scholarly journals Impact of Yoga and Meditation on Cellular Aging in Apparently Healthy Individuals: A Prospective, Open-Label Single-Arm Exploratory Study

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Madhuri Tolahunase ◽  
Rajesh Sagar ◽  
Rima Dada
Keyword(s):  
Telomere Length ◽  
Exploratory Study ◽  
Telomerase Activity ◽  
Cellular Aging ◽  
Sirtuin 1 ◽  
Healthy Individuals ◽  
Open Label ◽  
The Mean ◽  
The Impact ◽  
Apparently Healthy

This study was designed to explore the impact of Yoga and Meditation based lifestyle intervention (YMLI) on cellular aging in apparently healthy individuals. During this 12-week prospective, open-label, single arm exploratory study, 96 apparently healthy individuals were enrolled to receive YMLI. The primary endpoints were assessment of the change in levels of cardinal biomarkers of cellular aging in blood from baseline to week 12, which included DNA damage marker 8-hydroxy-2′-deoxyguanosine (8-OH2dG), oxidative stress markers reactive oxygen species (ROS), and total antioxidant capacity (TAC), and telomere attrition markers telomere length and telomerase activity. The secondary endpoints were assessment of metabotrophic blood biomarkers associated with cellular aging, which included cortisol, β-endorphin, IL-6, BDNF, and sirtuin-1. After 12 weeks of YMLI, there were significant improvements in both the cardinal biomarkers of cellular aging and the metabotrophic biomarkers influencing cellular aging compared to baseline values. The mean levels of 8-OH2dG, ROS, cortisol, and IL-6 were significantly lower and mean levels of TAC, telomerase activity, β-endorphin, BDNF, and sirtuin-1 were significantly increased (all values p<0.05) post-YMLI. The mean level of telomere length was increased but the finding was not significant (p=0.069). YMLI significantly reduced the rate of cellular aging in apparently healthy population.

scholarly journals Telomere biology and metabolic disorders: the role of insulin resistance and type 2 diabetes

2020 ◽  
Vol 66 (4) ◽  
pp. 35-44
Author(s):  
Ekaterina N. Dudinskaya ◽  
Olga N. Tkacheva ◽  
Natalia V. Brailova ◽  
Irina D. Strazhesko ◽  
Marina V. Shestakova
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Carbohydrate Metabolism ◽  
Telomere Length ◽  
Telomerase Activity ◽  
Cellular Aging ◽  
The Mean ◽  
Telomere Biology

BACKGROUND: Insulin resistance accelerates the aging process, but its speed depends on the individual characteristics of the metabolism. One of the reasons for the different aging rates in individuals with insulin resistance is the initially different “genetic protection” of cells, which many scientists associate with replicative cellular aging.AIMS: to study the relationship between the state of carbohydrate metabolism and markers of replicative cell aging in individuals with different sensitivity to insulin.MATERIALS AND METHODS: The observation study included 305 patients. The parameters of glucose metabolism and telomere biology were studied.RESULTS: The mean age of the patients was 51.5±13.3 years. Patients were divided into three groups depending on presence of insulin resistance: healthy, with insulin resistance and with type 2 diabetes. The mean age of healthy patients was 48.82±13.87 years, in insulin resistance group — 53.04±12.8, in 2 diabetes mellitus — 58.4±7.90. The median telomere length was 9.76. The median telomerase activity was 0.48. Both telomere length and telomerase activity progressively decrease as insulin resistance increases. In patients with diabetes, short telomere lengths and low telomerase activity predominated. The insulin resistance index has the greatest impact on the risk of detecting “short” telomeres. In patients with insulin resistance, an increase in glycated hemoglobin increases the likelihood of detecting short telomeres by 2.4 times, and in diabetes mellitus by 4.26 times, an increase in fasting plasma glucose by 90%, and an increase in HOMA-IR by 35%. An increase in insulin resistance increases the risk of detecting «low» telomerase activity by 53% and the risk of detecting «very low» telomerase activity by 92%. A decrease in synsulin resistance increases the chance of increasing telomerase activity to «very high» by 51%.CONCLUSION: Shorter telomeres are associated with more pronounced disorders of carbohydrate metabolism and a higher degree of insulin resistance. Further studies of metabolic status are necessary to personalize their lifestyle and treatment goals.

