Review
Cell Biology
Ruchi Kumari, Parmjit Jat
Summary: Cellular senescence is a stable cell cycle arrest triggered in response to various stimuli, characterized by dynamic changes in senescent cells. It has both positive effects on tissue repair and anti-cancer mechanisms, but can also negatively impact organismal health. Multiple pathways, including p53/p21 and p16/pRB, play central roles in regulating this process.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Thomas Aschacher, Daniela Geisler, Verena Lenz, Olivia Aschacher, Bernhard Winkler, Anne-Kristin Schaefer, Andreas Mitterbauer, Brigitte Wolf, Florian K. Enzmann, Barbara Messner, Guenther Laufer, Marek P. Ehrlich, Martin Grabenwoeger, Michael Bergmann
Summary: This study aimed to investigate the impacts of chronic hypoxia and telomeric DNA damage on cellular homeostasis and vascular degeneration of thoracic aortic aneurysm (TAA). The results revealed the association of chronic hypoxia with telomeric DNA damage, induction of senescence-associated secretory phenotype (SASP), increase in CD163(+) macrophages, and correlation between hypoxic DNA damage and the number of aortic telocytes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Tadahito Yasuda, Mayu Koiwa, Atsuko Yonemura, Keisuke Miyake, Ryusho Kariya, Sho Kubota, Takako Yokomizo-Nakano, Noriko Yasuda-Yoshihara, Tomoyuki Uchihara, Rumi Itoyama, Luke Bu, Lingfeng Fu, Kota Arima, Daisuke Izumi, Shiro Iwagami, Kojiro Eto, Masaaki Iwatsuki, Yoshifumi Baba, Naoya Yoshida, Hiroto Ohguchi, Seiji Okada, Keisuke Matsusaki, Goro Sashida, Akiko Takahashi, Patrick Tan, Hideo Baba, Takatsugu Ishimoto
Summary: In the tumor microenvironment, senescent cancer-associated fibroblasts (CAFs) play a role in promoting gastric cancer (GC) peritoneal tumor formation through maintenance of the senescence-associated secretory phenotype (SASP) and JAK/STAT3 signaling. Single-cell mass cytometry analysis revealed a high expression level of senescent fibroblasts and SASP factors in the ascites of GC patients. These findings provide insights into the molecular mechanisms of inflammation-related SASP maintenance and the involvement of senescent CAFs in GC peritoneal dissemination.
Review
Cell Biology
Runjiu Zhu, Haoyang Wan, Hong Yang, Mingrui Song, Yu Chai, Bin Yu
Summary: With the increasing proportion of older individuals in most countries, the prevalence of osteoporosis has been on the rise, leading scientists to focus on the pathogenic mechanisms of this condition. In recent years, research on cellular senescence has shed light on the role of the senescent microenvironment in osteoporosis. Senescent cells in the bone marrow secrete senescence-associated secretory phenotype (SASP) factors, which can impact both their own function and the surrounding healthy cells, exacerbating the aging process. The composition of SASP may vary depending on the cause of osteoporosis. This review summarizes the relationship between SASP factors and osteoporosis and provides new insights for the investigation of its mechanism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Oncology
Cecilia R. Chambers, Shona Ritchie, Brooke A. Pereira, Paul Timpson
Summary: Senescence is a cellular state where cells halt the cell cycle in response to stress, with senescent cancer cells and adjacent cells potentially remaining metabolically active and secreting pro-inflammatory factors known as the SASP. The SASP plays a critical role in tumorigenesis, affecting various processes and treatment efficacy. Future research on therapy-induced senescence and pharmacological manipulation may provide new avenues for cancer therapeutics.
MOLECULAR ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yoko Tanaka, Akiko Takahashi
Summary: Cellular senescence serves as an important tumor suppression mechanism by inhibiting the proliferation of damaged cells. Irreparable DNA damage in senescent cells leads to the accumulation of genomic DNA fragments in the cytoplasm, triggering the secretion of inflammatory proteins and increasing the release of small extracellular vesicles. This phenomenon, known as senescence-associated secretory phenotype, plays a role in various physiological and pathological processes in the body.
JOURNAL OF BIOCHEMISTRY
(2021)
Article
Cell Biology
Ryan Wallis, Natasa Josipovic, Hannah Mizen, Arturo Robles-Tenorio, Eleanor J. Tyler, Argyris Papantonis, Cleo L. Bishop
Summary: The secretion of small extracellular vesicles (EVs) by senescent cells is found to play an important role in aging and age-related pathologies. Separating the soluble SASP from the vesicular component helps clarify the functional significance of EVs and provides a framework for future investigations.
