scholarly journals Telomere length and age-dependent telomere attrition: the blood-and-muscle model

2019 ◽  
Vol 97 (4) ◽  
pp. 328-334 ◽  
Author(s):  
Mirna N. Chahine ◽  
Simon Toupance ◽  
Sandy El-Hakim ◽  
Carlos Labat ◽  
Sylvie Gautier ◽  
...  

Short telomere length (TL) is associated with atherosclerotic cardiovascular disease (ACVD) and other age-related diseases. It is unclear whether these associations originate from having inherently short TL or a faster TL attrition before or during disease development. We proposed the blood-and-muscle model to assess TL dynamics throughout life course. Our objective was to measure TL in leukocytes (LTL) and in skeletal muscle (MTL), which served as a proxy of TL at birth. The delta (MTL–LTL) represented life-long telomere attrition. Blood draws and skeletal muscle biopsies were performed on 35 Lebanese individuals undergoing surgery. Following DNA extraction, LTL and MTL were measured by Southern blot. In every individual aged between 30 and 85 years, MTL was longer than LTL. With age, MTL and LTL decreased, but the delta (MTL–LTL) increased by 14 bp/year. We validated the blood-and-muscle model that allowed us to identify TL, TL at birth, and lifelong TL attrition in a cross-sectional study. This model can be used in larger cross-sectional studies to evaluate the association of telomere dynamics with age-related diseases onset and progression.

BMJ Open ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. e034226
Author(s):  
Lei Feng ◽  
Shiyan Nian ◽  
Zongwu Tong ◽  
Ying Zhu ◽  
Ying Li ◽  
...  

ObjectivesThis study aimed to investigate the dynamic trends in total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels with ageing.DesignA Chinese population-based cross-sectional study.SettingA physical examination centre of a general hospital.ParticipantsAdult subjects (178 167: 103 461 men and 74 706 women) without a known medical history or treatments that affect lipid metabolism.Main outcome measuresDynamic trends in the above-mentioned lipid parameters with ageing were explored; turning points of age were established using age stratification and validated by fitted multivariate linear regression modelling.ResultsAge was found to be an independent factor extensively associated with lipid levels in both sexes when adjusted for serum glucose, body mass index, lifestyle, drinking and smoking. Age was positively associated with TC, logarithm-transformed TG (LnTG) and LDL-C levels in men ≤40, ≤40 and ≤60 years old (yo) and in women ≤60, ≤70 and ≤60 yo, respectively. Conversely, age correlated negatively with TC, LnTG and LDL-C levels in men ≥61, ≥41 and ≥61 yo and in women ≥61, ≥71 and ≥61 yo, respectively. TC, TG and LDL-C levels in women were initially lower than those in men but surpassed those in men in 51–55, 61–65 and 51–55 yo age groups. The trends in HDL-C levels with age were relatively irregular, although HDL-C levels in women were higher than in men for all age groups.ConclusionsThe definition of dyslipidaemia, the atherosclerotic cardiovascular disease risk assessment and the initiation/goals of statin therapy should fully consider age-related trends in lipid levels and sex differences.


2019 ◽  
Vol 98 (8) ◽  
pp. 857-862 ◽  
Author(s):  
Olga A. Vyatleva ◽  
A. M. Kurgansky

Introduction. The broad spread of cell phones (CP) among schoolchildren and the absence of age standards for their safe use determined the purpose of the study: to reveal the regimens of CP use, critical for the health of children and adolescents. Material and methods. In a cross-sectional study in 2008-2010, by the questionnaire data of 2,137 schoolchildren aged 6-15 years there was assessed the impact of CP usage indices (daily number of calls - CN, call duration - CD, and total daily duration of calls - TCDD) on health (the incidence of headaches and sleep disorders, number of colds). Student and Mann-Whitney criteria and assessment of relative risks were used. Results. The study revealed age-dependent critical values of usage indices (in 6-10 years: CN=2, TCDD=6 minutes.; in 11-13 years: CN=6; in 14-15 years CN=6, CD=3 minutes., TCDD=4 -10 min.), the exceeding of which due to risks: in 6-10 years - to have more than 4 colds a year (OR 2.25, 95% CI 1.09-4.62); in 11-13 years to have several headaches per week (OR 1.61, 95% CI 1.12-2.30); in 14-15 years - to have several headaches (OR 1.79, 95% CI 1.27-2.54) and several sleep disorders (OR 1.66, 95% CI 1.17-2.37) per week. Discussion. Age differences in critical modes of CP use and in health violations, as well as the importance of radiation intensity are discussed. Conclusions. Age-related CP use regimens, critical for health, were established. It was shown the need to develop more precise age criteria for safe CP use with taking into account a wider range of health indicators and radiation intensity.


