Cross-species Association Between Telomere Length and Glucocorticoid Exposure

2021 ◽  
Author(s):  
Richard S Lee ◽  
Peter P Zandi ◽  
Alicia Santos ◽  
Anna Aulinas ◽  
Jenny L Carey ◽  
...  
Keyword(s):  
Telomere Length ◽  
Genomic Dna ◽  
Chronic Exposure ◽  
Disease Onset ◽  
Neuronal Cell ◽  
Accelerated Aging ◽  
Stress Exposure ◽  
Healthy Human ◽  
Species Association ◽  
Medical Disorders

Abstract Context Chronic exposure to glucocorticoids (GCs) or stress increases the risk of medical disorders, including cardiovascular and neuropsychiatric disorders. GCs contribute to an accelerated aging, while the link between chronic GCs exposure and disease onset is well established, the underpinning mechanisms are not clear. Objective we explored the potential nexus between GCs or stress exposure and telomere length. Design, Setting, and Participants rats exposed to three weeks of chronic stress; an iatrogenic mouse model of Cushing’s syndrome (CS); a mouse neuronal cell line; 33 patients with CS and 75 healthy human people were studied. Results 1.Telomere length is associated with exposure to stress in rats: 54.5% (P=0.036) reduction in telomere length in the stressed animals. Genomic DNA extracted from the dentate gyrus of stressed and unstressed rats showed 43.2% reduction in telomere length (P=0.006). 2. Mice were exposed to corticosterone (CORT), this treatment produced a 61.4% reduction in telomere length in the blood gDNA (P=5.75x 10-5). 3. We observed a 40.8% reduction in the telomere length in patients with active CS compared to healthy controls (P=0.006). There was a 17.8% reduction in telomere length in cured CS patients, no different from controls (P=0.08). For both cured and active CS, telomere length correlated significantly with the duration of hypercortisolism (R2=0.22, P=0.007). 4. There was a 27.6% reduction in telomere length between low vs. high tertiles in bedtime cortisol levels (P=0.019). Conclusions Our findings demonstrate that exposure to stress and/or glucocorticoids is associated with shortened telomeres, and that shortening may be partially reversible.

scholarly journals Chromosome Instability, Aging and Brain Diseases

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1256
Author(s):  
Ivan Y. Iourov ◽  
Yuri B. Yurov ◽  
Svetlana G. Vorsanova ◽  
Sergei I. Kutsev
Keyword(s):  
Brain Aging ◽  
Chromosome Instability ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Accelerated Aging ◽  
Brain Diseases ◽  
Aging Brain ◽  
Ontogenetic Changes ◽  
Health And Disease

Chromosome instability (CIN) has been repeatedly associated with aging and progeroid phenotypes. Moreover, brain-specific CIN seems to be an important element of pathogenic cascades leading to neurodegeneration in late adulthood. Alternatively, CIN and aneuploidy (chromosomal loss/gain) syndromes exhibit accelerated aging phenotypes. Molecularly, cellular senescence, which seems to be mediated by CIN and aneuploidy, is likely to contribute to brain aging in health and disease. However, there is no consensus about the occurrence of CIN in the aging brain. As a result, the role of CIN/somatic aneuploidy in normal and pathological brain aging is a matter of debate. Still, taking into account the effects of CIN on cellular homeostasis, the possibility of involvement in brain aging is highly likely. More importantly, the CIN contribution to neuronal cell death may be responsible for neurodegeneration and the aging-related deterioration of the brain. The loss of CIN-affected neurons probably underlies the contradiction between reports addressing ontogenetic changes of karyotypes within the aged brain. In future studies, the combination of single-cell visualization and whole-genome techniques with systems biology methods would certainly define the intrinsic role of CIN in the aging of the normal and diseased brain.

scholarly journals Telomere Shortening and Accelerated Aging in US Military Veterans