JOURNAL OF EXTRACELLULAR VESICLES
(2021)
Review
Immunology
Ziqi Yue, Lulingxiao Nie, Pengfei Zhao, Ning Ji, Ga Liao, Qi Wang
Summary: The senescence-associated secretory phenotype (SASP) is a crucial driver of chronic inflammation and aging phenotypes, and it also plays a role in the pathogenesis of multiple oral diseases. This article used bibliometric analysis to examine the composition of SASP and found that cytokines, growth factors, proteases, lipid metabolites, and extracellular vesicles are the main components. Based on the evidence, a hypothetical framework for the progression of SASP-related oral pathology was proposed, and potential therapies targeting specific SASP factors were suggested.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Angelica Giuliani, Anna Maria Giudetti, Daniele Vergara, Laura Del Coco, Deborah Ramini, Sara Caccese, Matilde Sbriscia, Laura Graciotti, Gianluca Fulgenzi, Luca Tiano, Francesco Paolo Fanizzi, Fabiola Olivieri, Maria Rita Rippo, Jacopo Sabbatinelli
Summary: Cellular senescence is closely linked to endothelial dysfunction, resulting in chronic inflammation and vascular impairments. The metabolic behavior of senescent endothelial cells is complex and plays a role in the proinflammatory phenotype.
Article
Dermatology
Marie-Sophie Narzt, Vera Pils, Christopher Kremslehner, Ionela-Mariana Nagelreiter, Markus Schosserer, Emilia Bessonova, Alina Bayer, Raffaela Reifschneider, Lucia Terlecki-Zaniewicz, Petra Waidhofer-Soellner, Michael Mildner, Erwin Tschachler, Maria Cavinato, Sophia Wedel, Pidder Jansen-Duerr, Lucia Nanic, Ivica Rubelj, Abdoelwaheb El-Ghalbzouri, Samuele Zoratto, Martina Marchetti-Deschmann, Johannes Grillari, Florian Gruber, Ingo Laemmermann
Summary: During aging, skin accumulates senescent cells which play a key role in tissue repair and homeostasis when transiently present. However, the persistence of senescent cells that evade clearance leads to age-related deterioration of the skin. Research suggests that lysophospholipids may contribute to immune evasion and chronic inflammation in skin aging.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Pharmacology & Pharmacy
Kazuyuki Okamura, Miyuki Sato, Takehiro Suzuki, Keiko Nohara
Summary: This study found that exposure to arsenite induces premature senescence in hepatic stellate cells and leads to upregulation of SASP factors. The SASP factors released by senescent cells can promote hepatic carcinogenesis.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Correction
Cell Biology
Remi-Martin Laberge, Yu Sun, Arturo V. Orjalo, Christopher K. Patil, Adam Freund, Lili Zhou, Samuel C. Curran, Albert R. Davalos, Kathleen A. Wilson-Edell, Su Liu, Chandani Limbad, Marco Demaria, Patrick Li, Gene B. Hubbard, Yuji Ikeno, Martin Javors, Pierre-Yves Desprez, Christopher C. Benz, Pankaj Kapahi, Peter S. Nelson, Judith Campisi
Summary: Correction to the paper has been published.
NATURE CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
M. E. Cicardi, J. H. Hallgren, D. Mawrie, K. Krishnamurthy, S. S. Markandaiah, A. T. Nelson, V. Kankate, E. N. Anderson, P. Pasinelli, U. B. Pandey, C. M. Eischen, D. Trotti
Summary: The intronic hexanucleotide repeat expansion in the C9orf72 gene is translated into dipeptide repeat proteins, specifically poly proline-arginine (PR), which accumulates in the nucleolus and causes nucleolar stress and increased p53 levels in neurons. Decreasing p53 levels can reduce PR-induced neurotoxicity, and PR does not induce senescence but rather programmed cell death via caspase-3 activation.
