Review
Peripheral Vascular Disease
Hisaya Kato, Yoshiro Maezawa
Summary: HGPS and WS are representative genetic progeroid syndromes that have been extensively studied in the field of aging research. HGPS primarily affects children, while WS exhibits accelerated aging phenotypes after puberty. Studying these diseases can provide insight into the aging-associated development of CVD and explore potential treatment options.
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
(2022)
Article
Cardiac & Cardiovascular Systems
Anahita Mojiri, Brandon K. Walther, Chongming Jiang, Gianfranco Matrone, Rhonda Holgate, Qiu Xu, Elisa Morales, Guangyu Wang, Jianhua Gu, Rongfu Wang, John P. Cooke
Summary: The study on a unique HGPS cell model demonstrated the impact of telomere repair on vascular cell aging, suggesting telomerase mRNA as a potential effective therapeutic approach for HGPS. Research on endothelial cells differentiated from patients with HGPS showed that hTERT treatment improved cellular function, restored endothelial function, and reduced the release of inflammatory markers.
EUROPEAN HEART JOURNAL
(2021)
Article
Genetics & Heredity
Purvi Majethia, Katta Mohan Girisha
Summary: Wiedemann-Rautenstrauch syndrome is a rare genetic disorder characterized by growth retardation, lipoatrophy, a distinctive face, sparse scalp hair, and dental anomalies. It is rarely reported and has been found in an Indian patient as well.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Review
Genetics & Heredity
Noelle J. Batista, Sanket G. Desai, Alexis M. Perez, Alexa Finkelstein, Rachel Radigan, Manrose Singh, Aaron Landman, Brian Drittel, Daniella Abramov, Mina Ahsan, Samantha Cornwell, Dong Zhang
Summary: Hutchinson-Gilford progeria syndrome (HGPS) is a rare, autosomal-dominant, and fatal premature aging syndrome caused by a point mutation in the LMNA gene. The resulting mutant protein, progerin, behaves in a dominant-negative fashion, leading to cellular and molecular changes similar to normal aging cells. However, HGPS manifests in an accelerated manner and primarily affects connective tissues. Epigenetic changes in HGPS have been studied and may play a crucial role in the disease's pathogenesis. Recent treatments for HGPS have shown important effects at a cellular level, improving symptoms and increasing lifespan.
Article
Biochemistry & Molecular Biology
Madaiah Puttaraju, Michaela Jackson, Stephanie Klein, Asaf Shilo, C. Frank Bennett, Leslie Gordon, Frank Rigo, Tom Misteli
Summary: Research has identified an optimized antisense oligonucleotide that can significantly extend lifespan in a mouse model of HGPS, primarily through non-RNase H-mediated mechanisms. In vivo use of optimized ASOs can markedly reduce progerin mRNA levels, but the extent of protein reduction varies between tissues.
Article
Biochemistry & Molecular Biology
Michael R. Erdos, Wayne A. Cabral, Urraca L. Tavarez, Kan Cao, Jelena Gvozdenovic-Jeremic, Narisu Narisu, Patricia M. Zerfas, Stacy Crumley, Yoseph Boku, Gunnar Hanson, Dan V. Mourich, Ryszard Kole, Michael A. Eckhaus, Leslie B. Gordon, Francis S. Collins
Summary: Using an antisense peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) to block pathogenic splicing of mutant transcripts has shown promising results in reducing progerin levels and extending lifespan in a mouse model of Hutchinson-Gilford progeria syndrome.