2021 ◽  
Vol 18 (4) ◽  
pp. 1743
Author(s):  
Jeffrey T. Howard ◽  
Jud C. Janak ◽  
Alexis R. Santos-Lozada ◽  
Sarah McEvilla ◽  
Stephanie D. Ansley ◽  
...  
Keyword(s):  
Telomere Length ◽  
Military Service ◽  
Accelerated Aging ◽  
Cellular Aging ◽  
Veterans Health ◽  
Cvd Risk ◽  
Base Pairs ◽  
Telomere Shortening ◽  
Race Ethnicity ◽  
Service Data

A growing body of literature on military personnel and veterans’ health suggests that prior military service may be associated with exposures that increase the risk of cardiovascular disease (CVD), which may differ by race/ethnicity. This study examined the hypothesis that differential telomere shortening, a measure of cellular aging, by race/ethnicity may explain prior findings of differential CVD risk in racial/ethnic groups with military service. Data from the first two continuous waves of the National Health and Nutrition Examination Survey (NHANES), administered from 1999–2002 were analyzed. Mean telomere length in base pairs was analyzed with multivariable adjusted linear regression with complex sample design, stratified by sex. The unadjusted mean telomere length was 225.8 base shorter for individuals with prior military service. The mean telomere length for men was 47.2 (95% CI: −92.9, −1.5; p < 0.05) base pairs shorter for men with military service after adjustment for demographic, socioeconomic, and behavioral variables, but did not differ significantly in women with and without prior military service. The interaction between military service and race/ethnicity was not significant for men or women. The results suggest that military service may contribute to accelerated aging as a result of health damaging exposures, such as combat, injury, and environmental contaminants, though other unmeasured confounders could also potentially explain the results.

scholarly journals Molecular Mechanisms Underlying Synaptic and Axon Degeneration in Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Nolwazi Z. Gcwensa ◽  
Drèson L. Russell ◽  
Rita M. Cowell ◽  
Laura A. Volpicelli-Daley
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Disease Onset ◽  
Neuronal Cell ◽  
Rem Sleep Behavior Disorder ◽  
Dopamine Neurons ◽  
Neuronal Cell Body ◽  
Substantia Nigra Pars Compacta ◽  
Cognitive Changes

Parkinson’s disease (PD) is a progressive neurodegenerative disease that impairs movement as well as causing multiple other symptoms such as autonomic dysfunction, rapid eye movement (REM) sleep behavior disorder, hyposmia, and cognitive changes. Loss of dopamine neurons in the substantia nigra pars compacta (SNc) and loss of dopamine terminals in the striatum contribute to characteristic motor features. Although therapies ease the symptoms of PD, there are no treatments to slow its progression. Accumulating evidence suggests that synaptic impairments and axonal degeneration precede neuronal cell body loss. Early synaptic changes may be a target to prevent disease onset and slow progression. Imaging of PD patients with radioligands, post-mortem pathologic studies in sporadic PD patients, and animal models of PD demonstrate abnormalities in presynaptic terminals as well as postsynaptic dendritic spines. Dopaminergic and excitatory synapses are substantially reduced in PD, and whether other neuronal subtypes show synaptic defects remains relatively unexplored. Genetic studies implicate several genes that play a role at the synapse, providing additional support for synaptic dysfunction in PD. In this review article we: (1) provide evidence for synaptic defects occurring in PD before neuron death; (2) describe the main genes implicated in PD that could contribute to synapse dysfunction; and (3) show correlations between the expression of Snca mRNA and mouse homologs of PD GWAS genes demonstrating selective enrichment of Snca and synaptic genes in dopaminergic, excitatory and cholinergic neurons. Altogether, these findings highlight the need for novel therapeutics targeting the synapse and suggest that future studies should explore the roles for PD-implicated genes across multiple neuron types and circuits.

scholarly journals Influence of Different Types of Resin Luting Agents on Color Stability of Ceramic Laminate Veneers Subjected to Accelerated Artificial Aging