Article
Biochemistry & Molecular Biology
Xiaojing Du, Xingxing Zhang, Zhuoran Qi, Ziyi Zeng, Ye Xu, Zhijie Yu, Xin Cao, Jinglin Xia
Summary: This study investigated the relationship between the senescence-associated secretory phenotype (SASP) and stemness in intrahepatic cholangiocarcinoma (ICC). The researchers identified senescence-related stemness genes (SRSGs) in ICC and established a classification based on these genes. They also developed a risk score model for ICC and found positive correlations between the risk score, stemness, immune infiltration, metabolism, and oncogenic signatures in ICC. Additionally, the study demonstrated the up-regulation of HELLS, a SRSG, in tumor-repopulating cells with stemness features and its role in colony size, migration, invasion, and SASP in ICC.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Gastroenterology & Hepatology
Jian-Wei Zhang, Dan Zhang, Hai-Sen Yin, Han Zhang, Kun-Qiao Hong, Jing-Ping Yuan, Bao-Ping Yu
Summary: Chemotherapy induces senescence in cancer cells and senescent cells secrete SASP, which promotes cancer recurrence and chemoresistance. The gut microbiota is closely associated with cancer progression, but the relationship between the gut microbiota and therapy-induced senescent cells is not well understood. This study revealed that F. nucleatum promotes the secretion of chemotherapy-induced SASP in ESCC cells, driving ESCC progression and chemoresistance.
Article
Health Care Sciences & Services
Marietta Hamberger, Nensi Ikonomi, Julian Schwab, Silke Werle, Axel Fuerstberger, Angelika M. R. Kestler, Martin Holderried, Udo X. Kaisers, Florian Steger, Hans A. Kestler
Summary: Empowerment in health care is implemented as a patient-centered approach, with many mHealth apps being developed for individual users. Integrating mHealth apps into the health care system can address challenges such as incomplete medical data and lack of communication. However, concerns about data security, regional differences in regulations, accessibility, and transparency hinder the successful integration. Rethinking the interpretation of empowerment could positively impact intersectoral communication and facilitate secure data sharing.
JMIR MHEALTH AND UHEALTH
(2022)
Editorial Material
Statistics & Probability
Maurizio Vichi, Andrea Ceroli, Hans A. Kestler, Akinori Okada, Claus Weihs
ADVANCES IN DATA ANALYSIS AND CLASSIFICATION
(2022)
Article
Biochemical Research Methods
Christoph Muessel, Nensi Ikonomi, Silke D. Werle, Felix M. Weidner, Markus Maucher, Julian D. Schwab, Hans A. Kestler
Summary: This article introduces a method called CANTATA, which supports the integration of information into regulatory networks and retrieves potential underlying regulations by optimizing the static and dynamic properties of these networks. The results show that the algorithm can predict missing interactions and the resulting models can be used to hypothesize the biological impact.
Article
Cell Biology
Kavitha Shaga Devan, Hans A. Kestler, Clarissa Read, Paul Walther
Summary: Semantic segmentation of electron microscopy images using deep learning methods is a valuable tool for analyzing cell structures. This study introduces a weighted average ensemble model that can automatically segment biological structures in electron microscopy images using a small dataset. The experiments show quantitative and qualitative improvements, and the Grad-CAM method is used for interpretation and verification.
HISTOCHEMISTRY AND CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Fatima Khalid, Tamara Phan, Mingyue Qiang, Pallab Maity, Theresa Lasser, Sebastian Wiese, Marianna Penzo, Marius Alupei, Donata Orioli, Karin Scharffetter-Kochanek, Sebastian Iben
Summary: Mutations in the TFIIH gene are associated with diseases such as xeroderma pigmentosum, trichothiodystrophy, and Cockayne syndrome. The proteome of trichothiodystrophy cells shows reduced stress-sensitivity, while the translational fidelity of their ribosomes is decreased. Treatment with N-acetyl cysteine can restore translational fidelity in trichothiodystrophy cells.
HUMAN MOLECULAR GENETICS
(2023)
Article
Clinical Neurology
Sonja Schoenecker, Verena Hoffmann, Fady Albashiti, Reinhard Thasler, Marlien Hagedorn, Marie-Luise Louiset, Anna Kopczak, Jennifer Roesler, Enayatullah Baki, Silke Wunderlich, Florian Kohlmayer, Klaus Kuhn, Martin Boeker, Johannes Tuennerhoff, Sven Poli, Ulf Ziemann, Oliver Kohlbacher, Katharina Althaus, Susanne Mueller, Albert Ludolph, Hans A. Kestler, Ulrich Mansmann, Marianne Dieterich, Lars Kellert
Summary: This study aims to validate a prediction score for the 3-month functional outcome after juvenile stroke or transient ischemic attack (TIA) in a multi-center observational cohort study. The prediction score has been derived from a retrospective analysis and will be compared to observed clinical outcomes. The importance of this study lies in its potential to personalize counseling and treatment for juvenile stroke patients.
