Review
Geriatrics & Gerontology
Jan Buehring, Michael Hecker, Brit Fitzner, Uwe Klaus Zettl
Summary: A review of the literature found that shorter telomeres in patients with MS were associated with greater disability, lower brain volume, increased relapse rate, and more rapid conversion from relapsing to progressive MS. Despite limited studies, there is substantial evidence supporting the association of telomere length with MS.
Article
Medicine, General & Internal
Leah Zuroff, Ayman Rezk, Koji Shinoda, Diego A. Espinoza, Yehezqel Elyahu, Bo Zhang, Andrew A. Chen, Russell T. Shinohara, Dina Jacobs, Roy N. Alcalay, Thomas F. Tropea, Alice Chen-Plotkin, Alon Monsonego, Rui Li, Amit Bar-Or
Summary: In the study comparing untreated MS patients with normal controls, it was found that MS patients exhibited early and persistent redistribution of naive and memory CD4 T-cell compartments. While most CD4 and CD8 T-cell aging trajectories were similar between groups, MS patients demonstrated abnormal age-associated increases, particularly in patients over 60.
Article
Clinical Neurology
Mei-Jun Shu, Jiarui Li, Yi-Cheng Zhu
Summary: This study found a causal relationship between longer telomere length and increased risk of multiple sclerosis (MS) susceptibility through two-sample Mendelian randomization analysis.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2022)
Article
Biochemistry & Molecular Biology
Gabriela del Carmen Lopez-Armas, Martha Eloisa Ramos-Marquez, Monica Navarro-Meza, Miguel Angel Macias-Islas, Ana Miriam Saldana-Cruz, Abraham Zepeda-Moreno, Fernando Siller-Lopez, Jose Alfonso Cruz-Ramos
Summary: This study evaluated the peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) in patients with relapsing-remitting multiple sclerosis (RRMS). The results showed a linear correlation between LTL and mtDNA-CN in mild-moderate disability RRMS patients. Moreover, LTL can predict the severity of disability in RRMS patients, and the prediction accuracy can be improved by combining LTL with age.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Public, Environmental & Occupational Health
Fang Xia, Qingwen Li, Xin Luo, Jinyi Wu
Summary: This study analyzed the association between leukocytes telomere length (LTL) and urinary metals. The results showed a negative correlation between urinary cadmium (Cd) and LTL in the US population, and a positive association between urinary molybdenum (Mo) and LTL in the elderly. An artificial neural network (ANN) model was constructed for LTL prediction, which showed a low error rate.
FRONTIERS IN PUBLIC HEALTH
(2022)
Article
Cell Biology
Abraham Aviv
Summary: Approximately 25 trillion erythrocytes circulate in the bloodstream of an adult human, outnumbering leukocytes by a factor of about 1000. The turnover rate of erythrocytes accounts for approximately 76% of the turnover rate of all circulating blood cells. Therefore, erythropoiesis is the main factor causing telomere shortening in hematopoietic cells, which has significant implications for understanding the relationship between telomere length dynamics, health, and lifespan in modern humans.
Article
Biochemistry & Molecular Biology
Michael Hecker, Jan Buehring, Brit Fitzner, Paulus Stefan Rommer, Uwe Klaus Zettl
Summary: Telomeres, protective structures at the ends of chromosomes, are linked to biological aging and disorders like MS. Genetic, environmental, and lifestyle factors influence telomere length and MS susceptibility, with early-life factors like obesity, inactivity, smoking, and vitamin D deficiency associated with reduced TL and higher MS risk. Further research is needed to understand the role of telomeres in disease processes and potential interventions in MS.
Article
Immunology
Qiao Liao, Jian He, Fa-Fa Tian, Fang-Fang Bi, Kun Huang
Summary: The study suggests a potential causal effect of leukocyte telomere length (LTL) on the risk of multiple sclerosis (MS). Genetically predicted shorter LTL could increase the risk of MS in the European population. LTL should be noted and emphasized in the pathogenesis and treatment of MS.
