Effects of paternal pre-conceptional n-3 polyunsaturated fatty acids on telomere length in the offspring / 公共卫生与预防医学

Objective To investigate the effects of paternal pre-conceptional n-3 polyunsaturated fatty acids (n-3 PUFAs) on telomere length (TL) in the offspring. Methods Three to four-week old male C57 BL/6J mice (Father) were randomly divided into three groups and fed either an n-3 PUFA-deficient (n-3 D) (n-6:n-3 PUFA ratio = 47.2:1) diet, a diet with normal n-3 PUFA content (n-3 N) (n-6:n-3 PUFA ratio = 4.3:1), or a diet with high n-3 PUFA content (n-3 H) (n-6:n-3 ratio = 1.5:1), for 12 weeks. Then, the offspring were generated by mating the father mice with 12-week-old virgin female C57 BL/6J mice. The TL, mRNA expression of telomere transcriptase and binding proteins, as well as DNA methylation in the TERT promoter region were determined in adult offspring mice. Results Compared to n-3 N diet, paternal feeding with n-3 D diet during preconception decreased offspring TL in the peripheral blood cells, liver, adipose tissue and brain, accompanied by upregulated hepatic mRNA expression of TIN2 in the female, and downregulated hepatic expression of TERC, and binding proteins TRF2 and POT1a in the male. Meanwhile, paternal n-3 D diet shortened testis TL in offspring instead of themselves, with altered mRNA expression of TERT and binding proteins TRF1, TRF2 and POT1a. Paternal n-3 H diet showed no differences in effects on offspring TL and expressions of TERC and binding proteins with n-3 N diet, but normalized the alterations in associated parameters resulted from paternal n-3 D diet. In addition, although paternal n-3 D or n-3 H diet did not affect testis TL in themselves compared to n-3 N diet, fathers fed n-3 H diet had longer testis TL and higher expression of TRF1, TRF2, POT1a and RAP1 than those fed n-3 D diet. Finally, the DNA methylation fraction in the TERT promoter in offspring testes and male offspring liver was no difference between paternal n-3 D and n-3 N diet groups. CpG sites with altered methylation were less (1 site) between paternal n-3 H and n-3 N diet groups than those (5 sites) between paternal n-3 H and n-3 D diet groups in male offspring liver and testes. Conclusion Maintaining paternal optimal n-3 PUFA status in pre-conception increases offspring TL, probably mediated by inheritance from increased TL in father and regulation on expressions of telomere transcriptase and binding proteins in the offspring, which may be helpful for promoting offspring development and disease prevention in adulthood.

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Telomere length, oxidative and epigenetic changes in blood DNA of patients with exacerbated psoriasis vulgaris

Abstract Background The pathogenesis of psoriasis vulgaris involves changes in DNA molecules, genomic instability, telomere attrition, and epigenetic alterations among them. These changes are also considered important mechanisms of aging in cells and tissues. Objective This study dealt with oxidation damage, telomere length and methylation status in DNA originating from peripheral blood of 41 psoriatic patients and 30 healthy controls. Methods Oxidative damage of serum DNA/RNA was determined immunochemically. Real-time PCR was used for the analysis of the telomere length. ELISA technique determined levels of 5-methylcytosine in blood cells' DNA. Results Oxidative damage of serum DNA/RNA was higher in patients than in controls (median, 3758 vs. 2286 pg/mL, p < 0.001). A higher length of telomeres per chromosome was found in patients whole-cell DNA than in controls (3.57 vs. 3.04 kilobases, p = 0.011). A negative correlation of the length of telomeres with an age of the control subjects was revealed (Spearman's rho = -0.420, p = 0.028). Insignificantly different levels of 5-methylcytosine in patients and controls were observed (33.20 vs. 23.35%, p = 0.234). No influences of sex, smoking, BMI, PASI score, and metabolic syndrome on the methylation status were found. Study limitations i) A relatively small number of the participants, particularly for reliable subgroup analyses, ii) the Caucasian origin of the participants possibly influencing the results of the parameters determined, and iii) Telomerase activity was not directly measured in serum or blood cells. Conclusion The study demonstrated increased levels of oxidized DNA/RNA molecules in the serum of patients with exacerbated psoriasis vulgaris. The results were minimally influenced by sex, the presence of metabolic syndrome, or cigarette smoking. In the psoriatic blood cells' DNA, the authors observed longer telomeres compared to healthy controls, particularly in females. Insignificantly higher global DNA methylation in psoriasis cases compared to the controls indicated marginal clinical importance of this epigenetic test performed in the blood cells' DNA.