Article
Cardiac & Cardiovascular Systems
Amanda Sanchez-Lopez, Carla Espinos-Estevez, Cristina Gonzalez-Gomez, Pilar Gonzalo, Maria J. Andres-Manzano, Victor Fanjul, Raquel Riquelme-Borja, Magda R. Hamczyk, Alvaro Macias, Lara Del Campo, Emilio Camafeita, Jesus Vazquez, Anna Barkaway, Loic Rolas, Sussan Nourshargh, Beatriz Dorado, Ignacio Benedicto, Vicente Andres
Summary: The study showed that while targeting progerin in mice with mild symptoms produced more significant benefits, it is never too late to treat Hutchinson-Gilford progeria syndrome (HGPS). Restricting the suppression of progerin and restoration of lamin A to vascular smooth muscle cells and cardiomyocytes can effectively prevent vascular disease and normalize lifespan.
Review
Biochemistry & Molecular Biology
Jon Macicior, Beatriz Marcos-Ramiro, Silvia Ortega-Gutierrez
Summary: Progeria is a rare genetic disorder caused by a point mutation in the lamin A gene, resulting in abnormal accumulation of progerin. Patients typically die prematurely at the average age of 14.5 due to significant alterations in the cardiovascular system, bones, skin, and overall growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Junyeop Kim, Yerim Hwang, Sumin Kim, Yujung Chang, Yunkyung Kim, Youngeun Kwon, Jongpil Kim
Summary: Partial cellular reprogramming using Oct4, Sox2, Klf4, and c-Myc can rejuvenate cells and reduce aged-cell phenotypes. In this study, we demonstrated that activating the endogenous Oct4 gene through CRISPR/dCas9 system can ameliorate aging in a mouse model of Hutchinson-Gilford progeria syndrome. The activated Oct4 expression not only induced epigenetic remodeling and suppressed progerin accumulation, but also rescued vascular pathological features and lifespan shortening. These findings suggest that CRISPR/dCas9-mediated Oct4 activation could be a promising strategy for treating geriatric diseases.
Article
Biochemistry & Molecular Biology
Jui-Chung Chiang, Wei-Min Chen, Ciara Newman, Benjamin P. C. Chen, Hsinyu Lee
Summary: The study reveals the crucial role of LPA(3) in regulating mitochondrial homeostasis, suppressing mitochondrial stress, and improving mitochondrial function. LPA(3) is found to be a promising therapeutic target for maintaining cellular youth and preventing mitochondrial oxidative stress.
Article
Biochemistry & Molecular Biology
Mi Ri Suh, Ikhyun Lim, Jongwook Kim, Pil-Sung Yang, Jin Seung Choung, Hye Ryeong Sim, Sung Chan Ha, MinYoung Kim
Summary: This study reports therapeutic effects of cord blood cells in a patient with HGPS, showing improvements in anthropometric measures, joint ROM, amelioration of atherosclerosis, and dyslipidemia induced by anti-inflammatory and anti-atherosclerotic responses. No serious adverse events were observed throughout the study period and one year beyond.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Yosra Bejaoui, Aleem Razzaq, Noha A. Yousri, Junko Oshima, Andre Megarbane, Abeer Qannan, Ramya Pottabatula, Tanvir Alam, George M. Martin, Henning F. Horn, Thomas Haaf, Steve Horvath, Nady El Hajj
Summary: In this study, the researchers conducted a genome-wide methylation analysis on blood DNA samples from patients with progeroid laminopathies. They found DNA methylation alterations at specific CpG sites and regions, and identified possible pathways/mechanisms involved in the accelerated aging process of progeroid laminopathies. They also observed significant differences in methylation patterns between different subtypes of progeroid laminopathies.
Article
Cell Biology
Wayne A. Cabral, Chris Stephan, Masahiko Terajima, Abhirami A. Thaivalappil, Owen Blanchard, Urraca L. Tavarez, Narisu Narisu, Tingfen Yan, Stephen M. Wincovitch, Yuki Taga, Mitsuo Yamauchi, Kenneth M. Kozloff, Michael R. Erdos, Francis S. Collins
Summary: Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a mutation in the LMNA gene, resulting in the production of the toxic progerin protein. This study used a mouse model of HGPS to investigate the mechanisms of bone loss associated with the disease. The findings revealed abnormal bone formation, reduced bone mass, and increased fragility in the HGPS mice. The study also identified abnormal differentiation of osteoblasts and upregulation of adipogenic genes as contributing factors to the bone abnormalities in HGPS.