Accelerated telomere shortening in glycosylphosphatidylinositol (GPI)–negative compared with GPI-positive granulocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) detected by proaerolysin flow-FISH

Blood ◽  
2005 ◽  
Vol 106 (2) ◽  
pp. 531-533 ◽  
Author(s):  
Fabian Beier ◽  
Stefan Balabanov ◽  
Tom Buckley ◽  
Klaus Dietz ◽  
Ulrike Hartmann ◽  
...  
Keyword(s):  
Telomere Length ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Bone Marrow Failure ◽  
Disease Stage ◽  
Healthy Individuals ◽  
Hematopoietic Stem ◽  
Replicative Stress ◽  
Selective Growth Advantage ◽  
Bone Marrow Failure Syndromes ◽  
The Impact

Abstract Telomere length has been linked to disease stage and degree of (pan-)cytopenia in patients with bone marrow failure syndromes. The aim of the current study was to analyze the impact of replicative stress on telomere length in residual glycosylphosphatidylinositol-positive (GPI+) versus GPI– hematopoiesis in patients with paroxysmal nocturnal hemoglobinuria (PNH). Peripheral blood granulocytes from 16 patients and 22 healthy individuals were analyzed. For this purpose, we developed proaerolysin flow-FISH, a novel methodology that combines proaerolysin staining (for GPI expression) with flow-FISH (for telomere length measurement). We found significantly shortened telomeres in GPI– granulocytes (mean ± SE: 6.26 ± 0.27 telomere fluorescence units [TFU]), both compared with their GPI+ counterparts (6.88 ± 0.38 TFU; P = .03) as well as with age-matched healthy individuals (7.73 ± 0.23 TFU; P &lt; .001). Our findings are in support of a selective growth advantage model of PNH assuming that damage to the GPI+ hematopoietic stem-cell (HSC) compartment leads to compensatory hyperproliferation of residual GPI–HSCs.

161 MODULATION OF TELOMERASE ACTIVITY IN BOVINE EMBRYOS USING CYTOPLASMATIC PLASMID INJECTION

2010 ◽  
Vol 22 (1) ◽  
pp. 239
Author(s):  
W. Garrels ◽  
W. Kues ◽  
U. Baulain ◽  
H. Niemann
Keyword(s):  
Telomere Length ◽  
Telomerase Activity ◽  
Control Group ◽  
Activity Measurement ◽  
Bovine Embryos ◽  
Gfp Fluorescence ◽  
Plasmid Injection ◽  
Significant Extension ◽  
Human Telomerase ◽  
The Impact

Telomeres are repetitive, noncoding sequences at the ends of linear chromosomes that shorten with each cell division. They play an important role in aging and affect the regenerative capacity of cells. The holoenzyme telomerase rebuilds telomeres and is composed of 2 components, i.e. the catalytic protein component telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC). In mammals, telomerase is active during embryogenesis, in germ cells and a subset of stem and progenitor cells. In the present study, we set out to express the TERC component alone and then in combination with TERT, the human telomerase complex, in bovine embryos. The human telomerase components are highly homologous to bovine telomerase genes. Here, 3 different expression constructs encoding hTERC, hTERT, and a green fluorescent protein (GFP) reporter were co-injected into bovine zygotes cytoplasm, and three groups of 528, 1865, and 110 zygotes were constituted; hTERC/GFP (Group 1), hTERT/hTERC/GFP (Group 2), and GFP alone (Group 3), respectively. GFP fluorescence was used to identify successfully injected embryos. This method has recently been established in our laboratory. Injected and control embryos were cultured for 7 days to the blastocyst stage in vitro and the impact on early embryonic development and the physiological consequences of an ectopic overexpression of telomerase in early bovine embryos were assayed. We obtained 45 blastocysts with green fluorescence in the first, 192 in the second, and 28 in the third group. Embryos with GFP fluorescence were frozen for subsequent PCR analysis and telomerase activity measurement. Some blastocyts were analyzed using quantitative fluoresence in situ hybridization to monitor telomere length. Control groups were analyzed for the endogenous levels of TERC and TERT. Results indicate that endogenous TERC and TERT are up-regulated in morulae and blastocyts. In this study, we show that human TERC and TERT can be expressed in blastocysts by cytoplasmic plasmid injection in bovine zygotes. Statistical analyses were performed using the JMP 7.0.1 for Windows software (SAS Institute Inc., Cary, NC, USA). The Tukey-Kramer test was applied to compare the group means. The expression of hTERC alone resulted in a significant extension of telomere length of 280 telomere fluorescence units. Expression of both components also resulted in a significant extension of telomere length. In conclusion, TERC component alone is sufficient to elongate telomere length. The activity measurement showed that telomerase activity in the hTERT and hTERC injected group is 1.77 times higher than in the control group. Findings from this study will allow a comprehensive analysis of the functions of TERT and TERC in early embryogenesis. The ectopic expression of telomerase components in bovine embryos could pave new avenues for generating stem cells and for the development of novel regenerative therapies. Funded by DFG.