Impact of Culture Temperature Changes on the Efficacy of Growth Inhibitory Manipulation of Cancer Cell Lines / 日本温泉気候物理医学会雑誌

  We have previously reported that high-temperature (42°C) culture inhibited the proliferation of human umbilical endothelial cells (HUVECs). We described how the proliferative capacity and telomere length (TL)-related parameters of HUVECs, one of somatic cells, change with culture temperature. It was speculated that a combination of cytostatic manipulations, such as anticancer treatments, and high-temperature conditions would more effectively suppress the growth of somatic cells. Therefore, we hypothesized that increasing the core body temperature (BT) as a pretreatment for cancer treatment enhances the effectiveness of cancer treatment. In the present study, various cells (HUVECs, Jurkat cells, and SLVL) were cultured under different temperature conditions (35°C, 37°C or 39°C) combined with anticancer manipulations (X-ray irradiation or addition of 1-β-D-Arabinofuranosylcytosine [Ara-C]), which resulted in changes in the proliferation rate and TL. The degree of cell proliferation inhibitory effect depended on the combination of cell type, anticancer procedure, and temperature condition. Therefore, the best therapeutic condition might be selected in advance by checking the proliferation rate of biopsied cancer cells being cultured under combinations of anticancer manipulations at altered temperature conditions.

Lamin B1 regulates the growth of hepatocellular carcinoma cells by influencing telomerase activity / 生物工程学报

Lamin B1 (LMNB1) is highly expressed in liver cancer tissues, and its influence and mechanism on the proliferation of hepatocellular carcinoma cells were explored by knocking down the expression of the protein. In liver cancer cells, siRNAs were used to knock down LMNB1. Knockdown effects were detected by Western blotting. Changes in telomerase activity were detected by telomeric repeat amplification protocol assay (TRAP) experiments. Telomere length changes were detected by quantitative real-time polymerase chain reaction (qPCR). CCK8, cloning formation, transwell and wound healing were performed to detect changes in its growth, invasion and migration capabilities. The lentiviral system was used to construct HepG2 cells that steadily knocked down LMNB1. Then the changes of telomere length and telomerase activity were detected, and the cell aging status was detected by SA-β-gal senescence staining. The effects of tumorigenesis were detected by nude mouse subcutaneous tumorigenesis experiments, subsequent histification staining of tumors, SA-β-gal senescence staining, fluorescence in situ hybridization (FISH) for telomere analysis and other experiments. Finally, the method of biogenesis analysis was used to find the expression of LMNB1 in clinical liver cancer tissues, and its relationship with clinical stages and patient survival. Knockdown of LMNB1 in HepG2 and Hep3B cells significantly reduced telomerase activity, cell proliferation, migration and invasion abilities. Experiments in cells and tumor formation in nude mice had demonstrated that stable knockdown of LMNB1 reduced telomerase activity, shortened telomere length, senesced cells, reduced cell tumorigenicity and KI-67 expression. Bioinformatics analysis showed that LMNB1 was highly expressed in liver cancer tissues and correlated with tumor stage and patient survival. In conclusion, LMNB1 is overexpressed in liver cancer cells, and it is expected to become an indicator for evaluating the clinical prognosis of liver cancer patients and a target for precise treatment.

