Microbiology

Aging (Aging-US)

Aging-US published this research paper as the cover of Volume 14, Issue 22, entitled, "Glutaminase inhibitors rejuvenate human skin via clearance of senescent cells: a study using a mouse/human chimeric model" by researchers from the Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo, Japan.

DOI - https://doi.org/10.18632/aging.204391

Corresponding author - Kento Takaya - kento-takaya312@keio.jp

Abstract

Skin aging caused by various endogenous and exogenous factors results in structural and functional changes to skin components. However, the role of senescent cells in skin aging has not been clarified. To elucidate the function of senescent cells in skin aging, we evaluated the effects of the glutaminase inhibitor BPTES (bis-2-(5-phenylacetamido-1, 3, 4-thiadiazol-2-yl)ethyl sulfide) on human senescent dermal fibroblasts and aged human skin. Here, primary human dermal fibroblasts (HDFs) were induced to senescence by long-term passaging, ionizing radiation, and treatment with doxorubicin, an anticancer drug. Cell viability of HDFs was assessed after BPTES treatment. A mouse/human chimeric model was created by subcutaneously transplanting whole skin grafts from aged humans into nude mice. The model was treated intraperitoneally with BPTES or vehicle for 30 days. Skin samples were collected and subjected to reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, and histological analysis. BPTES selectively eliminated senescent dermal fibroblasts regardless of the method used to induce senescence; aged human skin grafts treated with BPTES exhibited increased collagen density, increased cell proliferation in the dermis, and decreased aging-related secretory phenotypes, such as matrix metalloprotease and interleukin. These effects were maintained in the grafts 1 month after termination of the treatment. In conclusion, selective removal of senescent dermal fibroblasts can improve the skin aging phenotype, indicating that BPTES may be an effective novel therapeutic agent for skin aging.

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Keywords - aging, glutaminase inhibitor, human skin, senescent cell, therapeutic agent

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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Glutaminase Inhibitors Rejuvenate Human Skin via Clearance of Senescent Cells

Oncotarget

Oncotarget published this research paper in Volume 13, entitled, “Essential amino acids as diagnostic biomarkers of hepatocellular carcinoma based on metabolic analysis" by researchers from Department of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan; Department of Clinical Nutrition and Food Management, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan; Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan; Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-0882, Japan; Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.

DOI - https://doi.org/10.18632/oncotarget.28306

Correspondence to - Yuji Morine - ymorine@tokushima-u.ac.jp 

Abstract

Metabolomics, defined as the comprehensive identification of all small metabolites in a biological sample, has the power to shed light on phenotypic changes associated with various diseases, including cancer. To discover potential metabolomic biomarkers of hepatocellular carcinoma (HCC), we investigated the metabolomes of tumor and non-tumor tissue in 20 patients with primary HCC using capillary electrophoresis–time-of-flight mass spectrometry. We also analyzed blood samples taken immediately before and 14 days after hepatectomy to identify associated changes in the serum metabolome. Marked changes were detected in the different quantity of 61 metabolites that could discriminate between HCC tumor and paired non-tumor tissue and additionally between HCC primary tumors and colorectal liver metastases. Among the 30 metabolites significantly upregulated in HCC tumors compared with non-tumor tissues, 10 were amino acids, and 7 were essential amino acids (leucine, valine, tryptophan, isoleucine, methionine, lysine, and phenylalanine). Similarly, the serum metabolomes of HCC patients before hepatectomy revealed a significant increase in 16 metabolites, including leucine, valine, and tryptophan. Our results reveal striking differences in the metabolomes of HCC tumor tissue compared with non-tumor tissue, and identify the essential amino acids leucine, valine, and tryptophan as potential metabolic biomarkers for HCC.

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Keywords - metabolomics, essential amino acid, hepatocellular carcinoma, diagnostic biomarker

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Essential Amino Acids as Diagnostic Biomarkers of Hepatocellular Carcinoma

Mutant library

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QVirus Platform

Oncotarget published this trending research perspective in Volume 13, entitled, "Treasures from trash in cancer research" by researchers from Núcleo de Pesquisas em Oncologia/Universidade Federal do Pará, Belém, Pará, Brazil; Instituto Metrópole Digital/Universidade Federal do Rio Grande do Norte, Natal, Brazil; Instituto de Ciências Biológicas/Universidade Federal do Pará, Belém, Pará, Brazil.