BMJ Open ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. e032513 ◽  
Author(s):  
Mirko Manchia ◽  
Pasquale Paribello ◽  
Carlo Arzedi ◽  
Alberto Bocchetta ◽  
Paola Caria ◽  
...  

IntroductionSevere psychiatric disorders are typically associated with a significant reduction in life expectancy compared with the general population. Among the different hypotheses formulated to explain this observation, accelerated ageing has been increasingly recognised as the main culprit. At the same time, telomere shortening is becoming widely accepted as a proxy molecular marker of ageing. The present study aims to fill a gap in the literature by better defining the complex interaction/s between inflammation, age-related comorbidities, telomere shortening and gut microbiota in psychiatric disorders.Methods and analysisA cross-sectional study is proposed, recruiting 40 patients for each of three different diagnostic categories (bipolar disorder, schizophrenia and major depressive disorder) treated at the Section of Psychiatry and at the Unit of Clinical Pharmacology of the University Hospital Agency of Cagliari (Italy), compared with 40 age-matched and sex-matched non-psychiatric controls. Each group includes individuals suffering, or not, from age-related comorbidities, to account for the impact of these medical conditions on the biological make-up of recruited patients. The inflammatory state, microbiota composition and telomere length (TL) are assessed.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the University Hospital Agency of Cagliari (PG/2018/11693, 5 September 2018). The study is conducted in accordance with the principles of good clinical practice and the Declaration of Helsinki, and in compliance with the relevant Italian national legislation. Written, informed consent is obtained from all participants. Participation in the study is on a voluntary basis only. Patients will be part of the dissemination phase of the study results, during which a local conference will be organised and families of patients will also be involved. Moreover, findings will be published in one or more research papers and presented at national and international conferences, in posters or oral communications.


Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1360
Author(s):  
Simon Toupance ◽  
Maria G. Stathopoulou ◽  
Alexandros M. Petrelis ◽  
Vesna Gorenjak ◽  
Carlos Labat ◽  
...  

Short leukocyte telomere length (LTL) is associated with atherosclerotic cardiovascular disease (ASCVD). Mendelian randomisation studies, using single nucleotide polymorphisms (SNPs) associated with short LTL, infer a causal role of LTL in ASCVD. Recent results, using the blood-and-muscle model, indicate that higher early life LTL attrition, as estimated by the ratio between LTL and skeletal muscle telomere length (MTL), rather than short LTL at conception, as estimated by MTL, should be responsible of the ASCVD-LTL connection. We combined LTL and MTL measurements and SNPs profiling in 402 individuals to determine if 15 SNPs classically described as associated with short LTL at adult age were rather responsible for higher LTL attrition during early life than for shorter LTL at birth. Two of these SNPs (rs12696304 and rs10936599) were associated with LTL in our cohort (p = 0.027 and p = 0.025, respectively). These SNPs, both located on the TERC gene, were associated with the LTL/MTL ratio (p = 0.007 and p = 0.037, respectively), but not with MTL (p = 0.78 and p = 0.32 respectively). These results suggest that SNPs located on genes coding for telomere maintenance proteins may contribute to a higher LTL attrition during the highly replicative first years of life and have an impact later on the development of ASCVD.


Author(s):  
Samuel S. Aguiar ◽  
Thiago S. Rosa ◽  
Rodrigo V. P. Neves ◽  
Patrício L. A. Leite ◽  
Larissa A. Maciel ◽  
...  

