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 Identifying Significant Biological Markers in Klotho Gene Variants Across Wide Ranging Taxonomy

2015 ◽  
Vol 5 (1) ◽  
pp. 11
Author(s):  
Tommy Rodriguez
Keyword(s):  
Transmembrane Protein ◽  
Genetic Regulation ◽  
Comparative Sequence Analysis ◽  
Biological Aging ◽  
Altered State ◽  
Telomere Attrition ◽  
Related Disease ◽  
Age Related ◽  
Evolutionary Context ◽  
Klotho Protein

<p class="1Body">Biological aging is marked by progressively degenerative physiological change that causes damage to tissues and organs. Errors in biopolymers accumulate over time; mitochondrial dysfunction, telomere attrition, and wider genomic instability lead to an altered state of intercellular communication. In this investigation, my focus will be aimed at examining and identifying specifically critical biomarkers in genetic variants of KLOTHO (a transmembrane protein involved in the genetic regulation of age-related disease) among organisms with varied life spans that range across wide taxonomical rankings. Here, I investigate the correlation between lower and higher frequency a-amino acid compositions in Klotho protein factors within a grouped methodology; as to also include several demonstrative techniques in comparative sequence analysis for inferring relatedness in evolutionary context.</p>

Association between circulating leptin levels and multiple sclerosis: a systematic review and meta-analysis

2018 ◽  
Vol 94 (1111) ◽  
pp. 278-283 ◽  
Author(s):  
Xue-Feng Xie ◽  
Xiao-Hui Huang ◽  
Ai-Zong Shen ◽  
Jun Li ◽  
Ye-Huan Sun
Keyword(s):  
Multiple Sclerosis ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Control Group ◽  
Sample Type ◽  
Healthy Controls ◽  
Eligibility Criteria ◽  
Effect Model ◽  
Healthy Control

AimLeptin, synthesised by adipocytes, has been identified as a hormone that can influence inflammatory activity. Several studies have investigated leptin levels in patients with multiple sclerosis (MS), but the results are not consistent. This study aims to derive a more precise evaluation on the relationship between circulating leptin levels and MS.DesignA comprehensive literature searched up to July 2017 was conducted to evaluate the association of circulating leptin levels and MS. The random-effect model was applied to calculate pooled standardised mean difference (SMD) and its 95% CI.Main outcome measuresCirculating leptin levels of patients with MS and healthy controls.ResultsOf 2155 studies identified, 33 met eligibility criteria and 9 studies with 645 patients with MS and 586 controls were finally included in the meta-analysis. Meta-analysis revealed that, compared with the healthy control group, the MS group had significantly higher plasma/serum leptin levels, with the SMD of 0.70% and 95% CI (0.24 to 1.15). Subgroup analyses suggested that the leptin levels of patients with MS were associated with region, age, study sample size, measurement type, gender and blood sample type.ConclusionOverall, our study suggests that patients with MS have a significantly higher leptin level than in healthy controls. Further mechanism studies and longitudinal large cohort studies are still needed to further reveal the role of leptin in the pathogenesis of MS.

scholarly journals Chronological age, biological age, and individual variation in the stress response in the European starling: A follow-up study

2018 ◽  
Author(s):  
Annie Gott ◽  
Clare Andrews ◽  
Maria Larriva Hormigos ◽  
Karen Spencer ◽  
Melissa Bateson ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Biological Age ◽  
Chronological Age ◽  
Stress System ◽  
Telomere Attrition ◽  
Follow Up Study ◽  
Age Related ◽  
Stress Responsiveness ◽  
Individual Consistency

The responsiveness of the avian stress system declines with age. A recently published study of European starlings (Sturnus vulgaris) found that a marker of biological age predicted stress responsiveness even in individuals of the same chronological age. Specifically, birds that had experienced greater developmental telomere attrition showed a lower peak corticosterone response to an acute stressor, and more rapid recovery of corticosterone levels towards baseline. Here, we performed a follow-up study using the same capture-restraint-handling stressor in a separate cohort of 27 starlings. Unlike the original study, we measured the response at two different age points (4 and 18 months). We did not replicate the associations with developmental telomere attrition observed in the previous study at either age point. However, a meta-analysis of the present results combined with those of the earlier study still lent some support to the conclusions of the earlier paper. Estimates of familial influence on stress responsiveness differed across the two age points. We found little evidence of individual consistency in stress responsiveness between 4 and 18 months. Peak corticosterone was significantly lower at the second age point than the first, though interpretation of this as age-related decline is problematic due to the samples having been analysed at different times.

