The Impact of Lifestyle on Sperm Telomere Length and Telomerase Activity in Men Undergoing IVF Treatments

Author(s):  
2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Madhuri Tolahunase ◽  
Rajesh Sagar ◽  
Rima Dada

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.


2010 ◽  
Vol 22 (1) ◽  
pp. 239
Author(s):  
W. Garrels ◽  
W. Kues ◽  
U. Baulain ◽  
H. Niemann

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.


2021 ◽  
Vol 14 (02) ◽  
pp. 891-901
Author(s):  
Lavanya Prathap ◽  
Prathap Suganthirababu S ◽  
Praveen Kumar K ◽  
Preetha S

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.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4262-4262
Author(s):  
Veronique Saada ◽  
Pierre Tran Ba Loc ◽  
Camille Legeai ◽  
Marine Castaing ◽  
Jean-Henri Bourhis ◽  
...  

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


2018 ◽  
Vol 373 (1741) ◽  
pp. 20160442 ◽  
Author(s):  
Dan T. A. Eisenberg ◽  
Christopher W. Kuzawa

Telomeres are repeating DNA found at the ends of chromosomes that, in the absence of restorative processes, shorten with cell replications and are implicated as a cause of senescence. It appears that sperm telomere length (TL) increases with age in humans, and as a result offspring of older fathers inherit longer telomeres. We review possible mechanisms underlying this paternal age at conception (PAC) effect on TL, including sperm telomere extension due to telomerase activity, age-dependent changes in the spermatogonial stem cell population (possibly driven by ‘selfish’ spermatogonia) and non-causal confounding. In contrast to the lengthening of TL with PAC, higher maternal age at conception appears to predict shorter offspring TL in humans. We review evidence for heterogeneity across species in the PAC effect on TL, which could relate to differences in statistical power, sperm production rates or testicular telomerase activity. Finally, we review the hypothesis that the PAC effect on TL may allow a gradual multi-generational adaptive calibration of maintenance effort, and reproductive lifespan, to local demographic conditions: descendants of males who reproduced at a later age are likely to find themselves in an environment where increased maintenance effort, allowing later reproduction, represents a fitness improving resource allocation. This article is part of the theme issue ‘Understanding diversity in telomere dynamics’.


2020 ◽  
Vol 1 ◽  
Author(s):  
Waylon J. Hastings ◽  
Dan T.A. Eisenberg ◽  
Idan Shalev

Abstract Technical challenges associated with telomere length (TL) measurements have prompted concerns regarding their utility as a biomarker of aging. Several factors influence TL assessment via qPCR, the most common measurement method in epidemiological studies, including storage conditions and DNA extraction method. Here, we tested the impact of power supply during the qPCR assay. Momentary fluctuations in power can affect the functioning of high-performance electronics, including real-time thermocyclers. We investigated if mitigating these fluctuations by using an uninterruptible power supply (UPS) influenced TL assessment via qPCR. Samples run with a UPS had significantly lower standard deviation (p < 0.001) and coefficient of variation (p < 0.001) across technical replicates than those run without a UPS. UPS usage also improved exponential amplification efficiency at the replicate, sample, and plate levels. Together these improvements translated to increased performance across metrics of external validity including correlation with age, within-person correlation across tissues, and correlation between parents and offspring.


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