scholarly journals Genetic, Environmental and Lifestyle Determinants of Accelerated Telomere Attrition as Contributors to Risk and Severity of Multiple Sclerosis

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1510
Author(s):  
Michael Hecker ◽  
Jan Bühring ◽  
Brit Fitzner ◽  
Paulus Stefan Rommer ◽  
Uwe Klaus Zettl
Keyword(s):  
Multiple Sclerosis ◽  
Wide Spectrum ◽  
Lifestyle Changes ◽  
Cellular Aging ◽  
Therapeutic Interventions ◽  
Biological Aging ◽  
Telomere Attrition ◽  
The Central Nervous System ◽  
Protective Structures ◽  
Linear Chromosomes

Telomeres are protective structures at the ends of linear chromosomes. Shortened telomere lengths (TL) are an indicator of premature biological aging and have been associated with a wide spectrum of disorders, including multiple sclerosis (MS). MS is a chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system. The exact cause of MS is still unclear. Here, we provide an overview of genetic, environmental and lifestyle factors that have been described to influence TL and to contribute to susceptibility to MS and possibly disease severity. We show that several early-life factors are linked to both reduced TL and higher risk of MS, e.g., adolescent obesity, lack of physical activity, smoking and vitamin D deficiency. This suggests that the mechanisms underlying the disease are connected to cellular aging and senescence promoted by increased inflammation and oxidative stress. Additional prospective research is needed to clearly define the extent to which lifestyle changes can slow down disease progression and prevent accelerated telomere loss in individual patients. It is also important to further elucidate the interactions between shared determinants of TL and MS. In future, cell type-specific studies and advanced TL measurement methods could help to better understand how telomeres may be causally involved in disease processes and to uncover novel opportunities for improved biomarkers and therapeutic interventions in MS.

scholarly journals Fibromyalgia: Presentation and Management with a Focus on Pharmacological Treatment

2008 ◽  
Vol 13 (6) ◽  
pp. 477-483 ◽  
Author(s):  
Janice E Sumpton ◽  
Dwight E Moulin
Keyword(s):  
Multidisciplinary Treatment ◽  
The United States ◽  
Behavioural Therapy ◽  
Lifestyle Changes ◽  
Chronic Illnesses ◽  
Therapeutic Interventions ◽  
Prevalence Studies ◽  
American College Of Rheumatology ◽  
Pain Prevalence ◽  
The Central Nervous System

Fibromyalgia is a condition with widespread muscle pain. Prevalence studies showed that 2% to 7% of the population have fibromyalgia, which affects approximately one million Canadians. Fibromyalgia is most common in women, but it also involves men and children. As with most chronic illnesses, the causes of fibromyalgia are unknown. However, recent research supports underlying abnormalities in the central nervous system, which supports fibromyalgia as a chronic disease state and valid clinical entity. Pain is the primary symptom, often accompanied by overwhelming fatigue, sleep dysfunction and cognitive impairment. In 1990, the American College of Rheumatology developed diagnostic criteria for the diagnosis of fibromyalgia. Lifestyle changes, including pacing of activities and aerobic exercise, are very important in managing fibromyalgia symptoms. Emotional and behavioural therapy can also be helpful. Controlled trials of antidepressants, gabapentinoids, tramadol, zopiclone and sodium oxybate have shown effectiveness in fibromyalgia patients. Pregabalin and duloxetine were recently approved in the United States. Effective management of fibromyalgia is complex and requires a multidisciplinary treatment approach. Response and tolerance of different therapeutic interventions vary from patient to patient. Recent advances in the pathophysiology of fibromyalgia offer hope for new and improved therapies in the management of this disabling condition.

scholarly journals Systematic Review of Studies on Telomere Lengths in Patients with Multiple Sclerosis

2020 ◽  
Author(s):  
Jan Bühring ◽  
Michael Hecker ◽  
Brit Fitzner ◽  
Uwe Klaus Zettl
Keyword(s):  
Multiple Sclerosis ◽  
Meta Analysis ◽  
Individual Variability ◽  
Biological Aging ◽  
Specific Cell ◽  
List Type ◽  
Healthy Controls ◽  
Telomere Attrition ◽  
Related Disease ◽  
Age Related