DOI - https://doi.org/10.18632/oncotarget.28308

Correspondence to - Paulo Pimentel de Assumpção - assumpcaopp@gmail.com

Abstract

Introduction: Cancer research has significantly improved in recent years, primarily due to next-generation sequencing (NGS) technology. Consequently, an enormous amount of genomic and transcriptomic data has been generated. In most cases, the data needed for research goals are used, and unwanted reads are discarded. However, these eliminated data contain relevant information. Aiming to test this hypothesis, genomic and transcriptomic data were acquired from public datasets.

Materials and Methods: Metagenomic tools were used to explore genomic cancer data; additional annotations were used to explore differentially expressed ncRNAs from miRNA experiments, and variants in adjacent to tumor samples from RNA-seq experiments were also investigated.

Results: In all analyses, new data were obtained: from DNA-seq data, microbiome taxonomies were characterized with a similar performance of dedicated metagenomic research; from miRNA-seq data, additional differentially expressed sncRNAs were found; and in tumor and adjacent to tumor tissue data, somatic variants were found.

Conclusions: These findings indicate that unexplored data from NGS experiments could help elucidate carcinogenesis and discover putative biomarkers with clinical applications. Further investigations should be considered for experimental design, providing opportunities to optimize data, saving time and resources while granting access to multiple genomic perspectives from the same sample and experimental run.

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Keywords - cancer metagenomics, cancer sncRNA expression, RNA-Seq variant calling

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Treasures From Trash in Cancer Research

Aging-US published this research paper as the cover of Volume 14, Issue 21, entitled, "IGF1 gene therapy in middle-aged female rats delays reproductive senescence through its effects on hypothalamic GnRH and kisspeptin neurons" by researchers from the Laboratorio de Bioquímica del Envejecimiento, Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), Facultad de Ciencias Médicas, UNLP-CONICET, La Plata, Argentina; Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina; Instituto de Farmacología Experimental de Córdoba-CONICET, Departamento de Farmacología, Facultad de Ciencias Químicas, UNC-CONICET, Córdoba, Argentina; Department of Anatomy, Histology and Neuroscience, Autonomous University of Madrid, Madrid, España; Instituto Cajal, CSIC, Madrid, España; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, España.

DOI - https://doi.org/10.18632/aging.204360

Corresponding authors - Maria-Angeles Arevalo - arevalo@cajal.csic.es, and María José Bellini - mariajosebellini@med.unlp.edu.ar

Abstract

The process of aging is the result of progressive loss of homeostasis and functional body impairment, including the central nervous system, where the hypothalamus plays a key role in regulating aging mechanisms. The consequences of aging include a chronic proinflammatory environment in the hypothalamus that leads to decreased secretion of gonadotropin-releasing hormone (GnRH) and impairs kisspeptin neuron functionality.

In this work, we investigated the effect of insulin-like growth factor 1 (IGF1) gene therapy on hypothalamic kisspeptin/GnRH neurons and on microglial cells, that mediate the inflammatory process related with the aging process. The results show that IGF1 rats have higher kisspeptin expression in the anteroventral periventricular (AVPV) nucleus and higher immunoreactivity of GnRH in the arcuate nucleus and median eminence. In addition, IGF1-treated animals exhibit increased numbers of Iba1+ microglial cells and MHCII+/Iba1+ in the AVPV and arcuate nuclei. In conclusion, IGF1 gene therapy maintains kisspeptin production in the AVPV nucleus, induces GnRH release in the median eminence, and alters the number and reactivity of microglial cells in middle-aged female rats. We suggest that IGF1 gene therapy may have a protective effect against reproductive decline.

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Keywords - aging, IGF1, gene therapy, reproductive senescence, GnRH, kisspeptin, microglia

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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IGF1 Gene Therapy in Middle-Aged Female Rats Delays Reproductive Senescence

Aging (Aging-US) published this trending research paper in Volume 14, Issue 20, entitled, “Age-associated changes in microglia activation and Sirtuin-1- chromatin binding patterns” by researchers from San Diego Biomedical Research Institute, San Diego, CA; University of Nebraska Medical Center, Omaha, NE; Oncovalent Therapeutics, Los Angeles, CA.