AbstractLower SIRT1 and insulin resistance are associated with accelerated telomere shortening. This study investigated whether the lifestyle of master athletes can attenuate these age-related changes and thereby slow aging. We compared insulin, SIRT1, and telomere length in highly trained male master athletes (n=52; aged 49.9±7.2 yrs) and age-matched non-athletes (n=19; aged 47.3±8.9 yrs). This is a cross-sectional study, in which all data were collected in one visit. Overnight fasted SIRT1 and insulin levels in whole blood were assessed using commercial kits. Relative telomere length was determined in leukocytes through qPCR analyses. Master athletes had higher SIRT1, lower insulin, and longer telomere length than age-matched non-athletes (p<0.05 for all). Insulin was inversely associated with SIRT1 (r=−0.38; p=0.001). Telomere length correlated positively with SIRT1 (r=0.65; p=0.001), whereas telomere length and insulin were not correlated (r=0.03; p=0.87). In conclusion, master athletes have higher SIRT1, lower insulin, and longer telomeres than age-matched non-athletes. Furthermore, SIRT1 was negatively associated with insulin and positively associated with telomere length. These findings suggest that in this sample of middle-aged participants reduced insulin, increased SIRT1 activity, and attenuation of biological aging are connected.


2019 ◽  
Vol 6 (6) ◽  
pp. 190420 ◽  
Author(s):  
Melissa Bateson ◽  
Abraham Aviv ◽  
Laila Bendix ◽  
Athanase Benetos ◽  
Yoav Ben-Shlomo ◽  
...  

Smoking is associated with shorter leucocyte telomere length (LTL), a biomarker of increased morbidity and reduced longevity. This association is widely interpreted as evidence that smoking causes accelerated LTL attrition in adulthood, but the evidence for this is inconsistent. We analysed the association between smoking and LTL dynamics in 18 longitudinal cohorts. The dataset included data from 12 579 adults (4678 current smokers and 7901 non-smokers) over a mean follow-up interval of 8.6 years. Meta-analysis confirmed a cross-sectional difference in LTL between smokers and non-smokers, with mean LTL 84.61 bp shorter in smokers (95% CI: 22.62 to 146.61). However, LTL attrition was only 0.51 bp yr −1 faster in smokers than in non-smokers (95% CI: −2.09 to 1.08), a difference that equates to only 1.32% of the estimated age-related loss of 38.33 bp yr −1 . Assuming a linear effect of smoking, 167 years of smoking would be required to generate the observed cross-sectional difference in LTL. Therefore, the difference in LTL between smokers and non-smokers is extremely unlikely to be explained by a linear, causal effect of smoking. Selective adoption, whereby individuals with short telomeres are more likely to start smoking, needs to be considered as a more plausible explanation for the observed pattern of telomere dynamics.


2021 ◽  
pp. 247412642198922
Author(s):  
Brittany C. Tsou ◽  
T.Y. Alvin Liu ◽  
Jun Kong ◽  
Susan B. Bressler ◽  
J. Fernando Arevalo ◽  
...  

Purpose: This work evaluated the use and type of dietary supplements and home monitoring for nonneovascular age-related macular degeneration (AMD), as well as the prevalence of genetic testing among patients with AMD. Methods: A cross-sectional study was conducted of 129 participants older than 50 years who completed self-administered questionnaires regarding usage and type of dietary supplements and home monitoring, as well as the participants’ use of genetic testing for AMD. Results: Of 91 participants with AMD, 83 (91.2%) took vitamins, including 55 (60.4%) who used an Age-Related Eye Disease Study (AREDS) or AREDS2 formulation. Of 38 without AMD, 31 (81.6%) took vitamins (difference from participants with AMD = 9.6% [95% CI, 0%-23.2%]), including 2 on an AREDS formulation. Among 82 participants with AMD who were AREDS candidates (intermediate or advanced AMD in 1 or both eyes), 51 (62.2%; 95% CI, 51.7%-72.7%) took an AREDS or AREDS2 formulation, and 31 (37.8%) did not (5 were unsure). Additionally, 50 (61.0%; 95% CI, 50.4%-71.6%) AREDS candidates did some type of home monitoring. Only 1 (1.2%; 95% CI, 0%-3.6%) underwent genetic testing for AMD. Among 9 with AMD who were not AREDS candidates, 4 (44.4%) used an AREDS formulation, 4 (44.4%) did not, and 1 (11.1%) was unsure; only 1 (11.1%) of these 9 performed home monitoring. Conclusions: Despite similar results from past surveys and AREDS2 data supporting supplement use in 2013 and home monitoring in 2014, these findings suggest about one-third of AREDS candidates do not do so, providing further support for improving education regarding appropriate supplement and home monitoring usage. Genetic testing for AMD also appears infrequent.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1160.2-1161
Author(s):  
I. Fairushina ◽  
D. Abdulganieva ◽  
E. Kirillova ◽  
R. Abdrakipov