2016 ◽  
Vol 27 (1) ◽  
pp. 95-100 ◽  
Author(s):  
Francisca Daniele Jardilino Silami ◽  
Rafaella Tonani ◽  
Carla Cecilia Alandia-Román ◽  
Fernanda de Carvalho Panzeri Pires-de-Souza
Keyword(s):  
Accelerated Aging ◽  
Color Stability ◽  
Resin Cements ◽  
Healthy Human ◽  
Color Changes ◽  
Luting Agents ◽  
Occlusal Surfaces ◽  
Initial Color ◽  
Laminate Veneers ◽  
Adhesive Cement

Abstract The aim of this study was to evaluate the influence of accelerated aging (AAA) on the color stability of resin cements for bonding ceramic laminate veneers of different thicknesses. The occlusal surfaces of 80 healthy human molars were flattened. Ceramic laminate veneers (IPS e-max Ceram) of two thicknesses (0.5 and 1.0 mm) were bonded with three types of luting agents: light-cured, conventional dual and self-adhesive dual cement. Teeth without restorations and cement samples (0.5 mm) were used as control. After initial color evaluations, the samples were subjected to AAA for 580 h. After this, new color readouts were made, and the color stability (ΔE) and luminosity (ΔL) data were analyzed. The greatest color changes (p<0.05) occurred when 0.5 mm veneers were fixed with light-cured cement and the lowest when 1.0 mm veneers were fixed with conventional dual cement. There was no influence of the restoration thickness when the self-adhesive dual cement was used. When veneers were compared with the control groups, it was verified that the cement samples presented the greatest alterations (p<0.05) in comparison with both substrates and restored teeth. Therefore, it was concluded that the thickness of the restoration influences color and luminosity changes for conventional dual and light-cured cements. The changes in self-adhesive cement do not depend on restoration thickness.

scholarly journals Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

2011 ◽  
Vol 108 (33) ◽  
pp. E513-E518 ◽  
Author(s):  
S. Entringer ◽  
E. S. Epel ◽  
R. Kumsta ◽  
J. Lin ◽  
D. H. Hellhammer ◽  
...  
Keyword(s):  
Telomere Length ◽  
Young Adulthood ◽  
Stress Exposure ◽  
Intrauterine Life

Telomerase Activity and Telomere Length of CD4+CD25+ Regulatory T-Cells under Conditions of In Vitro and In Vivo Expansion.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3857-3857
Author(s):  
Dominik G.F. Wolf ◽  
Anna M. Wolf ◽  
Christian Koppelstaetter ◽  
Holger F. Rumpold ◽  
Gert Mayer ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Telomere Length ◽  
Cancer Patients ◽  
Telomerase Activity ◽  
Telomere Maintenance ◽  
Healthy Human ◽  
Telomere Shortening

Abstract The expandability of CD4+CD25+ regulatory T-cells (Treg) has been shown in vitro and in vivo. Activation of telomerase activity is a prerequisite for clonal expansion and telomere maintenance in T-cells. There is currently no data available on the expression and function of telomerase in proliferating Treg. Analyses of telomere length by flow-FISH, real-time PCR and Southern blotting revealed that Treg isolated from healthy human volunteers have significantly shortened telomeres when compared to CD4+CD25− T-cells. However, telomere length is not further shortened in Treg isolated from the peripheral blood of cancer patients, despite the observation that the regulatory T-cell pool of these patients was significantly enlarged. To gain further insight into maintenance of telomere length of Treg, we induced in vitro proliferation of Treg by stimulation with anti-CD3 and IL-2. This led to a rapid increase of telomerase activity, as determined by PCR-ELISA. However, when we focused on the proliferating fraction of Treg using a sorting strategy based on the dilution of CFSE, we could show a significant telomere shortening in Treg with high proliferative and immmuno-suppressive capacity. Of note, proliferating CFSElow Treg are characterized by high telomerase activity, which however seems to be insufficient to avoid further telomere shortening under conditions of strong in vitro stimulation. In contrast, under conditions of in vivo expansion of Treg in cancer patients, the induction of telomerase activity is likely to compensate for further telomere erosion. These data might be of importance when considering the application of in vitro expanded Treg for the treatment of GvHD or autoimmune diseases, as telomere shortening might be associated with genomic instability.