Study on the correlation between telomere dysfunction of human gastric mucosa and chronic atrophic gastritis / 中华消化杂志

Objective:To investigate the correlation between telomere dysfunction of human gastric mucosa and chronic atrophic gastritis (CAG).Methods:From February 12, 2019 to July 10, 2020, at Endoscopy Center, Guang′anmen Hospital, China Academy of Chinese Sciences, 30 patients received endoscopy and pathological diagnosed with CAG (CAG group) were collected, and 30 patients with chronic non-atrophic gastritis (CNAG) were collected at the same time (CNAG group). The relative telomere length was detected by real time fluorescent quantitative polymerase chain reaction. The expression of telomere repeat binding factor (TRF) 1, TRF2 and protection of telomere (POT) 1 at protein level were detected by immunohistochemical staining and semi-quantitative analysis. Spearman analysis was used to analyze the correlation between the relative telomere length of gastric mucosa and the protein expression levels of TRF1, TRF2 and POT1. Mann-Whitney U test and independent sample t test were used for statistical analysis. Results:The relative telomere length of the gastric mucosa in the CAG group was shorter than that in the CNAG group (0.67 (0.51 to 1.17) vs. 1.06(0.69 to 1.37)), and the difference was statistically significant ( U=297.00, P=0.024). The protein expression levels of TRF1, TRF2, and POT1 in the CAG group were all higher than those in the CNAG group, respectively (4.26±2.49 vs. 1.86±1.34, 10.12±2.76 vs. 8.78±2.81, 4.22±2.48 vs. 2.53±1.62), and the differences were statistically significant ( t=8.05, 3.23, 5.39; P<0.001, =0.001, and <0.001). In the CAG group, the protein expression levels of TRF2 and POT1 in gastric mucosa were negatively correlated with the relative telomere length ( r=-0.477 and -0.417, P=0.008 and 0.022). Conclusions:The telomere dysfunction is related to the pathogenesis of CAG. The change of telomere binding protein expression level is involved in the shortening of telomere and pathological process of CAG patients.

Correlation of telomere length of bone marrow mononuclear cells with relapse after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia / 白血病·淋巴瘤

Objective:To investigate the relationship between telomere length of bone marrow mononuclear cells and prognosis of patients with acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Telomere length of bone marrow mononuclear cells before transplantation, after transplantation and before donor mobilization as well as information related to follow-up of 33 AML patients who received allo-HSCT in the Affiliated Hospital of Guizhou Medical University between June 2020 and June 2021 were retrospectively analyzed. Telomere length was detected by using telomeric terminal restriction fragment (TRF) method. Telomere length was compared among patients with different prognoses. The recurrence within 1 year was treated as the gold standard and receiver operating characteristic (ROC) curve was used to analyze the effect of telomere length before transplantation or before donor mobilization in the judgement of the recurrence within 1 year after transplantation. The patients were stratified according to the optimal threshold value of telomere length for patients or donors, and Kaplan-Meier method was used to compare the progression-free survival (PFS) of patients with different stratification, and log-rank test was performed.Results:The median age of 33 patients was 34 years (14-61 years), and there were 17 males and 16 females; 31 patients were initially diagnosed with AML, 1 patient transferred from myelodysplastic syndrome (MDS) to AML, and 1 patient transferred from chronic granulocytic leukemia (CML) to AML; 14 received identical sibling transplantation and 19 received haploidentical sibling transplantation. The median age of the donors was 30 years (20-65 years), including 24 males and 9 females. Telomere length of bone marrow mononuclear cells before mobilization in 33 donors was longer than that in patients before transplantation (33 cases) and at +30 d after transplantation (31 cases) [(6.67±0.31) kb, (6.40±0.33) kb, (6.48±0.33) kb, respectively; all P < 0.05], and the difference between patients before and at +30 d after transplantation was not statistically significant ( t = 0.89, P = 0.378), and the telomere length of bone marrow mononuclear cells in 11 patients +180 d after transplantation was (6.66±0.18) kb. The incidence of acute graft-versus-host disease (aGVHD) after transplantation was 45.5% (15/33), the incidence of infection with clear imaging and pathogenic basis was 39.4% (13/33), the mortality rate within 1 year after transplantation was 3.0% (1/33), and the recurrence rate within 1 year after transplantation was 15.2% (5/33). There were no statistically significant differences in telomere length of donor pre-mobilization bone marrow mononuclear cells between the groups with and without aGVHD and between the infected and non-infected groups (all P > 0.05).Compared with patients who had not relapsed within 1 year after transplantation, telomere length of donor pre-mobilization bone marrow mononuclear cells was shorter in patients who relapsed within 1 year after transplantation [(6.39±0.19) kb vs. (6.72±0.30) kb, t = -3.23, P = 0.011], telomere length was longer in patients before transplantation [(6.75±0.16) kb vs. (6.35±0.36) kb, t = 4.17, P = 0.001]. ROC curve analysis showed that the optimal threshold values for telomere length of pre-transplantation and donor pre-mobilization bone marrow mononuclear cells were 6.48 and 6.42 kb, respectively for patients who relapsed within 1 year after transplantation. PFS in patients with pre-transplantation bone marrow mononuclear cells telomere length < 6.48 kb was better than that in patients with telomere length ≥ 6.48 kb ( P = 0.003); PFS in patients with pre-mobilization bone marrow mononuclear cells telomere length>6.42 kb was better than that in patients with telomere length ≤ 6.42 kb ( P < 0.001). Conclusions:In allo-HSCT for AML, patients have an increased risk of relapse within 1 year after transplantation when their pre-transplantation bone marrow mononuclear cells telomere length is long and the donor bone marrow mononuclear cells telomere length is short.