DOI - https://doi.org/10.18632/aging.204329

Corresponding author - Maria Cecilia Garibaldi Marcondes - cmarcondes@SDBRI.org 

ABSTRACT

The aging process is associated with changes in mechanisms maintaining physiology, influenced by genetics and lifestyle, and impacting late life quality and longevity. Brain health is critical in healthy aging. Sirtuin 1 (Sirt1), a histone deacetylase with silencing properties, is one of the molecular determinants experimentally linked to health and longevity. We compared brain pathogenesis and Sirt1-chromatin binding dynamics in brain pre-frontal cortex from 2 groups of elder rhesus macaques, divided by age of necropsy: shorter-lived animals (18-20 years old (yo)), equivalent to 60-70 human yo; and longer-lived animals (23-29 yo), corresponding to 80-100 human yo and modeling successful aging. These were compared with young adult brains (4-7 yo). Our findings indicated drastic differences in the microglia marker Iba1, along with factors influencing Sirt1 levels and activity, such as CD38 (an enzyme limiting NAD that controls Sirt1 activity) and mir142 (a microRNA targeting Sirt1 transcription) between the elder groups. Iba1 was lower in shorter-lived animals than in the other groups, while CD38 was higher in both aging groups compared to young. mir142 and Sirt1 levels were inversely correlated in longer-lived brains (>23yo), but not in shorter-lived brains (18-20 yo). We also found that Sirt1 binding showed signs of better efficiency in longer-lived animals compared to shorter-lived ones, in genes associated with nuclear activity and senescence. Overall, differences in neuroinflammation and Sirt1 interactions with chromatin distinguished shorter- and longer-lived animals, suggesting the importance of preserving microglia and Sirt1 functional efficiency for longevity.

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Press release - https://www.aging-us.com/news_room/age-associated-changes-in-microglia-activation-and-sirtuin-1-chromatin-binding-patterns

Keywords - aging, brain, rhesus macaques, microglia, Sirtuin-1

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​​ 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/

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

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Age-Associated Changes in Microglia Activation and Sirtuin-1- Chromatin Binding Patterns

Oncotarget published this research paper in Volume 13, entitled, "Tumor hyaluronan as a novel biomarker in non-small cell lung cancer: A retrospective study" by researchers from Gastrointestinal and Neuroendocrine Malignancies, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA; Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA; Department of Radiation Oncology, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY; Lung Cancer Research Program, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA.

DOI - https://doi.org/10.18632/oncotarget.28304

Correspondence to - Andrew E. Hendifar - andrew.hendifar@cshs.org 

Abstract

Introduction: Hyaluronan (HA) accumulation is associated with tumorigenesis and aggressive tumor behavior.

Aims: We investigated the biomarker potential of HA in non-small cell lung cancer (NSCLC).

Methods: HA levels were scored using affinity histochemistry in 137 NSCLC samples stratified by HA score ≤10, 11–20, 21–30, and >30 with HA-high defined as ≥25% expression in the extracellular matrix (ECM) of the tumor surface area. Overall survival (OS) and time to progression from initiation of taxane therapy (TTP) were compared using log-rank tests based on HA score.

Results: Of 122 patients with recurrent/metastatic NSCLC, 93 had mean HA scores that were not significantly different across clinicopathologic variables. Frequency of HA-high tumors did not differ by histology (34/68 adenocarcinomas vs. 12/25 squamous tumors, Fisher’s p = 1.0000). Median OS for recurrent/metastatic adenocarcinoma was 35.5 months (95%, 23.6–50.3) vs. 17.9 months for squamous (95%, 12.7–37.0, log-rank test, p = 0.0165). OS was not significantly different by HA quartiles, high or low (<25) HA score and tumor histology, and HA biopsy site (all p > 0.05). Median TTP (n = 98) significantly differed by HA quartile (2.8 months for HA score ≤10; 5.0 months for 11–20; 7.9 months for 21–30; 3.9 months for >30, p = 0.0265). Improved TTP trended in HA-high over HA-low tumors (n = 98, p = 0.0911).

Conclusion: In this NSCLC cohort, tumor HA level represents a potential biomarker for TTP, which remains a cornerstone of NSCLC therapy. Further validation is warranted to identify the HA accumulation threshold associated with clinical benefit.

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Press release - https://www.oncotarget.com/index.php?journal=oncotarget&page=news&op=press&item=oncotarget-tumor-hyaluronan-as-novel-biomarker-in-non-small-cell-lung-cancer-a-retrospective-study

Keywords - hyaluronan, hyaluronic acid, biomarker, prognostic, predictive

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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