Article
Cell Biology
Haihuan Lin, Juliane Mensch, Maria Haschke, Kathrin Jager, Brigitte Kottgen, Jens Dernedde, Evelyn Orso, Michael Walter
Summary: Establishing five immortalized HGP fibroblast cell lines using retroviral infection with the catalytic subunit of hTERT demonstrated enhanced proliferative lifespan and reduced senescence signs, with growth increase and phenotype improvement independent of telomere elongation. The initial telomeric stabilization after hTERT infection and relatively low amounts of hTERT mRNA were sufficient for phenotype improvement, suggesting implications for therapeutic strategies in HGP and other premature aging syndromes.
Article
Pediatrics
Shao-Wen Wu, Lin Li, Fan Feng, Li Wang, Yuan-Yuan Kong, Xiao-Wei Liu, Chenghong Yin
Summary: In this study, a novel WRS-associated gene, POLR3B, was identified, expanding the mutational and phenotypic spectra of POLR3B. Whole-exome sequencing was found to be useful for detecting rare disease-related genetic variants.
ITALIAN JOURNAL OF PEDIATRICS
(2021)
Article
Immunology
Gabor A. Dunay, Madalena Barroso, Mathias Woidy, Marta K. Danecka, Geraldine Engels, Katharina Hermann, Friederike S. Neumann, Kevin Paul, Jan Beime, Gabriele Escherich, Kristin Fehse, Lev Grinstein, Franziska Haniel, Luka J. Haupt, Laura Hecher, Torben Kehl, Christoph Kemen, Markus J. Kemper, Robin Kobbe, Aloisa Kohl, Thomas Klokow, Dominik Noerz, Jakob Olfe, Friderike Schlenker, Jessica Schmiesing, Johanna Schrum, Freya Sibbertsen, Philippe Stock, Stephan Tiede, Eik Vettorazzi, Dimitra E. Zazara, Antonia Zapf, Marc Luetgehetmann, Jun Oh, Thomas S. Mir, Ania C. Muntau, Soren W. Gersting
Summary: This study investigates the long-term immune response of children to SARS-CoV-2. They found that children have higher antibody levels and lower seroprevalence in families with pediatric index cases in a low-incidence setting. Children show sustained antibody responses to SARS-CoV-2.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Immunology
Norman Mangner, Vassili Panagides, David del Val, Mohamed Abdel-Wahab, Lisa Crusius, Eric Durand, Nikolaj Ihlemann, Marina Urena, Costanza Pellegrini, Francesco Giannini, Tomasz Gasior, Wojtek Wojakowski, Martin Landt, Vincent Auffret, Jan-Malte Sinning, Asim N. Cheema, Luis Nombela-Franco, Chekrallah Chamandi, Francisco Campelo-Parada, Erika Munoz-Garcia, Howard C. Herrmann, Luca Testa, Won-Keun Kim, Helene Eltchaninoff, Lars Sondergaard, Dominique Himbert, Oliver Husser, Azeem Latib, Herve Le Breton, Clement Servoz, Philippe Gervais, Melanie Cote, Holger Thiele, David Holzhey, Axel Linke, Josep Rodes-Cabau
Summary: In transcatheter aortic valve related infective endocarditis (IE), absent echocardiographic signs of IE were associated with the same prognosis as evident echocardiographic signs, highlighting the need for early treatment initiation in high-risk patients presenting with positive blood cultures and symptoms of infection after TAVI.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Cardiac & Cardiovascular Systems