Deferasirox (ICL670; Exjade®) Reduces Serum Ferritin (SF) and Labile Plasma Iron (LPI) in Patients with Myelodysplastic Syndromes (MDS).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1470-1470 ◽  
Author(s):  
Alan F. List ◽  
M.R. Baer ◽  
D. Steensma ◽  
A. Raza ◽  
J. Esposito ◽  
...  
Keyword(s):  
Iron Reduction ◽  
Iron Status ◽  
Iron Chelation ◽  
Risk Groups ◽  
Morbidity And Mortality ◽  
Endocrine Function ◽  
Open Label ◽  
Nccn Guidelines ◽  
The Mean ◽  
The Impact

Abstract INTRODUCTION: The majority of patients (pts) with MDS become red blood cell (RBC) transfusion dependent with escalating risk for transfusional hemosiderosis and its adverse effect on morbidity and mortality. The US03 trial is designed to evaluate long-term efficacy and safety of the oral iron chelator, deferasirox (DFX), in pts with lower risk MDS. In this ongoing study 53 pts have completed 12 months’ (mos) treatment. METHODS: US03 is a Phase II, open-label, 3-year trial in pts with Low- or Int-1 IPSS risk MDS and transfusional iron overload (SF ≥1000 μg/L and &gt;20 units RBC transfusions [tx]), with serum creatinine (SCr) ≤2-fold the upper limit of normal (ULN). Initial DFX dose was 20 mg/kg/day and could be increased to 40 mg/kg/day based on tolerability and response. SF was monitored monthly; LPI, the reactive species of non-transferrin-bound iron, was assessed quarterly. BASELINE FEATURES: 176 pts were enrolled at 45 centers. Mean age was 70 years (range, 21−90), including 102 men, 71 women; and IPSS risk groups of Low 46 pts (27%), Int-1 123 (71%), other 4 (2%). Mean baseline iron status: SF 3398 μg/L (range, 863−36,280); LPI 0.4 μmol/L (0.0−3.6); mean lifetime txs prior to study, 63; years of prior tx 3.5 (0−34). MDS therapy at study entry included chemotherapy, 22 pts; growth factors, 46. Estimated creatinine clearance: normal (&gt;80 mL/min), 77 pts; mild (51−80 mL/min), 68; moderate, (30–50 mL/min) 25; severe (&lt;30 mL/min) 2. Over 12 mos the mean dose was 21 mg/kg/day, and the mean tx rate was 4.1 units/mo. Forty percent of pts had elevated LPI at baseline (≥0.5 μmol/L). RESULTS: Mean SF±SD (μg/L) values: baseline 3398±3088; 3 mos 3065±1743; 6 mos 2775±1355; 9 mos 2759±1562; 12 mos 2603±1336. Sustained suppression of mean LPI to the normal range was achieved after 3 mos of treatment. (Figure shows changes in SF and LPI). Hematologic improvement by IWG criteria: 5 pts (6%); erythroid response: 3 (major 1; minor 2); platelet 2 (major); neutrophil 1 (major). SAFETY: Of 165 pts, only 10 (6%) discontinued secondary to suspected adverse events (AEs), and 7 (4%) serious AEs. There were 11 deaths (7%), all unrelated to DFX. Of 140 pts with normal baseline SCr, 35 (25%) increased &gt;ULN (2.2 mg/dL max SCr). SCr increased &gt;33% above baseline in 11 pts (8%) abnormal at baseline. New onset of thrombocytopenia and neutropenia were 52/165 (32%) and 22/165 (13%), respectively. CONCLUSIONS: DFX therapy decreased mean SF over 1 year in this heavily iron-replete MDS population. Trough LPI normalized in 100% of pts over 12 mos, indicating 24-hour sustained suppression. DFX had a manageable safety profile in this population; new cytopenias were consistent with hematologic progression of MDS. Recent reviews show a 30% increase in hazard ratio for every 500 ng/mL increase in SF &gt;1000 ng/mL; NCCN guidelines recommend consideration of iron chelation in iron-overloaded MDS pts. Ongoing assessments evaluating cardiac, hepatic and endocrine function will evaluate the impact of iron reduction on morbidity and mortality in MDS. Figure Figure

scholarly journals The role of telomerase in the etiology of primary spontaneous pneumothorax