FRONTIERS IN IMMUNOLOGY
(2022)
Letter
Clinical Neurology
Viola Baione, Marco Canevelli, Daniele Belvisi, Maria Chiara Buscarinu, Gianmarco Bellucci, Roberta Fantozzi, Carolina Gabri Nicoletti, Giorgia Malatuni, Antonio Cortese, Laura De Giglio, Matteo Tartaglia, Gina Ferrazzano, Leonardo Malimpensa, Giorgio Leodori, Giuseppe Bruno, Elisabetta Ferraro, Girolama Alessandra Marfia, Diego Centonze, Marco Salvetti, Antonella Conte
Summary: Recent cross-sectional investigations have shown a relationship between Frailty Index (FI) and multiple sclerosis (MS). However, the association between frailty and relapse activity in MS is still unknown. A one-year follow-up study with 471 patients found that there was an inverse association between baseline FI score and the presence of relapse. These findings suggest that frailty may reflect the underlying mechanisms of MS disease activity and FI could be used as an enrichment criterion in clinical trials.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2023)
Review
Immunology
Jasper Iske, Tomohisa Matsunaga, Hao Zhou, Stefan G. Tullius
Summary: The transplantation of aged organs may have negative effects on recipients due to the accumulation of senescent cells, which can promote aging in recipient cells through the secretion of pro-inflammatory molecules. Studies have shown that transplanting old organs may limit the physical reserve of recipients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Dries S. Martens, Charlotte Van der Stukken, Catherine Derom, Evert Thiery, Esm Ee M. Bijnens, Tim S. Nawrot
Summary: The study found that there is a correlation between telomere length at birth and later in life in both children and adults. The ranking of telomere length tends to be stable over time, indicating the importance of understanding the initial setting of newborn telomere length and its significance for later life. Additionally, longer maternal telomere length is associated with lower telomere attrition in the next generation.
Review
Immunology
Maria Dema, Herena Eixarch, Luisa M. Villar, Xavier Montalban, Carmen Espejo
Summary: The number of elderly multiple sclerosis patients is increasing due to improved life expectancy and available treatments. Current treatments cannot halt disability accumulation associated with disease progression, potentially due to the impact of immunosenescence, leading to abnormal immune cell subsets contributing to autoimmune disease development. Strategies including senolytics, regenerative therapies, and rejuvenation of immune cells have been proposed to potentially reverse immunosenescence and benefit MS progression.
AUTOIMMUNITY REVIEWS
(2021)
Article
Cell Biology
Aenne S. von Falkenhausen, Rebecca Freudling, Melanie Waldenberger, Christian Gieger, Annette Peters, Martina Mueller-Nurasyid, Stefan Kaeaeb, Moritz F. Sinner
Summary: This study aimed to investigate the association between ECG measures and telomere length, as well as their relationship with cardiac pathologies. The results showed that while ECG measures were influenced by age, they were not associated with shortened telomere length as a marker of biological aging.
Article
Clinical Neurology
Gina P. Sykes, Joseph Kamtchum-Tatuene, Sarina Falcione, Sarah Zehnder, Danielle Munsterman, Boryana Stamova, Bradley P. Ander, Frank R. Sharp, Glen Jickling
Summary: This study identified 166 genes associated with age in patients with acute ischemic stroke, with 69 of these genes confirmed in a validation cohort. The identified genes were related to changes in B-cell receptor signaling, lymphocyte proliferation, and leukocyte homeostasis, suggesting that aging immune system may influence age-related stroke risk and outcome.