Andrea Scotti, Augustin Coisne, Maurizio Taramasso, Juan F. Granada, Sebastian Ludwig, Josep Rodes-Cabau, Philipp Lurz, Jorg Hausleiter, Neil Fam, Susheel K. Kodali, Joel Rosiene, Ari Feinberg, Alberto Pozzoli, Hannes Alessandrini, Luigi Biasco, Eric Brochet, Paolo Denti, Rodrigo Estevez-Loureiro, Christian Frerker, Edwin C. Ho, Vanessa Monivas, Georg Nickenig, Fabien Praz, Rishi Puri, Horst Sievert, Gilbert H. L. Tang, Martin Andreas, Ralph Stephan Von Bardeleben, Karl-Philipp Rommel, Guillem Muntane-Carol, Mara Gavazzoni, Daniel Braun, Benedikt Koell, Daniel Kalbacher, Kim A. Connelly, Jean-Michel Juliard, Claudia Harr, Giovanni Pedrazzini, Giulio Russo, Francois Philippon, Joachim Schofer, Holger Thiele, Matthias Unterhuber, Dominique Himbert, Marina Urena Alcazar, Mirjam G. Wild, Stephan Windecker, Ulrich Jorde, Francesco Maisano, Martin B. Leon, Rebecca T. Hahn, Azeem Latib
Summary: This study aimed to investigate the impact of sex on treatment outcomes in patients with significant tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI). The results showed no significant differences between women and men in terms of 1-year survival, heart failure hospitalization, functional status, and severity of TR after TTVI. Multivariable Cox-regression analysis with inverse probability of treatment weighting (IPTW) demonstrated that TTVI was associated with improved 1-year survival compared to medical therapy alone in both women and men.
EUROPEAN HEART JOURNAL
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Holger Thiele, Steffen Desch, Anne Freund
EUROPEAN HEART JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Sima Khazaei, Carol C. L. Chen, Augusto Faria Andrade, Nisha Kabir, Pariya Azarafshar, Shahir M. Morcos, Josiane Alves Franca, Mariana Lopes, Peder J. Lund, Geoffroy Danieau, Samantha Worme, Lata Adnani, Nadine Nzirorera, Xiao Chen, Gayathri Yogarajah, Caterina Russo, Michele Zeinieh, Cassandra J. Wong, Laura Bryant, Steven Hebert, Bethany Tong, Tianna S. Sihota, Damien Faury, Evan Puligandla, Wajih Jawhar, Veronica Sandy, Mitra Cowan, Emily M. Nakada, Loydie A. Jerome-Majewska, Benjamin Ellezam, Carolina Cavalieri Gomes, Jonas Denecke, Davor Lessel, Marie T. McDonald, Carolyn E. Pizoli, Kathryn Taylor, Benjamin T. Cocanougher, Elizabeth J. Bhoj, Anne-Claude Gingras, Benjamin A. Garcia, Chao Lu, Eric I. Campos, Claudia L. Kleinman, Livia Garzia, Nada Jabado
Summary: Germline histone H3.3 amino acid substitutions, including H3.3G34R/V, cause severe neurodevelopmental syndromes. In this study, knock-in mice with H3.3G34R/V/W mutations were generated to investigate their impact on brain development. The H3.3G34R mutation led to progressive microcephaly, neurodegeneration, and abnormal accumulation of disease-associated microglia, along with neuronal depletion.
Article
Endocrinology & Metabolism
James Yarmolinsky, Emmanouil Bouras, Andrei Constantinescu, Kimberley Burrows, Caroline J. Bull, Emma E. Vincent, Richard M. Martin, Olympia Dimopoulou, Sarah J. Lewis, Victor Moreno, Marijana Vujkovic, Kyong-Mi Chang, Benjamin F. Voight, Philip S. Tsao, Marc J. Gunter, Jochen Hampe, Andrew J. Pellatt, Paul D. P. Pharoah, Robert E. Schoen, Steven Gallinger, Mark A. Jenkins, Rish K. Pai, Dipender Gill Bullet, Kostas K. Tsilidis
Summary: Epidemiological studies have conflicting findings on the relationship between glucose-lowering medication use and cancer risk. This study used genetic analysis to investigate the effect of pharmacological perturbation on cancer risk and found no consistent evidence to support an association between glucose-lowering drug targets and breast, colorectal, prostate, or overall cancer risk.