Article
Computer Science, Interdisciplinary Applications
Matthias Ganzinger, Max Blumenstock, Axel Fuerstberger, Leonard Greulich, Hans A. Kestler, Michael Marschollek, Christian Niklas, Tim Schneider, Cord Spreckelsen, Erik Tute, Julian Varghese, Martin Dugas
Summary: Structured documentation of findings is important in clinical research and patient care. Integration of electronic case report forms (eCRF) with electronic health records (EHR) is challenging when researchers from different institutions collaborate. To address this issue, a novel architecture for a federated electronic data capture system (fEDC) was proposed.
JOURNAL OF BIOMEDICAL INFORMATICS
(2023)
Article
Virology
Alan Bareiss, Gunalp Uzun, Marco Mikus, Matthias Becker, Karina Althaus, Nicole Schneiderhan-Marra, Axel Fuerstberger, Julian D. D. Schwab, Hans A. A. Kestler, Martin Holderried, Peter Martus, Katja Schenke-Layland, Tamam Bakchoul
Summary: This study investigates self-reported side effects after COVID-19 vaccination and finds that the frequency of local and systemic side effects differs significantly between mRNA and vector-based vaccines, and is associated with vaccine type, age, and gender.
Article
Medicine, General & Internal
Una Ebong, Susanne Martina Buettner, Stefan A. Schmidt, Franziska Flack, Patrick Korf, Lynn Peters, Beate Gruener, Steffen Stenger, Thomas Stamminger, Hans Kestler, Meinrad Beer, Christopher Kloth
Summary: This study implemented an AI-based software prototype for the detection of COVID-19 pneumonia and differentiation between other types of pneumonia in lung CT datasets. The software achieved a sensitivity of 80.8% and a specificity of 50% for detecting COVID-19, but the human radiologist achieved a higher specificity of 97.2%.
Article
Computer Science, Artificial Intelligence
Felix M. Weidner, Julian D. Schwab, Sabine Woelk, Felix Rupprecht, Nensi Ikonomi, Silke D. Werle, Steve Hoffmann, Michael Kuehl, Hans A. Kestler
Summary: The dynamics of cellular mechanisms can be studied through network analysis. Logic-based models are a popular and simple modeling strategy, but their simulation complexity grows exponentially instead of linearly with the number of nodes. This study applies logic modeling to quantum computing to simulate cellular networks and demonstrates the benefits, such as complexity reduction and quantum algorithms for systems biology tasks. A model of mammalian cortical development is implemented to showcase the applicability of this approach, and results from quantum processing units and a noisy simulator are presented, along with discussions on current technical challenges.
Article
Computer Science, Interdisciplinary Applications
Axel Fuerstberger, Nensi Ikonomi, Angelika M. R. Kestler, Ralf Marienfeld, Julian D. Schwab, Peter Kuhn, Thomas Seufferlein, Hans A. Kestler
Summary: AMBAR is an interactive web application developed to support personalized decision-making in Molecular Tumor Boards (MTBs), improving the analysis and documentation of patients' data for therapeutic interventions.
COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
(2023)
Article
Cell Biology
Gaojie Zhu, Fatima Khalid, Danhui Zhang, Zhouli Cao, Pallab Maity, Hans A. Kestler, Donata Orioli, Karin Scharffetter-Kochanek, Sebastian Iben
Summary: Mutations in various genes can cause the childhood disorder TTD, which is classified as a DNA repair disease or a transcription syndrome. Knockout/knockdown of TTDN1 and RNF113A resulted in consistent effects on ribosomal biogenesis and performance. Interference with these TTD factors led to downregulation of RNA polymerase I transcription, disrupted rRNA processing, reduced rRNA 18S backbone, impaired protein translation decoding, and accumulation of misfolded and carbonylated proteins, suggesting loss of protein homeostasis. This study proposes that ribosomal dysfunction is a common underlying mechanism in TTD.
Article
Biochemical Research Methods
Felix M. Weidner, Mirko Rossini, Joachim Ankerhold, Hans A. Kestler
Summary: This article presents a protocol for implementing Boolean network dynamics as quantum circuits. It provides steps for accessing cloud-based quantum processing units offered by IBM and IonQ, parsing logic for gene regulatory networks, performing simulations of quantum circuits on local devices, and visualizing measurement results. For complete details on the use and execution of this protocol, please refer to Weidner et al.1.