Article
Biochemistry & Molecular Biology
Inmaculada Rodriguez-Martin, Gonzalo Villanueva-Martin, Alfredo Guillen-Del-Castillo, Norberto Ortego-Centeno, Jose L. Callejas, Carmen P. Simeon-Aznar, Javier Martin, Marialbert Acosta-Herrera
Summary: By using the two-sample Mendelian randomization approach, this study reveals a causal relationship between telomere length in leukocytes and systemic sclerosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Andreas Hoeflich, Brit Fitzner, Christina Walz, Michael Hecker, Armin Tuchscherer, Julia Brenmoehl, Uwe Klaus Zettl
Summary: The study investigated the IGF system in MS patients during TCA treatment, finding that IGF-I levels increased in serum while fragmentation of IGFBP-2 and IGFBP-3 decreased in CSF. The reduction in IGFBP fragmentation and lower ratio of IGF-II to intact IGFBPs indicate a regulation of IGF-II bioactivity in CSF during repeated intrathecal TCA administration in MS patients.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Elena Putscher, Michael Hecker, Brit Fitzner, Peter Lorenz, Uwe Klaus Zettl
Summary: Splicing is a crucial RNA processing step, with genetic variations playing a role in altering this process and contributing to the development of diseases. The splicing pattern can be examined through gene expression analyses, computational tools, and splicing reporter minigene assays. These assays, like pDESTsplice and pSpliceExpress, offer a way to study alternative splicing events and understand disease mechanisms better.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Niklas Frahm, Michael Hecker, Uwe Klaus Zettl
Summary: Polypharmacy is common among elderly and chronically ill patients, especially those with dementia, PD, or MS. The main predictor of polypharmacy is the complex symptom profile of these neurological disorders. Negative impacts associated with polypharmacy include potentially inappropriate medication, drug-drug interactions, and poor quality of life.
CURRENT PHARMACEUTICAL DESIGN
(2021)
Article
Medicine, General & Internal
Michael Hecker, Brit Fitzner, Elena Putscher, Margit Schwartz, Alexander Winkelmann, Stefanie Meister, Ales Dudesek, Dirk Koczan, Peter Lorenz, Nina Boxberger, Uwe Klaus Zettl
Summary: This study found that MS-associated SNPs can affect the expression of mature miRNAs and provided insights into the dysregulation of miRNAs in MS. Further studies on the maturation and function of miRNAs in different cell types and tissues may help to gain a more detailed functional understanding of the genetic basis of MS.
Article
Pharmacology & Pharmacy
Paula Bachmann, Niklas Frahm, Jane Louisa Debus, Pegah Mashhadiakbar, Silvan Elias Langhorst, Barbara Streckenbach, Julia Baldt, Felicita Heidler, Michael Hecker, Uwe Klaus Zettl
Summary: Polypharmacy is a common problem in modern medicine, especially among patients with chronic diseases such as multiple sclerosis. This study aimed to assess the prevalence and clinical relevance of polypharmacy and potential drug-drug interactions (pDDIs) in multiple sclerosis patients. The findings revealed that the majority of patients had polypharmacy and at least one pDDI.
Article
Health Care Sciences & Services
Silvan Elias Langhorst, Niklas Frahm, Michael Hecker, Pegah Mashhadiakbar, Barbara Streckenbach, Julia Baldt, Felicita Heidler, Uwe Klaus Zettl
Summary: This study investigated the vaccination status, vaccination card knowledge, and vaccination behavior of multiple sclerosis (MS) patients. The results showed that the vaccination coverage for tetanus, diphtheria, pertussis, and poliomyelitis was relatively high, but there were some patients with incomplete vaccination or incorrect self-reported vaccination status. Patients who did not have regular vaccination card checks were more likely to be male and had lower knowledge and willingness regarding vaccination.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Michael Hecker, Niklas Frahm, Paula Bachmann, Jane Louisa Debus, Marie-Celine Haker, Pegah Mashhadiakbar, Silvan Elias Langhorst, Julia Baldt, Barbara Streckenbach, Felicita Heidler, Uwe Klaus Zettl
Summary: This study compared three different screening tools for the detection and classification of potential drug-drug interactions (pDDIs) in multiple sclerosis (MS) patients, and identified factors associated with severe pDDIs. The results showed heterogeneity in the information on pDDIs between the examined databases, suggesting that multiple resources should be used in clinical practice to evaluate pDDIs. Regular medication reviews and information exchange between treating physicians can help prevent severe pDDIs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Elena Putscher, Michael Hecker, Brit Fitzner, Nina Boxberger, Margit Schwartz, Dirk Koczan, Peter Lorenz, Uwe Klaus Zettl
Summary: This study found that genetic variants from MS risk loci affect pre-mRNA splicing. These findings substantiate the role of alternative splicing events in the genetics of MS. Further research on how disease-causing genetic variants modify the interactions between splicing regulatory sequence elements and RNA-binding proteins can help deepen our understanding of the genetic susceptibility to MS.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Franziska Alfen, Elena Putscher, Michael Hecker, Uwe Klaus Zettl, Andreas Hermann, Jan Lukas
Summary: Fabry disease is a rare genetic disorder caused by mutations in the GLA gene. This study investigated the impact of these mutations on splicing behavior and found that abnormal splicing can lead to reduced enzyme activity and affect treatment options. Experimental analysis confirmed alternative splicing events for specific mutations, highlighting the importance of splicing phenotype analysis in studying exonic GLA gene mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Marie-Celine Haker, Niklas Frahm, Michael Hecker, Silvan Elias Langhorst, Pegah Mashhadiakbar, Jane Louisa Debus, Barbara Streckenbach, Julia Baldt, Felicita Heidler, Uwe Klaus Zettl
Summary: This study investigated the use of drugs with potential harm to the development of an unborn child in women with multiple sclerosis (MS). The majority of patients were found to be using drugs that are rated as having a potential risk of interfering with normal foetal development. More effective contraception and special pregnancy information programmes should be implemented to reduce potential risks to mother and child.