Article
Genetics & Heredity
Wenqiang Zhang, Li Zhang, Luo M. Yang, Chenghan Xiao, Xueyao Wu, Peijing Yan, Huijie Cui, Chao Yang, Jingwei Zhu, Xuan Wu, Mingshuang R. Tang, Yutong Wang, Lin Chen, Yunjie A. Liu, Yanqiu M. Zou, Ling E. Zhang, Chunxia Yang, Yuqin Yao, Jiayuan Li, Zhenmi S. Liu, Ben Zhang, Xia Jiang
Summary: Epidemiological studies suggest an association between migraine and chronic kidney disease (CKD), but the genetic basis has not been investigated. We aimed to understand the phenotypic and genetic relationships between migraine, CKD, and kidney function to guide interventions for migraine patients.
Article
Biochemistry & Molecular Biology
Petra Buettner, Julia Boettner, Knut Krohn, Ronny Baber, Uwe Platzbecker, Michael Cross, Steffen Desch, Holger Thiele, Sabine Steiner, Dierk Scheinert, Klaus H. Metzeler, Daniela Branzan
Summary: In this pilot study, it was found that clonal hematopoiesis (CH)-associated mutations can be detected in both peripheral blood cells and tissues associated with atherosclerosis, suggesting a potential impact on disease physiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Sara Lindstrom, Lu Wang, Helian Feng, Arunabha Majumdar, Sijia Huo, James Macdonald, Tabitha Harrison, Constance Turman, Hongjie Chen, Nicholas Mancuso, Theo Bammler, Steve Gallinger, Stephen B. Gruber, Marc J. Gunter, Loic Le Marchand, Victor Moreno, Kenneth Offit, Immaculata De Vivo, Tracy A. O'Mara, Amanda B. Spurdle, Ian Tomlinson, Rebecca Fitzgerald, Puya Gharahkhani, Ines Gockel, Janusz Jankowski, Stuart Macgregor, Johannes Schumacher, Jill Barnholtz-Sloan, Melissa L. Bondy, Richard S. Houlston, Robert B. Jenkins, Beatrice Melin, Margaret Wrensch, Paul Brennan, David C. Christiani, Mattias Johansson, James Mckay, Melinda C. Aldrich, Christopher Amos, Maria Teresa Landi, Adonina Tardon, D. Timothy Bishop, Florence Demenais, Alisa M. Goldstein, Mark M. Iles, Peter A. Kanetsky, Matthew H. Law, Laufey T. Amundadottir, Rachael Stolzenberg-Solomon, Brian M. Wolpin, Alison Klein, Gloria Petersen, Harvey Risch, Stephen J. Chanock, Mark P. Purdue, Ghislaine Scelo, Paul Pharoah, Siddhartha Kar, Rayjean J. Hung, Bogdan Pasaniuc, Peter Kraft
Summary: This study quantified the shared genetic contribution to risk of different cancers and identified novel cancer susceptibility loci using data from 12 cancer genome-wide association studies. The results suggest that some genetic risk variants are shared among cancers, but most of cancer heritability is specific to certain tissues. Cross-disease analysis allows for increased statistical power and the identification of new susceptibility regions. Future studies are likely to discover additional regions associated with the risk of multiple cancer types.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Genetics & Heredity
Abdelkrim Saadi, Claire Navarro, Ozge Ozalp, Charles Marques Lourenco, Racha Fayek, Nathalie Da Silva, Athmane Chaouch, Meryem Benahmed, Christian Kubisch, Arnold Munnich, Nicolas Levy, Patrice Roll, Lamia Ali Pacha, Malika Chaouch, Davor Lessel, Annachiara De Sandre-Giovannoli
Summary: Atypical progeroid syndromes (APS) are premature aging syndromes caused by specific LMNA missense variants. This study reports four unrelated boys who harbor homozygosity for the p.Thr528Met variant and present with strikingly homogeneous APS clinical features. Immunofluorescence analysis reveals dysmorphic nuclei with nuclear blebs and aberrant aggregates of emerin or LAP2α in patient-derived cells.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Medicine, General & Internal