Background:Detection of subclinical enthesitis and synovitis in psoriatic arthritis (PsA) is prevalent and ultrasound (US) examination is informative tool for it diagnosing. Aging positively affects degenerative changes.Objectives:To study relationship between US articular and entheseal findings with age in patients with PsA.Methods:57 patients were enrolled to study with fulfilled PsA criteria (CASPAR, 2009). Data collection: demographical, clinical (current psoriasis, axial involvement, enthesitis, dactylitis), US (synovitis count (by Grey Scale), Power Doppler(PD)+ synovitis), thickening and hypoechogenicity at enthesis, PD+ enthesitis, entheses with structural components); biological (high sensitive C-reactive protein (hsCRP), Erythrocyte Sedimentation Rate (ESR).US examination included 798 joints and 3078 entheses (bilateral shoulders, acromioclavicular joints, elbows, wrists, hips, knees, ankles; entheses at the projection of these joints (total number - 54). US entheseal findings were fixed according to consensus-based US definition and scoring for enthesitis in spondyloarthritis and PsA (OMERACT US)1.Results:In all 57 patients: male - 25 (43.9%), mean age 43.4±10.3(SD) years (y), PsA duration was 7 (3;10) y, Ps duration 10 (8; 22) y; 53 (41.1%) had axial involvement, 42 (73.7%) dactylitis, 8 (14%) clinical enthesitis, and 56 (98.2 %) skin psoriasis, Psoriasis Activity and Severity Index score 6.4 (2;14.4), Disease Activity in PsA score 18.1 (10.2;26.1), hsCRP 10.1(2.4;21.4), ESR 20 (11.3;31.5).Synovitis count increased with age noticeably (r=0.508, p<0.01), and weak correlation of PD+ synovitis (r=0.262, p=0.049) and age was found. The entheseal thickening and hypoechogenicity and structural findings increased with age respectively (r=0.345, p=0.009; r=0.337, p=0.01). There was no correlation between PD+ enthesitis and age. The assosiation between PD+ enthesitis and blood biomarkers of inflammation (hs-CRP (r=0.364, p=0.008); ESR (p=0.358, p=0.008) was found.Conclusion:Our study found significant relationship between age and US synovitis. Association between age and US entheseal involvement was noted. Only PD+ enthesitis was not related with age in comparison with other US entheseal findings. The presence of PD US signal at enthesitis in association with increased inflammatory blood biomarkers can be evaluated as the sign of disease activity regardless of age and not as age-related lesion in PsA patients.References:[1]Balint PV, Terslev L, Aegerter P et al. Reliability of a consensus-based ultrasound definition and scoring for enthesitis in spondyloarthritis and psoriatic arthritis: an OMERACT US initiative. Ann Rheum Dis.;2018;77(12):1730-1735.Disclosure of Interests:None declared


Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 183
Author(s):  
Kevin M Mendez ◽  
Janice Kim ◽  
Inês Laíns ◽  
Archana Nigalye ◽  
Raviv Katz ◽  
...  

The purpose of this study was to analyze the association between plasma metabolite levels and dark adaptation (DA) in age-related macular degeneration (AMD). This was a cross-sectional study including patients with AMD (early, intermediate, and late) and control subjects older than 50 years without any vitreoretinal disease. Fasting blood samples were collected and used for metabolomic profiling with ultra-performance liquid chromatography–mass spectrometry (LC-MS). Patients were also tested with the AdaptDx (MacuLogix, Middletown, PA, USA) DA extended protocol (20 min). Two measures of dark adaptation were calculated and used: rod-intercept time (RIT) and area under the dark adaptation curve (AUDAC). Associations between dark adaption and metabolite levels were tested using multilevel mixed-effects linear modelling, adjusting for age, gender, body mass index (BMI), smoking, race, AMD stage, and Age-Related Eye Disease Study (AREDS) formulation supplementation. We included a total of 71 subjects: 53 with AMD (13 early AMD, 31 intermediate AMD, and 9 late AMD) and 18 controls. Our results revealed that fatty acid-related lipids and amino acids related to glutamate and leucine, isoleucine and valine metabolism were associated with RIT (p < 0.01). Similar results were found when AUDAC was used as the outcome. Fatty acid-related lipids and amino acids are associated with DA, thus suggesting that oxidative stress and mitochondrial dysfunction likely play a role in AMD and visual impairment in this condition.


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