Increased Telomere Length Is a Negative a Predicting Factor for IST in Children with Severe Aplastic Anemia?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4381-4381
Author(s):  
Katarzyna Pawelec ◽  
Marek Janiak ◽  
Michał Matysiak ◽  
Pawel Krzysztof Wlodarski
Keyword(s):  
Aplastic Anemia ◽  
Telomere Length ◽  
Peripheral Blood ◽  
Genomic Dna ◽  
Antithymocyte Globulin ◽  
Single Copy ◽  
Single Copy Gene ◽  
Blood Samples ◽  
Copy Gene ◽  
Predicting Factor

Abstract Abstract 4381 Shortening of telomeres is observed in 1/3 of peripheral blond samples, collected from patients with severe aplastic anemia (SAA). Probably, this phenomenon is associated with poor response to immunosuppressive therapy –IST (antithymocyte globulin -ATG and cyklosporin-CSA). The aim of this study was to assess the length of telomeres in peripheral blood of children with SAA treated with antithymocyte globulin (ATG) and cyklosporin (CSA) Materials and Methods: Peripheral blood samples were collected from 13 children with confirmed SAA. Patients (9 girls and 4 boys) aged 7–19 yrs have all received rabbit ATG in a dose of 3.75 mg/kg/day for 5 days and CSA in a dose of 5mg/kg/day for 12–14 months). Remission was assessed on 180th and 360th day of treatment. Control peripheral blood samples were obtained from 12 healthy children (3 girls and 9 boys, aged 3–17 yrs), 12 healthy adultand from 4 SAA children parents. Informed consent was obtained from all adult donors and from parents of participating children. DNA extraction and qPCR Genomic DNA was extracted from whole blood using AxyPrep Blood Genomic DNA Miniprep Kit (Axygene). Telomere length was determined using the quantitive PCR (qPCR) method described by Elisa Pavesi et al (1). Briefly, two qPCR reactions were run for each DNA sample: amplification of telomere product and amplification of a single copy gene (SEP15). Each qPCR reaction contained: Power SYBR1 Green PCR Master Mix (Applied Biosystems), template DNA and primers (270nM Tel1 and 900nM Tel2 or 500nM of each SEP15 primers). Telomere/single copy gene (T/S) ratios for samples were calculated using Human reference DNA (Applied Biosystems) standard curve. Reactions were preformed in Real Time PCR CFX96 system (Biorad). Statistica software version 9.1 (StatSoft) was used for statistical analysis Results: Among 13 SAA patients telomere shortening was found in 9 children while 4 patients had significantly elongated telomeres. All of the latter ones responded poorly to IST treatment: 3 of them did not respond (NR) to IST (neither on day 180 nor on 360) and one patient had a partial remission (PR). 2 patients in the NR group were randomized to unrelated bone marrow transplantation and one had another course of IST (no unrelated donor), after which he reached a PR. All patients with elongated telomeres had normal serum adriostendion level. Telomere elongation was also found in parents compared to the control group of adults (n=12, age range 31–57). Among 9 patients with shortened telomeres, 4 achieved complete remission (CR), 1 - PR and 4 did not respond (NR) to treatment on check times points. Conclusions: Our observations indicate that SAA patients with shortened telomeres respond to immunosuppressive therapy better then those with elongated telomeres. Telomere length may be considered therefore as a predicting factor in this patients. Studies on a larger group of patients should be performed to confirm our observations. Short telomere definition –samples, which T/S value is less than the first Quartile of controls. Long telomere - samples, which T/S value is in III quartile of controls. Very long telomere - samples, which T/S value is higher than the IV Quartile of controls. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Adiposity and insulin resistance correlate with telomere length in middle-aged Arabs: the influence of circulating adiponectin