THERAPEUTIC ADVANCES IN DRUG SAFETY
(2023)
Article
Hematology
Robby Engelmann, Nadja Jaekel, Sabrina Jotschke, Beatrice Ludwig-Kraus, Frank Bernhard Kraus, Neha Kumari, Susann Schulze, Michael Hecker, Christina Zahn, Haifa Kathrin Al-Ali, Christian Junghanss, Sebastian Boettcher
Summary: In this study, the mechanisms of severe acute respiratory syndrome coronavirus 2 vaccination success in patients with hematological neoplasia were elucidated. The study found that patients with lymphoid malignancies had insufficient IgG response but healthy CD4+ T-cell function, while patients with myeloid neoplasia had fewer spike-specific CD4+ responses but normal seroconversion rate. It was also observed that vector-based vaccines were more effective in inducing CD4+ and CD8+ T-cell responses. The study provides valuable insights for tailored vaccination strategies in patients with hematological neoplasia.
Article
Immunology
Michael Hecker, Brit Fitzner, Nina Boxberger, Elena Putscher, Robby Engelmann, Wendy Bergmann, Michael Mueller, Isis Ludwig-Portugall, Margit Schwartz, Stefanie Meister, Ales Dudesek, Alexander Winkelmann, Dirk Koczan, Uwe Klaus Zettl
Summary: This study aimed to analyze the gene expression pattern of B cells before and during immune reconstitution therapy (IRT) in order to better understand the therapeutic effects and identify potential biomarkers of clinical response. The study found that B cells exhibited a distinct gene expression signature during IRT, and identified genes that could potentially indicate relapse risk.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Medicine, General & Internal
Julia Baldt, Niklas Frahm, Michael Hecker, Barbara Streckenbach, Silvan Elias Langhorst, Pegah Mashhadiakbar, Katja Burian, Janina Meissner, Felicita Heidler, Jorg Richter, Uwe Klaus Zettl
Summary: Polypharmacy is a significant issue in patients with multiple sclerosis, and it is associated with depression severity and comorbidities. A study on 374 MS patients found that patients with higher depression severity were more likely to be taking multiple medications, while anxiety was not correlated with polypharmacy. Furthermore, the frequency of comorbidities showed a positive correlation with anxiety and depression scores.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Jane Louisa Debus, Paula Bachmann, Niklas Frahm, Pegah Mashhadiakbar, Silvan Elias Langhorst, Barbara Streckenbach, Julia Baldt, Felicita Heidler, Michael Hecker, Uwe Klaus Zettl
Summary: This study aimed to determine the frequency and severity of potential drug-drug interactions (pDDIs) and potential drug-food interactions (pDFIs) in patients with multiple sclerosis (PwMS) who are taking multiple medications. The study found that patients with polypharmacy were particularly at risk of severe pDDIs.
THERAPEUTIC ADVANCES IN CHRONIC DISEASE
(2022)
