Cell Culture

Aging (Aging-US)

Aging (Aging-US) published this priority research paper as the cover for Volume 14, Issue 1, entitled, "Reduced growth rate of aged muscle stem cells is associated with impaired mechanosensitivity" by researchers from the Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam 1081 HZ, The Netherlands; Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam 1081 LA, The Netherlands; Sorbonne Université, INSERM UMRS974, Center for Research in Myology, Paris 75013, France; Department of Physiology, Amsterdam University Medical Center VUmc, Amsterdam Cardiovascular Sciences, Amsterdam 1081 HZ, The Netherlands; Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve 1348, Belgium; Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Leuven 3001, Belgium; Faculty of Medicine and Pharmacy, NeuroMyoGène UCBL-CNRS UMR 5310, INSERM U1217, Lyon 69008, France.

DOI - https://doi.org/10.18632/aging.203830

Correspondence to - Richard T. Jaspers - r.t.jaspers@vu.nl

Abstract:
Aging-associated muscle wasting and impaired regeneration are caused by deficiencies in muscle stem cell (MuSC) number and function. We postulated that aged MuSCs are intrinsically impaired in their responsiveness to omnipresent mechanical cues through alterations in MuSC morphology, mechanical properties, and number of integrins, culminating in impaired proliferative capacity. Here we show that aged MuSCs exhibited significantly lower growth rate and reduced integrin-α7 expression as well as lower number of phospho-paxillin clusters than young MuSCs. Moreover, aged MuSCs were less firmly attached to matrigel-coated glass substrates compared to young MuSCs, as 43% of the cells detached in response to pulsating fluid shear stress (1 Pa). YAP nuclear localization was 59% higher than in young MuSCs, yet YAP target genes Cyr61 and Ctgf were substantially downregulated. When subjected to pulsating fluid shear stress, aged MuSCs exhibited reduced upregulation of proliferation-related genes. Together these results indicate that aged MuSCs exhibit impaired mechanosensitivity and growth potential, accompanied by altered morphology and mechanical properties as well as reduced integrin-α7 expression. Aging-associated impaired muscle regenerative capacity and muscle wasting is likely due to aging-induced intrinsic MuSC alterations and dysfunctional mechanosensitivity.

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Keywords - aging, mechanosensitivity, muscle stem cell, proliferation, YAP signaling

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 http://www.Aging-US.com​​ or 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/

Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​

Media Contact
18009220957
MEDIA@IMPACTJOURNALS.COM

Impaired Mechanosensitivity in Aged Muscle Stem Cells

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Creative Bioarray

Parallel Artificial Membrane Permeability Assay (PAMPA) is a cell-free permeation model used to predict passive drug transport. Passive diffusion is an important factor in determining the absorption of orally administered compounds in the gastrointestinal tract (GIT), penetration of the blood-brain barrier (BBB), and general transport across cell membranes.

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PAMPA Permeability Assay

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Bivariate Cell Cycle Assay

Oncotarget

Oncotarget’s cover paper this week (Volume 12, Issue 26) is entitled, "Comparative transcriptome analysis between patient and endometrial cancer cell lines to determine common signaling pathways and markers linked to cancer progression," by researchers from the Department of Gynecologic Surgery & Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD; Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD; Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD; National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD; Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD.

Abstract:
The rising incidence and mortality of endometrial cancer (EC) in the United States calls for an improved understanding of the disease's progression. Current methodologies for diagnosis and treatment rely on the use of cell lines as models for tumor biology. However, due to inherent heterogeneity and differential growing environments between cell lines and tumors, these comparative studies have found little parallels in molecular signatures. As a consequence, the development and discovery of preclinical models and reliable drug targets are delayed. In this study, we established transcriptome parallels between cell lines and tumors from The Cancer Genome Atlas (TCGA) with the use of optimized normalization methods. We identified genes and signaling pathways associated with regulating the transformation and progression of EC. Specifically, the LXR/RXR activation, neuroprotective role for THOP1 in Alzheimer’s disease, and glutamate receptor signaling pathways were observed to be mostly downregulated in advanced cancer stage. While some of these highlighted markers and signaling pathways are commonly found in the central nervous system (CNS), our results suggest a novel function of these genes in the periphery. Finally, our study underscores the value of implementing appropriate normalization methods in comparative studies to improve the identification of accurate and reliable markers.


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DOI - https://doi.org/10.18632/oncotarget.28161

Full text - https://www.oncotarget.com/article/28161/text/

Correspondence to - T. John Wu - twu@usuhs.edu

Keywords - endometrial cancer, cancer stage, comparative transcriptome analysis, signaling pathways, normalization

About Oncotarget

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

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

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Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls

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18009220957

A Study on Biomarkers of Endometrial Cancer Progression

Aging (Aging-US) published this trending research paper on July 16, 2020, entitled, "Activation of C-reactive protein proinflammatory phenotype in the blood retinal barrier in vitro: implications for age-related macular degeneration" by researchers from the Group of Ocular Inflammation, Clinical and Experimental Studies, Institut d’Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain; Department of Life Sciences, Manchester Metropolitan University, Manchester, UK; Cardiovascular Research Center-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, CiberCV, Institute Carlos III, Barcelona, Spain; Academic Unit of Ophthalmology, School of Clinical Sciences and School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK; National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London, UK.

Abstract:
The retinal pigment epithelium (RPE) is considered one of the main targets of age-related macular degeneration (AMD), the leading cause of irreversible vision loss among the ageing population worldwide. Persistent low grade inflammation and oxidative stress eventually lead to RPE dysfunction and disruption of the outer blood-retinal barrier (oBRB). Increased levels of circulating pentameric C-reactive protein (pCRP) are associated with higher risk of AMD. The monomeric form (mCRP) has been detected in drusen, the hallmark deposits associated with AMD, and we have found that mCRP induces oBRB disruption. However, it is unknown how mCRP is generated in the subretinal space. Using a Transwell model we found that both pCRP and mCRP can cross choroidal endothelial cells and reach the RPE in vitro and that mCRP, but not pCRP, is able to cross the RPE monolayer in ARPE-19 cells. Alternatively, mCRP can originate from the dissociation of pCRP in the surface of lipopolysaccharide-damaged RPE in both ARPE-19 and primary porcine RPE lines. In addition, we found that the proinflammatory phenotype of mCRP in the RPE depends on its topological localization. Together, our findings further support mCRP contribution to AMD progression enhancing oBRB disruption.

Special collection on eye disease - https://www.aging-us.com/special-collections-archive/eye-disease

Press release - https://www.aging-us.com/news_room/activation-of-c-reactive-protein-proinflammatory-phenotype-in-the-blood-retinal-barrier-in-vitro-implications-for-age-related-macular-degeneration

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DOI - https://doi.org/10.18632/aging.103655

Full text - https://www.aging-us.com/article/103655/text

Correspondence to: Blanca Molins email: bmolins@clinic.cat

Keywords: age-related macular degeneration, retinal pigment epithelium, inflammation, C-reactive protein

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 http://www.Aging-US.com​​ or connect with us on:

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/

Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls

Media Contact
18009220957
MEDIA@IMPACTJOURNALS.COM

Paper Spotlight: Age-related Macular Degeneration and C-reactive Protein

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