Assessing the variability of telomere length measures by means of Telomeric Restriction Fragments (TRF) in different tissues of cod Gadus morhua

Gene Reports ◽  
2016 ◽  
Vol 5 ◽  
pp. 117-125
Author(s):  
E. Lopez de Abechuco ◽  
N. Hartmann ◽  
M. Soto ◽  
G. Díez
Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4953-4953
Author(s):  
Sweta Gupta ◽  
Sadiya Khan ◽  
Sanjiv Shah ◽  
Ekaterina Klyachko ◽  
Abigail S Baldridge ◽  
...  

Abstract Introduction: Plasminogen activator inhibitor-1 (PAI-1) is an important component of the senescence-associated secretome that contributes directly to cellular senescence. Telomeres, the nucleotide repeat structures located at the ends of chromosomes, shorten progressively with each round of cellular replication and telomere attrition is associated with cellular senescence. In murine models, genetic or pharmacologic inhibition of PAI-1 results in preservation of telomere length. Identification of a unique Amish kindred that harbors a loss-of-function mutation in SERPINE1 (c.699_700dupTA), which encodes PAI-1, provides a novel opportunity to assess the effects of lifelong PAI-1 deficiency on leukocyte telomere length (LTL) in humans. Methods: We conducted an observational study in the Old Order Amish, a founder population who originally settled in Berne, Indiana characterized by a homogeneous diet and lifestyle, and included participants aged 18 years and older. All study participants were genotyped for the c.699_700dupTA frameshift mutation in SERPINE1. For the primary analysis, we excluded participants who were homozygous for the null SERPINE1 mutation (n=7) due to their young age (18-34 years old) and small sample size. Relative LTL was quantified from peripheral blood using Southern blot of the terminal restriction fragments. We tested the association of SERPINE1 mutation status with LTL, after adjustment for age, sex, and relatedness in SOLAR. Results: A total of 170 participants were enrolled with mean age 46±19 years. Forty-three participants were identified as carriers of the null SERPINE1 mutation with an overall minor (null) allele frequency of 16% in the study population. SERPINE1 carriers had a significantly greater LTL compared with noncarriers, after adjustment for age, sex, and family structure (p=0.039; FIGURE). Every 1-year increase in age of study participant was associated with a 30 base pair decrease in LTL (p<0.0001). Conclusions: Heterozygosity for the null SERPINE1 gene, encoding a senescence-associated protein, PAI-1, is associated with longer LTL in a rare loss-of-function cohort. In addition, LTL is strongly and inversely correlated with chronologic age and supports the hypothesis that PAI-1 may contribute to cellular and organismal aging as reflected by LTL. Figure Mean telomere restriction fragments (kilobase pairs) as a function of age and genotype Figure. Mean telomere restriction fragments (kilobase pairs) as a function of age and genotype Disclosures Shapiro: CSL Behring: Other: Clinical research protocols; Kedrion Biopharma: Consultancy; Daiichi Sankyo: Other: Clinical research protocols; OPKO: Other: Clinical research protocols; National Hemophilia Foundation: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Other: Clinical research protocols; Novo Nordisk Hemophilia Foundation: Membership on an entity's Board of Directors or advisory committees; Baxter/Baxalta/Shire: Membership on an entity's Board of Directors or advisory committees, Other: Clinical research protocols; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Other: Clinical research protocols; Biogen: Membership on an entity's Board of Directors or advisory committees, Other: Clinical research protocols; Genentech: Membership on an entity's Board of Directors or advisory committees; American Thrombosis and Hemostasis Network: Other: Medical Director; ProMetic Life Sciences: Consultancy; Bayer healthcare Pharmaceuticals: Other: International network on pediatric hemophilia; Novartis: Other: Clinical research protocols; Selexys: Other: Clinical research protocols; Octopharma: Other: Clinical research protocols.