Reactive Balance Adaptability and Retention in People With Multiple Sclerosis: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 34 (8) ◽  
pp. 675-685
Author(s):  
Mohamed Suhair Bin Mohamed Suhaimy ◽  
Yoshiro Okubo ◽  
Phu D. Hoang ◽  
Stephen R. Lord
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Response Times ◽  
Balance Control ◽  
Meta Analysis ◽  
Healthy Controls ◽  
Functional Impairments ◽  
Training Effects ◽  
Meta Analyses ◽  
Reactive Balance

Aim. To compare reactive balance in people with multiple sclerosis (MS) with healthy controls and to examine the ability of people with MS to adapt their reactive balance and retain training effects. Data Sources. Electronic databases (PubMed, EMBASE, PsychINFO) and reference lists of included articles from inception to February 25, 2019. Study Selection. Case-control and intervention studies that assessed reactive balance using mechanical perturbations in people with a confirmed diagnosis of MS. Results. Meta-analyses of 9 studies (n = 342) showed that people with MS have significantly worse reactive balance than healthy controls (standardized mean difference [SMD] 0.78, 95% CI 0.44-1.11, P < .0001, I2 = 47%). Specifically, people with MS have greater center of mass displacements (SMD 0.41, 95% CI 0.05-0.77, P = .02, I2 = 9%) and longer response times (MD (ms) 31.45, 95% CI 19.91-42.98, P < .0001, I2 = 75%) in response to standing perturbations than healthy controls. Subsequent meta-analyses revealed training comprising repeated exposure to perturbations improved response times ( P < .001) and training effects on response times could be retained for 24 hours ( P < .001) in people with MS. Conclusions. Reactive balance assessments can highlight functional impairments related to falls in people with MS, and perturbation training can acutely improve reactive balance control and such improvements can be retained for 24 hours in this population. Systematic review registration number: CRD42019126130.

scholarly journals Synapse-selective control of cortical maturation and plasticity engages an interneuron-autonomous synaptic switch

2018 ◽  
Author(s):  
Adema Ribic ◽  
Michael C. Crair ◽  
Thomas Biederer
Keyword(s):  
Visual Cortex ◽  
Critical Period ◽  
Visual Experience ◽  
Cortical Plasticity ◽  
Brain Plasticity ◽  
Cortical Inhibition ◽  
Specific Cell ◽  
List Type ◽  
Critical Periods ◽  
Age Related

HighlightsThe synaptogenic molecule SynCAM 1 is selectively regulated by visual experienceSynCAM 1 controls thalamic input onto cortical Parvalbumin (PV+) interneuronsPV+-specific knockdown of SynCAM 1 arrests maturation of cortical inhibitionThalamic excitation onto PV+ interneurons is essential for critical period closureeTOC BlurbRibic et al. show that network plasticity in both young and adult cortex is restricted by the synapse organizing molecule SynCAM 1. On a cellular level, it functions in Parvalbumin-positive interneurons to recruit thalamocortical terminals. This controls the maturation of inhibitory drive and restricts plasticity in the cortex. These results reveal the synaptic locus of cortical plasticity and identify the first cell-autonomous synaptic factor for closure of cortical critical periods.SummaryBrain plasticity peaks early in life and tapers in adulthood. This is exemplified in the primary visual cortex, where brief loss of vision to one eye abrogates cortical responses to inputs from that eye during the critical period, but not in adulthood. The synaptic locus of critical period plasticity and the cell-autonomous synaptic factors timing these periods remain unclear. We here demonstrate that the immunoglobulin protein Synaptic Cell Adhesion Molecule 1 (SynCAM 1/Cadm1) is regulated by visual experience and limits visual cortex plasticity. SynCAM 1 selectively controls the number of excitatory thalamocortical (TC) inputs onto Parvalbumin (PV+) interneurons and loss of SynCAM 1 in turn impairs the maturation of TC-driven feed-forward inhibition. SynCAM 1 acts in cortical PV+ interneurons to perform these functions and its PV+-specific knockdown prevents the age-related plasticity decline. These results identify a synapse type-specific, cell-autonomous mechanism that governs circuit maturation and closes the visual critical period.

