Here, we examined the preclinical attributes of abemaciclib and other CDK4 & 6i using biochemical and cell-based assays. In vitro, abemaciclib preferentially inhibited CDK4 kinase activity versus CDK6, resulting in inhibition of cell proliferation in a panel of BC cell lines with higher average potency than palbociclib or ribociclib. Abemaciclib showed activity regardless of HER2 amplification and phosphatidylinositol 3-kinase (PI3KCA) gene mutation status. In human bone marrow progenitor cells, abemaciclib showed lower impact on myeloid maturation than other CDK4 & 6i when tested at unbound concentrations similar to those observed in clinical trials. Continuous abemaciclib treatment provided profound inhibition of cell proliferation, and triggered senescence and apoptosis. These preclinical results support the unique efficacy and safety profile of abemaciclib observed in clinical trials.

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Press release - https://www.oncotarget.com/news/pr/oncotarget-continuous-treatment-with-abemaciclib-leads-to-sustained-and-efficient-inhibition-of-breast-cancer-cell-proliferation/

Keywords - abemaciclib, breast cancer, cell lines, CDK4/6, continuous dosing

About Oncotarget

Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com

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Paper Abstract: Continuous Abemaciclib Treatment Leads to Breast Cancer Inhibition

CD Genomics has extensive experience in providing support for the selection and design of microsatellite markers for a wide range of plant and animal species. Besides microsatellite genotyping, we also provide genotyping by sequencing (GBS) method, which saves time and resources.  https://www.cd-genomics.com/Microsatellite-Genotyping-Service.html

Microsatellite Genotyping Service  at CD Genomics

Teach Me in 10

3D cell culture systems are gaining interest in the scientific community as they provide more physiologically relevant information and more predictive in vivo data. For more than 25 years, Corning Life Sciences has delivered innovative educational tools and protocols that have advanced the science of 3D cell culture and supported the widespread adoption of these models.

In this Teach Me In 10 episode one of Corning’s customers, Dr. Joseph Regan, shares information from a recently published protocol for the isolation and functional validation of label-retaining quiescent colorectal cancer stem cells from patient-derived organoids for RNA-seq.

Cell Culture

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