2000 ◽  
Vol 119 (3) ◽  
pp. 89-99 ◽  
Author(s):  
Ulrike Friedrich ◽  
Ernst-Ulrich Griese ◽  
Matthias Schwab ◽  
Peter Fritz ◽  
Klaus-Peter Thon ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Laila Bendix ◽  
Mikael Thinggaard ◽  
Masayuki Kimura ◽  
Abraham Aviv ◽  
Kaare Christensen ◽  
...  

Introduction. Fatigue is often present in older adults with no identified underlying cause. The accruing burden of oxidative stress and inflammation might be underlying factors of fatigue. We therefore hypothesized that leukocyte telomere length (LTL) is relatively short in older adults who experience fatigue.Materials and Methods. We assessed 439 older nondisabled Danish twins. LTL was measured using Southern blots of terminal restriction fragments. Fatigue was measured by the Mob-T Scale based on questions on whether the respondents felt fatigued after performing six mobility items.Results. LTL was significantly associated with fatigue (P=0.023), showing an increase of 0.038 kb/fatigue score unit. Aging-related diseases and mental health did not explain the association, while lifestyle factors slightly attenuated the estimates.Conclusion. Our results support an association between LTL and fatigue. Further studies are required to confirm this finding and the link of LTL with oxidative stress/inflammation over the life course.


2004 ◽  
Vol 24 (10) ◽  
pp. 4571-4580 ◽  
Author(s):  
Susanne Steinert ◽  
Jerry W. Shay ◽  
Woodring E. Wright

ABSTRACT There is a discrepancy in telomere length as measured by signal intensity of telomere restriction fragments on gels and fluorescence in situ hybridization analysis. This difference has been ascribed to the X-region, a segment of subtelomeric DNA that is resistant to being cut by restriction enzymes. To explore the nature of this region, we analyzed the digestibility of an artificial seeded telomere in HeLa cells as well as the Xp/Yp autosomal telomere in human BJ fibroblasts. We found that there is a substantial fraction of subtelomeric DNA containing restriction sites that is not digested with enzymes such as EcoRI, NlaIII, and SphI. Comparison of methylation-sensitive and -resistant enzymes excluded the possibility of the X-region being maintained by DNA methylation. We show that the X-region represents a variable domain whose size changes with telomere length, and neither non-TTAGGG sequences nor cytidine methylation can adequately explain the size of the X-region.


1981 ◽  
Vol 45 (02) ◽  
pp. 110-115 ◽  
Author(s):  
György Csákó ◽  
Eva A Suba

SummaryPlatelet aggregations were studied by a turbidimetric method in citrated human platelet-rich plasmas (PRP) in vitro. Human Clq inhibited the aggregations caused by collagens derived from different tissues and species. Clq was needed by weight in comparable quantities to collagen for neutralizing the aggregating effect. The dependence of the inhibitory reaction on the preincubation of platelets with Clq and the differences in the occurrence of aggregating substances in supernatants of PRP triggered with collagen in the presence or absence of Clq, confirmed that Clq exerts its effect by preventing fixation of collagen to platelets. In addition, the high specificity of the inhibitory action of Clq for collagen-induced platelet aggregation was demonstrated by results obtained for testing a variety of aggregating agents in combination with Clq and/or collagen.Since normal concentrations of Clq in the blood are in the range of inhibitory doses of Clq for collagen-induced platelet aggregations in vitro and upon activation of complement Clq is known to dissociate from Cl, it is proposed that Clq may participate in a highly specific manner in regulating platelet reactivity to collagen in vivo.


2014 ◽  
Vol 514 ◽  
pp. 217-229 ◽  
Author(s):  
HY Wang ◽  
LW Botsford ◽  
JW White ◽  
MJ Fogarty ◽  
F Juanes ◽  
...  

2013 ◽  
Author(s):  
Anna Aulinas ◽  
Ramirez Maria Jose ◽  
Barahona Maria Jose ◽  
Eugenia Mato ◽  
Olga Bell ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document