Holger Thiele, Uwe Zeymer, Ibrahim Akin, Michael Behnes, Tienush Rassaf, Amir Abbas Mahabadi, Ralf Lehmann, Ingo Eitel, Tobias Graf, Tim Seidler, Andreas Schuster, Carsten Skurk, Daniel Duerschmied, Peter Clemmensen, Marcus Hennersdorf, Stephan Fichtlscherer, Ingo Voigt, Melchior Seyfarth, Stefan John, Sebastian Ewen, Axel Linke, Eike Tigges, Peter Nordbeck, Leonhard Bruch, Christian Jung, Jutta Franz, Philipp Lauten, Tomaz Goslar, Hans-Josef Feistritzer, Janine Poess, Eva Kirchhof, Taoufik Ouarrak, Steffen Schneider, Steffen Desch, Anne Freund, ECLS-SHOCK Investigators
Summary: In patients with acute myocardial infarction complicated by cardiogenic shock, early extracorporeal life support (ECLS) combined with standard medical treatment did not reduce mortality.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Maximilian von Roeder, Mauritius Maeder, Vincent Wahl, Mitsunobu Kitamura, Johannes Rotta Detto Loria, Oliver Dumpies, Karl-Philipp Rommel, Karl-Patrik Kresoja, Stephan Blazek, Ines Richter, Nicolas Majunke, Steffen Desch, Holger Thiele, Philipp Lurz, Mohamed Abdel-Wahab
Summary: This study investigated the prognostic value and clinical utility of left atrial reservoir strain (LARS) in patients undergoing transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS). The results showed that impaired LARS was independently associated with worse outcomes, and LARS assessment allowed for reliable prediction in patients where conventional echocardiographic assessment was unavailable.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING
(2023)
Article
Cardiac & Cardiovascular Systems
Sebastian Rosch, Karl-Philipp Rommel, Stephan Blazek, Karl-Patrik Kresoja, Anne Schoeber, Maximilian von Roeder, Steffen Desch, Holger Thiele, Philipp Lurz, Karl Fengler
Summary: This study pooled data from two previous studies on endovascular ultrasound-based renal denervation (uRDN) and found that uRDN effectively lowered blood pressure for up to 24 months after treatment, with low rates of adverse events.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Clinical Neurology
Lei S. Zhao, Wenhui Zhao, Jin Cao, Yiheng Tu
Summary: This study used genetic data and Mendelian randomization (MR) to reveal the causal relationship between migraine and microstructural white matter (WM). Specifically, the study found that the mode of anisotropy (MO) of the left inferior fronto-occipital fasciculus and the orientation dispersion index (OD) of the right posterior thalamic radiation exerted significant causal effects on migraine. Migraine also had a significant causal effect on the OD of the left superior cerebellar peduncle.
JOURNAL OF HEADACHE AND PAIN
(2023)
Review
Medicine, General & Internal
Johannes Rotta detto Loria, Steffen Desch, Janine Poess, Katharina Kirsch, Holger Thiele, Marcus Sandri
Summary: This systematic review provides a comprehensive evaluation of the clinical application of percutaneous left atrial appendage occlusion (LAAO) in patients with atrial fibrillation (AF) over the past two decades, including anatomical features, patient selection, procedural planning and execution, complications, medical treatment following the procedure, and contemporary outcome data.
JOURNAL OF CLINICAL MEDICINE
(2023)