AbstractBACKGROUNDTelomeres are protective cap structures at the end of chromosomes that are essential for maintening genomic stability. Accelerated telomere shortening is related to premature cellular senescence. Shortened telomere lengths (TL) have been implicated in the pathogenesis of various chronic immune-mediated and neurological diseases.OBJECTIVEWe aimed to systematically review the current literature on the association of TL as a measure of biological age and multiple sclerosis (MS).METHODSA comprehensive literature search was conducted to identify original studies that presented data on TL in samples from MS patients. Quantitative and qualitative information was extracted from the articles to summarize and compare the studies.RESULTSA total of 51 articles were screened, and 7 of them were included in this review. In 6 studies, average TL were analyzed in peripheral blood cells, whereas in one study, bone marrow-derived cells were used. Four of the studies reported significantly shorter leukocyte TL in at least one MS subtype in comparison to healthy controls (p=0.003 in meta-analysis). Shorter telomeres in MS patients were found to be associated, independently of age, with greater disability, lower brain volume, increased relapse rate and more rapid conversion from relapsing to progressive MS. However, it remains unclear how telomere attrition in MS may be linked to oxidative stress, inflammation and age-related disease processes.CONCLUSIONSDespite few studies in this field, there is substantial evidence on the association of TL and MS. Variability in TL appears to reflect heterogeneity in clinical presentation and course. Further investigations in large and well-characterized cohorts are warranted. More detailed studies on TL of individual chromosomes in specific cell types may help to gain new insights into the pathomechanisms of MS.HighlightsThe relationship between aging and the pathophysiology and course of MS is not fully understoodWe have identified seven studies that analyzed telomere lengths (TL) in patients with MSOur meta-analysis revealed significantly shorter leukocyte TL in MS patients compared to healthy controlsThere is evidence that individual variability in biological aging reflects clinical heterogeneity in MSThe potential use of TL as a biomarker of age-related disease mechanisms deserves further investigation

scholarly journals Neurofilament light chain in the assessment of patients with multiple sclerosis

2019 ◽  
Vol 77 (6) ◽  
pp. 436-441 ◽  
Author(s):  
Renan Barros DOMINGUES ◽  
Gustavo Bruniera Peres FERNANDES ◽  
Fernando Brunale Vilela de Moura LEITE ◽  
Carlos SENNE
Keyword(s):  
Multiple Sclerosis ◽  
Axonal Degeneration ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Resonance Imaging ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
The Central Nervous System ◽  
New Biomarkers ◽  
Therapeutic Decision Making

ABSTRACT Multiple sclerosis (MS) is an autoimmune, inflammatory, and degenerative disease of the central nervous system. Axonal degeneration is triggered by inflammation and is the pathological substrate of progressive disability in patients with MS. Therapeutic interventions can reduce inflammatory activity, thus delaying neurodegeneration and the progression of disability. Disease activity and neurodegeneration are assessed mainly through clinical evaluation and magnetic resonance imaging. These measures lack sensitivity and accuracy, so new biomarkers are necessary. Several markers have been studied and to date the most promising is neurofilament light (NfL), a component of the axonal cytoskeleton, which is released into cerebrospinal fluid (CSF) following axonal damage. In the present study, we review the current knowledge about CSF NfL determination in MS, clinically isolated syndrome, and radiologically isolated syndrome, and critically discuss how CSF NfL measurement may contribute to therapeutic decision-making in these patients.

scholarly journals Leukocyte Telomere Length in Patients with Multiple Sclerosis and Its Association with Clinical Phenotypes

2021 ◽  
Author(s):  
Michael Hecker ◽  
Brit Fitzner ◽  
Kathrin Jäger ◽  
Jan Bühring ◽  
Margit Schwartz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Telomere Length ◽  
Statistical Tests ◽  
Quantitative Polymerase Chain Reaction ◽  
Polymerase Chain Reaction Method ◽  
Biological Aging ◽  
Leukocyte Telomere Length ◽  
Cross Sectional ◽  
Association Analyses ◽  
Telomere Attrition

AbstractAging is a significant factor influencing the course of multiple sclerosis (MS). Accelerated telomere attrition is an indicator of premature biological aging and a potential contributor to various chronic diseases, including neurological disorders. However, there is currently a lack of studies focusing on telomere lengths in patients with MS. We measured the average leukocyte telomere length (LTL) in biobanked DNA samples of 40 relapsing-remitting MS patients (RRMS), 20 primary progressive MS patients (PPMS), and 60 healthy controls using a multiplex quantitative polymerase chain reaction method. Changes in LTL over a period of >10 years were evaluated in a subset of 10 patients. Association analyses of baseline LTL with the long-term clinical profiles of the patients were performed using inferential statistical tests and regression models adjusted for age and sex. The cross-sectional analysis revealed that the RRMS group was characterized by a significantly shorter relative LTL, on average, as compared to the PPMS group and controls. Shorter telomeres at baseline were also associated with a higher conversion rate from RRMS to secondary progressive MS (SPMS) in the 10-year follow-up. The LTL decrease over time was similar in RRMS patients and PPMS patients in the longitudinal analysis. Our data suggest a possible contributory role of accelerated telomere shortening in the pathobiology of MS. The interplay between disease-related immune system alterations, immunosenescence, and telomere dynamics deserves further investigation. New insights into the mechanisms of disease might be obtained, e.g., by exploring the distribution of telomere lengths in specific blood cell populations.