2021 ◽  
Vol 29 (3) ◽  
pp. 377-383
Author(s):  
Mehmet Akif Tezcan ◽  
İbrahim Ethem Özsoy ◽  
Fatih Gürler ◽  
Çiğdem Karakükçü
Keyword(s):  
Spontaneous Pneumothorax ◽  
Telomerase Activity ◽  
Primary Spontaneous Pneumothorax ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Healthy Individuals ◽  
Genetic Studies ◽  
Thoracic Computed Tomography ◽  
The Mean

Background: This study aims to investigate the role of telomerase activity in the risk of primary spontaneous pneumothorax, which is most frequently encountered in the practice of thoracic surgery. Methods: A total of 61 patients (56 males, 5 females; median age: 29.4 years; range, 17 to 43 years) who underwent treatment for primary spontaneous pneumothorax and 19 age- and sex-matched healthy controls (10 males, 9 females; median age: 29.1 years; range, 23 to 43 years) were included in this prospective study between January 2018 - August 2018. Telomerase activity was evaluated with enzyme-linked immunosorbent assay. The correlation between telomerase activity and clinical and demographic parameters was examined. Results: The mean serum telomerase level was 3.4±0.6 ng/mL in the primary spontaneous pneumothorax group and 1.9±0.5 ng/mL in the control group, indicating significantly higher levels in the patient group (p<0.001). There was no significant association between the telomerase levels and presence of blebs and/or bullae on thoracic computed tomography, extent of pneumothorax, laterality (right, left, or bilateral), and pack years of cigarette smoking. Conclusion: Telomerase levels of patients with primary spontaneous pneumothorax are significantly higher than healthy individuals. Future genetic studies may ultimately clarify a potential relationship between primary spontaneous pneumothorax and short telomere syndrome.

scholarly journals Effect of Physical Exercise in Remodeling Telomere Length and Cancer Prevention in an Epigenetic Prospect – A Systematic Review

2021 ◽  
Vol 14 (02) ◽  
pp. 891-901
Author(s):  
Lavanya Prathap ◽  
Prathap Suganthirababu S ◽  
Praveen Kumar K ◽  
Preetha S
Keyword(s):  
Systematic Review ◽  
Physical Exercise ◽  
Cancer Prevention ◽  
Telomere Length ◽  
Telomerase Activity ◽  
Risk Of Bias ◽  
Epigenetic Mechanism ◽  
The Impact ◽  
Expression Status ◽  
P16 Expression

Background: Physical exercise has its impact at the molecular level and aids in healthy well-being of an individual. The current systematic review emphasis on the impact of physical exercise on the telomere length in cancer prevention through epigenetic mechanism. Evidences support the impact of physical exercise in alteration of telomere length through its influence in telomerase activity. The aim of the systematic review is to analyze the effect of physical exercise in remodeling the telomere length in cancer prevention in an epigenetic prospect. Material and Methods: We conducted a qualitative systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The systematic literature search covers articles ranging from the year 2010 to 2020. The Database used for literature searches are PubMed, Cochrane, Science Direct and Google scholar. The Medical Subject Headings (MeSH) used for search include ‘Cancer’ ‘exercise’ ‘Telomere length’ ‘telomerase expression’. The outcome variables include the telomere length, telomerase activity, telomere protein stabilizing gene expression status, Micro RNA expression status. Results: After exclusion of irrelevant articles 05 records are selected for final inclusion of the study and are analyzed using a Cochrane risk of bias assessment tool and SANRA tool found to be at low risk of bias and moderate quality respectively. The findings suggest chronic exercise is found to modulate the genetic and epigenetic equilibrium by either up regulation of p53 and p16 expression and stabilizing the telomerase activity within the limits or by increasing the telomerase activity and stabilizing the p53 and p16 expression within limits and impact telomere length, thus maintaining the genetic and epigenetic equilibrium. Conclusion: Based on the evidences collected it can be suggested that chronic moderate intensity aerobic exercise in a lifelong practice shows beneficial effects in a dose-response manner in cancer prevention in a novel way by modulating telomeres through epigenetic mechanism.