Research progress on shortened telomere length in newborns and impaired cardiovascular metabolic health in children caused by exposure to cadmium during pregnancy / 环境与职业医学

Cadmium exposure during pregnancy is a non-negligible public health problem which may increase the risk of shortened telomere length in newborns and cardiovascular metabolic health damage in children, and has attracted attention from many researchers in recent years. This article reviewed recent studies both domestically and internationally on the associations among cadmium exposure during pregnancy, shortened telomere length in newborns, and cardiovascular metabolic abnormalities in children, and briefly outlined possible mechanisms of shortened telomere length in newborns by cadmium exposure during pregnancy. Current research results showed that cadmium exposure during pregnancy is related to shortened telomere length in newborns and cardiovascular metabolic abnormalities in children, and shortened telomere length in newborns is also related to cardiovascular metabolic abnormalities in children. It suggested that telomere length in newborns may be a biomarker reflecting cardiovascular metabolic abnormalities in children caused by cadmium exposure during pregnancy. In addition, the current potential mechanisms of cadmium exposure during pregnancy accelerating neonatal telomere length shortening include inflammatory reaction, mitochondrial dysfunction, antioxidant consumption/antioxidant enzyme inactivation, and DNA methylation, and these biological mechanisms are associated with cardiovascular metabolic abnormalities through certain factors, such as obesity, elevated blood pressure, impaired fasting blood glucose, and dyslipidemia in children, suggesting that cardiovascular metabolic abnormalities in children may be programmed in early life, but there are still few relevant studies. In the future, research should be conducted on the association among cadmium exposure during pregnancy, telomere length, and offspring cardiovascular metabolism, as well as possible mediating efficacy and related biological mechanisms of telomere length, aiming to provide early-life biological information for the prevention of cardiovascular and metabolic diseases.

Advances of structure and mechanisms of bromodomain-containing protein 4 and its related research in tumors / 生物工程学报

The bromodomain and extraterminal domain (Bet) family are the regulators of the epigenome and also the pivotal driving factors for the expression of tumor related genes that tumor cells depend on for survival and proliferation. Bromodomain-containing protein 4 (Brd4) is a member of the Bet protein family. Generally, Brd4 identifies acetylated histones and binds to the promoter or enhancer region of target genes to initiate and maintain expression of tumor related genes. Brd4 is closely related to the regulation of multiple transcription factors and chromatin modification and is involved in DNA damage repair and maintenance of telomere function, thus maintaining the survival of tumor cells. This review summarizes the structure and function of Brd4 protein and the application of its inhibitors in tumor research.