Cold-induced reactivity in multiple sclerosis patients

2017 ◽  
pp. 56-62 ◽  
Author(s):  
Л.И. Герасимова-Мейгал ◽  
И.М. Сиренев
Keyword(s):  
Multiple Sclerosis ◽  
Cold Test ◽  
Typical Feature ◽  
Humid Climate ◽  
Ssr Analysis ◽  
Epidemiological Surveys ◽  
The Central Nervous System ◽  
The Individual ◽  
Hands And Feet ◽  
Multiple Sclerosis Patients

Цель исследования - изучение особенностей восприимчивости пациентов с рассеянным склерозом (РС) к холодовому воздействию с помощью функциональных тестов, характеризующих функцию терморегуляции. Как известно, РС - хроническое прогрессирующее аутоиммунное заболевание центральной нервной системы мультифакториальной природы, более часто встречающееся в регионах с холодным и влажным климатом. Нарушения терморегуляции вследствие автономной дисфункции являются характерным признаком РС, вместе с тем участию холодового фактора в развитии заболевания не придается существенного значения. Методика. Обследовано 32 пациента (17 мужчин и 15 женщин, средний возраст 29,6 ± 4,2 года) с установленным диагнозом: РС ремиттирующе-рецидивирующая форма течения (средняя продолжительность заболевания - 4,2 ± 2,7 года) и 18 практически здоровых лиц группы сравнения. Восприятие холода оценивали с помощью визуально-аналоговой шкалы. Продолжительность холод-индуцированной вазоконстрикции после локального холодового теста изучали по данным инфракрасной термометрии. Вегетативную регуляцию вазомоторных реакций оценивали по результатам анализа вызванных кожных вегетативных потенциалов (ВКВП). Результаты. На основе анализа самооценки восприятия холода у пациентов с РС показана низкая переносимость холодового фактора. При проведении локального холодового теста отмечено замедление восстановления температуры кожи кисти, что характерно для усиления холод-индуцированной вазоконстрикции. В группе пациентов с РС выявлено снижение параметров ВКВП ладоней и стоп, свидетельствующее о дефиците нейрогенного контроля терморегуляционных сосудистых реакций. Заключение. У пациентов с РС выявлены нарушения механизмов терморегуляции при действии холода, что обусловливает высокую индивидуальную восприимчивость к холоду у данной категории лиц. Сопоставление результатов анализа механизмов индивидуальной холод-индуцированной реактивности у пациентов с РС с данными эпидемиологических исследований приводит к заключению о потенциальном модулирующем влиянии холодового фактора на течение РС. The purpose of the present study was focused on the evaluation of the sensitivity to cold in multiple sclerosis (MS) patients by means of functional thermoregulatory based tests. MS is known to be a chronic autoimmune progressive disease of the central nervous system of multifactor origin that is very common in regions with cold and humid climate. Disorder of thermoregulation caused by autonomic dysfunction is a typical feature of MS, however the role of the cold in the disease development is still underestimated. Methods. Thirty two MS patients (17 males, 15 females, mean age 29,6 ± 4,2 years) with the remittent form of the disease (mean disease duration 4,2 ± 2,7 years) and 18 age-matched healthy controls volunteered to participate in this study. Susceptibility to cold was analyzed with the use of visual-analogous scale. The duration of cold-induced vasoconstriction after local cold test was estimated using by infrared thermometry. Autonomic regulation of vasomotor reactions was investigated with the help of the skin sympathetic response (SSR) analysis. Results. The analysis of self-reported perception of the cold in MS patients showed their low tolerance to cold. Slow recovery of the skin temperature of the hand in the local cold test observed in MS patients was considered as the aggravated cold-induced vasoconstriction. The decreased SSR in the hands and feet in MS patients was found that indicates the deficit of the neurogenic control of thermoregulatory vasomotor reactions. Conclusion. The results obtained demonstrate the impairment of thermoregulation under cold in MS patients that leads to higher individual susceptibility to cold of this group. Comparing of the data found in this study on the mechanisms of the individual cold-induced reactivity in MS patients with epidemiological surveys enable to conclude that cold environment has potential modulating effect of on the course of MS.