Short Telomeres Combined with Low Telomerase Activity Are Associated with a Longer Survival in Patients with Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4262-4262
Author(s):  
Veronique Saada ◽  
Pierre Tran Ba Loc ◽  
Camille Legeai ◽  
Marine Castaing ◽  
Jean-Henri Bourhis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Survival Analysis ◽  
Telomere Length ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Telomerase Activity ◽  
Htert Mrna ◽  
The Impact ◽  
Acute Myeloid

Abstract Telomeres - the terminal regions of human chromosomes, and enzyme telomerase - a ribonucloprotein that synthesizes telomeric DNA onto chromosomal ends, have been thoroughly investigated as potential markers for the prognosis of various cancers including leukemia. However, it is important to consider both parameters and only few studies have investigated the prognostic value of these two combined biomarkers in patients with acute myeloid leukemia (AML). Our work was designed to determine the impact of telomere length together with telomerase activity (TA) on survival in patients with AML. In this current retrospective study, TA (reflected by the quantitative expression of the catalytic subunit of telomerase i.e the hTERT mRNA/18s RNA ratio measured by Q-RT-PCR) and telomere length (determined by southern blot analysis of terminal restriction fragments) were assayed in the bone marrow of 40 patients diagnosed with AML between 1999 and 2003 at Institute Gustave Roussy’s division of Hematology. The patients’ characteristics are shown on table 1. All patients were treated according to standard AML-type chemotherapy protocols. The median of TA (hTERT mRNA/18s RNA ratio) was 0.0458. TA was not detectable in 4 patients. The median of telomere length was 7.6 Kb (range: 3.5–11.2 Kb). No correlation was found between TA and telomere length. A negative correlation existed between telomere length and age (r= −0.42; p=0.0097). The Kaplan-Meier statistical method and logrank test were used for univariate survival analysis and the Cox proportional hazard regression models for multivariate survival analysis. In multivariate analysis, when adjusted for age (>= 50 years versus younger), cytogenetics findings (poor prognosis versus others) and the nature of leukemia (secondary versus de novo), improved survival was found in patients with a combination of short telomere length (<7.6 Kb) and weak TA (<0.09, cut off point separating the upper tertile) and the worse survival was found in patients with long telomere length (>=7.6 Kb) and high TA (>=0.09) (hazard ratio=9.91; 95% CI: 1.75–56.03; p=0.01). Our results suggest that the combination of telomere length and telomerase activity can be considered as an independent prognostic factor for survival in patients with AML. Table 1: Patients characteristics Sex (no. of patients) * AML post solid tumor (n=7), post myelodysplastic syndrome (n=1), post chronic myeloid leukemia (n=1) M 18 F 22 Age (years) Median 50 Range 22–74 Leukocyte count (Giga/L) Median 24.2 Range 1.3–360 Bone marrow blast percentage Median 76.5 Range 20–99 FAB Classification (no. of patients) M0 6 M1 9 M2 5 M4–M5 12 M4Eo 3 M6 1 Biphenotypic AL 3 NK AML 1 Type of leukemia (no. of patients) De novo 31 Secondary 9* Prognosis (based on karyotype) Good 5 Intermediate 21 Poor 10 Missing 4

scholarly journals Exploratory study on the impact of switching to nilotinib in 18 patients with chronic myeloid leukemia in chronic phase with suboptimal response to imatinib

2016 ◽  
Vol 8 (1) ◽  
pp. 3-12 ◽  
Author(s):  
Sikander Ailawadhi ◽  
Luke P. Akard ◽  
Carole B. Miller ◽  
Anand Jillella ◽  
Daniel J. DeAngelo ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Primary Endpoint ◽  
Exploratory Study ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Study Drug ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Open Label ◽  
The Impact

Background: The phase II, exploratory, open-label Exploring Nilotinib BCR-ABL Effects (ENABL) study [ ClinicalTrials.gov identifier: NCT00644878] assessed the impact of switching to nilotinib therapy in patients with chronic myeloid leukemia in chronic phase (CML-CP) who had a suboptimal molecular response with imatinib. Methods: Patients with CML-CP who had previously achieved a complete cytogenetic response (CCyR), but had a suboptimal molecular response, with frontline imatinib therapy ( N = 18) were assigned to receive nilotinib 300 mg twice daily. The primary endpoint was the change in BCR-ABL1 transcript levels from baseline after 12 months; rates of major molecular response (MMR) and safety were also assessed. Results: At 3 months after switching to nilotinib, 10 of 17 (59%) evaluable patients had achieved MMR. At 12 months, 9 of 12 (75%) evaluable patients had achieved MMR, and the median BCR-ABL1 level among all patients remaining in the study was 0.020% on the International Scale (IS), equivalent to a 3.7-log reduction from the standardized IS baseline (primary endpoint). Adverse events (AEs) were typically grade 1/2 and manageable with dose interruptions. A total of three patients experienced serious study drug-related AEs, including pancreatitis, bradycardia, and vertigo. No deaths were reported. Conclusions: Overall, results from this exploratory study suggest that switching to nilotinib due to suboptimal molecular response with imatinib can result in improved molecular response for patients with CML-CP.

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