scholarly journals Cortical Thickness Trajectories across the Lifespan: Data from 17,075 healthy individuals aged 3-90 years

2020 ◽  
Author(s):  
Sophia Frangou ◽  
Amirhossein Modabbernia ◽  
Gaelle E Doucet ◽  
Efstathios Papachristou ◽  
Steven CR Williams ◽  
...  
Keyword(s):  
Cortical Thickness ◽  
Large Scale ◽  
Meta Analysis ◽  
General Pattern ◽  
Individual Variability ◽  
Anterior Cingulate ◽  
Healthy Individuals ◽  
Large Scale Analysis ◽  
Age Related ◽  
Steep Decrease

AbstractDelineating age-related cortical trajectories in healthy individuals is critical given the association of cortical thickness with cognition and behaviour. Previous research has shown that deriving robust estimates of age-related brain morphometric changes requires large-scale studies. In response, we conducted a large-scale analysis of cortical thickness in 17,075 individuals aged 3-90 years by pooling data through the Lifespan Working group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium. We used fractional polynomial (FP) regression to characterize age-related trajectories in cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma (LMS) method. Inter-individual variability was estimated using meta-analysis and one-way analysis of variance. Overall, cortical thickness peaked in childhood and had a steep decrease during the first 2-3 decades of life; thereafter, it showed a gradual monotonic decrease which was steeper in men than in women particularly in middle-life. Notable exceptions to this general pattern were entorhinal, temporopolar and anterior cingulate cortices. Inter-individual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results reconcile uncertainties about age-related trajectories of cortical thickness; the centile values provide estimates of normative variance in cortical thickness, and may assist in detecting abnormal deviations in cortical thickness, and associated behavioural, cognitive and clinical outcomes.

scholarly journals Key Signaling Pathways in Aging and Potential Interventions for Healthy Aging

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 660
Author(s):  
Mengdi Yu ◽  
Hongxia Zhang ◽  
Brian Wang ◽  
Yinuo Zhang ◽  
Xiaoying Zheng ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Mammalian Target Of Rapamycin ◽  
Adenosine Monophosphate ◽  
Sirtuin 1 ◽  
Public Health Issue ◽  
Biological Aging ◽  
Related Disease ◽  
Age Related ◽  
General Decline

Aging is a fundamental biological process accompanied by a general decline in tissue function. Indeed, as the lifespan increases, age-related dysfunction, such as cognitive impairment or dementia, will become a growing public health issue. Aging is also a great risk factor for many age-related diseases. Nowadays, people want not only to live longer but also healthier. Therefore, there is a critical need in understanding the underlying cellular and molecular mechanisms regulating aging that will allow us to modify the aging process for healthy aging and alleviate age-related disease. Here, we reviewed the recent breakthroughs in the mechanistic understanding of biological aging, focusing on the adenosine monophosphate-activated kinase (AMPK), Sirtuin 1 (SIRT1) and mammalian target of rapamycin (mTOR) pathways, which are currently considered critical for aging. We also discussed how these proteins and pathways may potentially interact with each other to regulate aging. We further described how the knowledge of these pathways may lead to new interventions for antiaging and against age-related disease.

scholarly journals Chronological age, biological age, and individual variation in the stress response in the European starling: A follow-up study