Association between leukocyte telomere length and sex by quantile regression analysis

ABSTRACT Introduction: Telomere length (TL) is a biomarker of cellular proliferative history. In healthy individuals, leukocyte TL shortens with age and associates with the lifespan of men and women. However, most of studies had used linear regression models to address the association of the TL attrition, aging and sex. Methods: We evaluated the association between the TL, aging and sex in a cohort of 180 healthy subjects by quantile regression. The TL of nucleated blood cells was measured by fluorescent in situ hypridization (flow-FISH) in a cohort of 89 men, 81 women, and 10 umbilical cord samples. The results were validated by quantitative polymerase chain reaction (qPCR) and compared to a linear regression analysis. Results: By quantile regression, telomere dynamics slightly differed between sexes with aging: women had longer telomeres at birth and slower attrition rate than men until the sixth decade of life; after that, TL eroded faster and became shorter than that in men. These differences were not observed by linear regression analysis, as the overall telomere attrition rates in women and men were similar (42 pb per year, p < 0.0001 vs. 45 pb kb per year, p < 0.0001). Also, qPCR did not recapitulate flow-FISH findings, as the telomere dynamics by qPCR followed a linear model. Conclusion: The quantile regression analysis accurately reproduced a third-orderpolynomial TL attrition rate in both women and men, but it depended on the technique applied to measure TL. The Flow-FISH reproduced the expected telomere dynamics through life and, differently from the qPCR, was able to detect the subtle TL variations associated with sex and aging.

Telomeres Length Variations in a Rheumatoid Arthritis Patients Cohort at Early Disease Onset and after Follow-Up

ABSTRACT Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial joint inflammation, progressive disability, premature immune aging, and telomere length (TL) shortening. Objective: The objective of the study was to study TL changes in patients at early disease onset and after follow-up. Methods: Relative leukocyte TL (rLTL) was measured by quantitative polymerase chain reaction (qPCR) in 88 at-admission patients (AAP) with < 1 year of symptoms onset, self-compared after follow-up, and a reference group of sex- and age-matched healthy individuals. Correlations between rLTL percentage change after variable disease exposure time (DET) and clinical laboratory disease activity markers and treatments were assessed. Non-parametrical statistics were applied, considering < 0.05 p-value significant. Results: The median (p25, p75) rLTL was lower in patients after DET (0.61, 0.49-0.70) than in AAP (0.64, 0.50-0.77), p = 0.017. Furthermore, telomeres at early stages of RA were shorter than in the reference group (0.77, 0.59-0.92; p = 0.003). HLA-DRB1*04 allele carrier status did not significantly affect rLTL at an early stage and after follow-up. The patients' rLTL shortening was mainly associated with longer at-admission telomeres (OR 16.2, 95%CI: 3.5-74.4; p < 0.0001). Conclusion: At follow-up, RA patients showed significantly shorter rLTL than AAP, particularly in those AAP with longer telomeres, disregarding disease activity and treatments, denoting an rLTL shortening effect influenced by age, DET, and native rLTL.

Perceived stress and cellular aging among medical students: A cross-sectional study

Background: There is little evidence in medical students on the connection between stress and telomere length (TL), which represents cellular aging. Aim and Objective: We undertook this study to investigate the relationship between stress and cellular aging as measured by TL. Materials and Methods: After obtaining permission from the Institute Ethics Committee, apparently healthy subjects between the ages of 18 and 25 years were recruited. Subjects were excluded if they are on any medication, subjects with a history of diabetes, hypertension, endocrine disorders, kidney disease, and hypertensive patients using drugs. The study tool was the Kessler10 (K10) psychological distress instrument. TL was determined using a previously described real-time quantitative polymerase chain reaction technique. Results: The mean age of the participants was 19.23 ± 1.23 years. The data were divided based on K10 scores. Comparison was made between the K10 scores less than and more than 20. No significant difference in baseline characteristics was found except height. Further, there was no correlation between height with either TL or K10 scores. We found significantly lesser TL in individuals K10 score more than 20 (P < 0.00). Conclusion: Given the high association between stress levels and TL shortening in medical students, this may contribute to premature aging as well as the process of development of several illnesses associated with short TL.