Immunomodulation in Multiple Sclerosis by Phytotherapy

2020 ◽  
Vol 16 (1) ◽  
pp. 28-36
Author(s):  
Maryam Bahrami ◽  
Ghasem Mosayebi ◽  
Ali Ghazavi ◽  
Ali Ganji
Keyword(s):  
Multiple Sclerosis ◽  
Nigella Sativa ◽  
Boswellia Serrata ◽  
Immunomodulatory Agents ◽  
Therapeutic Benefits ◽  
Demyelinating Disorder ◽  
Sensory Impairments ◽  
The Central Nervous System ◽  
Pomegranate Peel Extract ◽  
Peel Extract

Multiple sclerosis is a chronic inflammatory and demyelinating disorder of the central nervous system (CNS) that can cause cognition, mobility, and sensory impairments. Studies have shown that the immune system through inflammation and autoreactive T cells are involved in the progression of MS. The present article aimed to review the potent anti-inflammatory, antioxidant, and immunomodulatory agents that could modulate the immune response in MS. In herbal medicine, various medicinal plants including Olive, Silybum marianum, Grape, Pomegranate peel extract, Nigella sativa, Turmeric, Green tea, Aloysia citrodora, Boswellia papyrifera, Boswellia serrata, Ruta graveolens, and Andrographis paniculata are known with therapeutic benefits in MS patients through immunoregulation and reduction of major symptoms.

The Effects of Different Kinds of Nutrition and Functional Foods on Multiple Sclerosis

2020 ◽  
Vol 16 (5) ◽  
pp. 632-637
Author(s):  
Masih Falahatian
Keyword(s):  
Multiple Sclerosis ◽  
Functional Foods ◽  
Fruits And Vegetables ◽  
Salt Intake ◽  
Vegetable Intake ◽  
Dietary Salt ◽  
Negative Effects ◽  
Dietary Salt Intake ◽  
Neuroinflammatory Disease ◽  
The Central Nervous System

It is an assumption that different kinds of nutrition, diet, and functional foods might have different positive or negative effects on multiple sclerosis (MS), a neuroinflammatory disease of the central nervous system (CNS). This brief paper involved a study on various kinds of nutrition including salt, fat, dairy, fruit, and vegetables. At the end of this study, appropriate diets were evaluated for MS patients. Based on previous studies both on animal models and on MS patients, excessive dietary salt intake and animal fat had worsening effects on MS patients but fruit and vegetable intake helped the remission of MS and decreased the risk of developing it. There were, of course, conflicting results in different studies over the role of some nutrition in MS and future studies on larger numbers of cases were required to collect reliable results. As a result, at the end of this study and based on literature, it is suggested that a diet should be programmed by nutritionists containing fewer salt, fat, and dairy intake and more fruits and vegetables for MS patients in order to better management of the disease.

scholarly journals Neural Stem Cells: What Happens When They Go Viral?

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1468
Author(s):  
Yashika S. Kamte ◽  
Manisha N. Chandwani ◽  
Alexa C. Michaels ◽  
Lauren A. O’Donnell
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Viral Infections ◽  
Wide Spectrum ◽  
Cell Types ◽  
Developmental Abnormalities ◽  
Multipotent Progenitor Cells ◽  
The Central Nervous System ◽  
Simplex Virus ◽  
The Brain

Viruses that infect the central nervous system (CNS) are associated with developmental abnormalities as well as neuropsychiatric and degenerative conditions. Many of these viruses such as Zika virus (ZIKV), cytomegalovirus (CMV), and herpes simplex virus (HSV) demonstrate tropism for neural stem cells (NSCs). NSCs are the multipotent progenitor cells of the brain that have the ability to form neurons, astrocytes, and oligodendrocytes. Viral infections often alter the function of NSCs, with profound impacts on the growth and repair of the brain. There are a wide spectrum of effects on NSCs, which differ by the type of virus, the model system, the cell types studied, and the age of the host. Thus, it is a challenge to predict and define the consequences of interactions between viruses and NSCs. The purpose of this review is to dissect the mechanisms by which viruses can affect survival, proliferation, and differentiation of NSCs. This review also sheds light on the contribution of key antiviral cytokines in the impairment of NSC activity during a viral infection, revealing a complex interplay between NSCs, viruses, and the immune system.

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