2010 ◽  
Vol 163 (4) ◽  
pp. 601-607 ◽  
Author(s):  
Omar S Al-Attas ◽  
Nasser M Al-Daghri ◽  
Majed S Alokail ◽  
Assim Alfadda ◽  
Ahmed Bamakhramah ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Telomere Length ◽  
Serum Insulin ◽  
Accelerated Aging ◽  
Model Assessment ◽  
Protective Effects ◽  
Ang Ii ◽  
Middle Aged

ObjectiveStudies in obesity have implicated adipocytokines in the development of insulin resistance, which in turn may lead to accelerated aging. In this study, we determined associations of chromosomal telomere length (TL) to markers of obesity and insulin resistance in middle-aged adult male and female Arabs with and without diabetes mellitus type 2 (DMT2).Design and methodsOne hundred and ninety-three non-diabetic and DMT2 subjects without complications (97 males and 96 females) participated in this cross-sectional study. Clinical data, as well as fasting blood samples, were collected. Serum glucose and lipid profile were determined using routine laboratory methods. Serum insulin, leptin, adiponectin, resistin, tumor necrosis factor-α, and PAI-1 were quantified using customized multiplex assay kits. High sensitive C-reactive protein (hsCRP) and angiotensin II (ANG II) were measured using ELISAs. Circulating leukocyte TL was examined by quantitative real-time PCR.ResultsCirculating chromosomal leukocyte TL had significant inverse associations with body mass index (BMI), systolic blood pressure, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein (LDL)- and total cholesterol, ANG II and hsCRP levels. Adiponectin, BMI, systolic blood pressure, and LDL cholesterol predicted 47% of the variance in TL (P<0.0001). HOMA-IR was the most significant predictor for TL in males, explaining 35% of the variance (P=0.01). In females, adiponectin accounted for 28% of the variance in TL (P=0.01).ConclusionObesity and insulin resistance are associated with chromosomal TL among adult Arabs. Evidence of causal relations needs further investigation. The positive association of adiponectin to TL has clinical implications as to the possible protective effects of this hormone from accelerated aging.

Decreased leukocyte telomere length in male patients with chronic bipolar disorder: lack of effect of long-term lithium-treatment

2021 ◽  
pp. 1-25
Author(s):  
Ewa Ferensztajn-Rochowiak ◽  
Ewa Kurczewska ◽  
Błażej Rubiś ◽  
Michalina Lulkiewicz ◽  
Hanna Hołysz ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Telomere Length ◽  
Lithium Treatment ◽  
Quantitative Polymerase Chain Reaction ◽  
Accelerated Aging ◽  
Control Group ◽  
Duration Of Treatment ◽  
Control Male ◽  
Bipolar Patients

Abstract Objectives: Bipolar disorder (BD) may be connected with accelerated aging, the marker of this can be shorter telomere length (TL). Some data suggest that lithium may exert a protective effect against telomere shortening. The study aimed to compare the telomere length between patients with bipolar disorder and control subjects. The effect of long-term lithium treatment was also assessed. Methods: The study group comprised 41 patients with BD, including 29 patients treated longitudinally with lithium (mean 16.5 years) and 20 healthy people. Telomere length was assessed by the quantitative polymerase chain reaction (qPCR). Results: In the control group, the TL was significantly longer in males than in females. Male bipolar patients had significantly shorter TL compared with the control male group. In bipolar patients, there was no correlation between TL and duration of treatment. The TL was negatively correlated with age in male bipolar patients. Conclusion: The study did not confirm the lithium effect on TL in bipolar patients. TL showed gender differences, being shorter in BD males, compared to control males, and longer in healthy males, compared to control females.

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