2018 ◽  
Author(s):  
Annie Gott ◽  
Clare Andrews ◽  
Maria Larriva Hormigos ◽  
Karen Spencer ◽  
Melissa Bateson ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Biological Age ◽  
Chronological Age ◽  
Stress System ◽  
Telomere Attrition ◽  
Follow Up Study ◽  
Age Related ◽  
Stress Responsiveness ◽  
Individual Consistency

The responsiveness of the avian stress system declines with age. A recently published study of European starlings (Sturnus vulgaris) found that a marker of biological age predicted stress responsiveness even in individuals of the same chronological age. Specifically, birds that had experienced greater developmental telomere attrition showed a lower peak corticosterone response to an acute stressor, and more rapid recovery of corticosterone levels towards baseline. Here, we performed a follow-up study using the same capture-restraint-handling stressor in a separate cohort of 27 starlings. Unlike the original study, we measured the response at two different age points (4 and 18 months). We did not replicate the associations with developmental telomere attrition observed in the previous study at either age point. However, a meta-analysis of the present results combined with those of the earlier study still lent some support to the conclusions of the earlier paper. Estimates of familial influence on stress responsiveness differed across the two age points. We found little evidence of individual consistency in stress responsiveness between 4 and 18 months. Peak corticosterone was significantly lower at the second age point than the first, though interpretation of this as age-related decline is problematic due to the samples having been analysed at different times.

scholarly journals A Systematic Review and Meta-analysis of Environmental, Lifestyle, and Health Factors Associated With DNA Methylation Age

2019 ◽  
Vol 75 (3) ◽  
pp. 481-494 ◽  
Author(s):  
Joanne Ryan ◽  
Jo Wrigglesworth ◽  
Jun Loong ◽  
Peter D Fransquet ◽  
Robyn L Woods
Keyword(s):  
Dna Methylation ◽  
Meta Analysis ◽  
Conclusive Evidence ◽  
Chronological Age ◽  
Biological Aging ◽  
Robust Estimate ◽  
Healthy Life ◽  
Age Related ◽  
Health Factors ◽  
Dna Methylation Age

Abstract DNA methylation (DNAm) algorithms of biological age provide a robust estimate of an individual’s chronological age and can predict their risk of age-related disease and mortality. This study reviewed the evidence that environmental, lifestyle and health factors are associated with the Horvath and Hannum epigenetic clocks. A systematic search identified 61 studies. Chronological age was correlated with DNAm age in blood (median .83, range .13–.99). In a meta-analysis body mass index (BMI) was associated with increased DNAm age (Hannum β: 0.07, 95% CI 0.04 to 0.10; Horvath β: 0.06, 95% CI 0.02 to 0.10), but there was no association with smoking (Hannum β: 0.12, 95% CI −0.50 to 0.73; Horvath β:0.18, 95% CI −0.10 to 0.46). DNAm age was positively associated with frailty (three studies, n = 3,093), and education was negatively associated with the Hannum estimate of DNAm age specifically (four studies, n = 13,955). For most other exposures, findings were too inconsistent to draw conclusions. In conclusion, BMI was positively associated with biological aging measured using DNAm, with some evidence that frailty also increased aging. More research is needed to provide conclusive evidence regarding other exposures. This field of research has the potential to provide further insights into how to promote slower biological aging and ultimately prolong healthy life.

scholarly journals DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Pamela R. Matías-García ◽  
Cavin K. Ward-Caviness ◽  
Laura M. Raffield ◽  
Xu Gao ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
African American ◽  
Kidney Disease ◽  
Meta Analysis ◽  
Methylation Status ◽  
Serum Urate ◽  
Biological Aging ◽  
Epigenetic Biomarkers ◽  
Age Related ◽  
New Findings

Abstract Background The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. Results We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E−03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang’s 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (β =  − 0.12, 95% CI = [− 0.16, − 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E−08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (β = 0.12 [0.07, 0.16], p = 2.08E−06). The “first-generation” clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria. Conclusion DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease.

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