Research update on the effect of adverse childhood experience on telomere morphology / 中国学校卫生

Abstract@#Adverse childhood experiences (ACEs) not only affect individual s physical and mental health but also have adverse intergenerational effects. A growing body of researches focused on biological mechanism of ACEs, among which the emerging role of telomere has gained much attention. This article reviews the association between ACEs and telomere morphology during different developmental stages and the role of telomere in adverse health effects of ACEs. It aims to summarize possible mechanisms underlying negative effects of ACEs.

Mediating effect of telomere length on relationship between lead and cadmium coexposure and blood glucose / 环境与职业医学

Background Individual lead or cadmium exposure can cause abnormal blood glucose level and changes in telomere length, and the role of telomere length in the relationship between heavy metal joint exposure and blood glucose level is still unclear. Objective To explore the role of telomere length in the relationship between lead and cadmium coexposure and blood glucose. Methods A cross-sectional study was conducted. By convenient sampling method, 600 residents living in two communities in a city in North China were selected as participants from April to June 2016. Face-to-face interviews were performed to collect general demographics and lifestyles of the participants. The peripheral blood samples of the participants were collected for blood glucose and telomere length detection, the urine samples were collected for urinary cadmium, urinary lead, and urinary creatinine measurement, and both urinary cadmium and urinary lead were corrected by urinary creatinine. The included participants were divided into a control group, a high-cadmium and low-lead group, a high-lead and low-cadmium group, and a high-lead and high-cadmium group, according to the median levels of urinary cadmium and urinary lead. A restricted cubic spline model was constructed to analyze the relationship between urinary lead/cadmium levels and blood glucose concentrations in the four groups and the relationship between cadmium exposure and telomere length in the high-lead and high-cadmium group. Intermediary model test was conducted to analyze the effect of telomere length on the relationship between exposures to lead and cadmium and blood glucose. Results The included participants were divided into the control group (n=99), the high-cadmium and low-lead group (n=91), the high-lead and low-cadmium group (n=145), and the high-lead and high-cadmium group (n=265). The differences in age, education level, per capita monthly household income, smoking, blood glucose, and telomere length were statistically significant among the four groups (P＜0.05). The high-lead and high-cadmium group had the highest blood glucose concentration, (5.63±1.68) mmol·L−1, and the shortest telomere length, (2.63±1.05) Kb. The restricted cubic spline results showed that urinary cadmium level was correlated with blood glucose concentration in the high-lead and high-cadmium group (F=3.45, P=0.037), and there was a non-linear association (F=6.91, P=0.002); the association between urinary cadmium level and telomere length was also non-linear (F=5.93, P=0.043). The intermediary model test results showed that telomere length was a mediating variable between urinary cadmium level and blood glucose concentration, and the mediating effect size was 0.0192 (95%CI: 0.0007-0.0563), with a mediation ratio of 15.57%. Conclusion Correlations between urinary cadmium and blood glucose and between urinary cadmium and telomere length were observed in the high-lead and high-cadmium coexposure group, and telomere length may play a mediating role in the relationship between them.

Telomere length: biological marker of cellular vitality, aging, and health-disease process

SUMMARY The aging process occurs due to the decline of vital physiological functions and adaptability of the body, being influenced by genetics and lifestyle. With advances in genetics, biological aging can be calculated by telomere length. Telomeres are regions at the ends of chromosomes that play a role in the maintenance and integrity of DNA. With biological aging, telomere shortening occurs, causing cellular senescence. Several studies show that shorter telomeres are associated with acute and chronic diseases, stress, addictions, and intoxications. Even in the current COVID-19 pandemic, telomere shortening is proposed as a marker of severity in individuals infected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). On the other hand, healthy lifestyle habits increase telomere length and balance of various cellular functions, preventing diseases.

Cost-Effective Trap qPCR Approach to Evaluate Telomerase Activity: an Important Tool for Aging, Cancer, and Chronic Disease Research

OBJECTIVES: Telomeres are a terminal "DNA cap" that prevent chromosomal fusion and degradation. However, aging is inherent to life, and so is the loss of terminal sequences. Telomerase is a specialized reverse transcriptase encoded by self-splicing introns that counteract chromosome erosion. Telomerase activity is observed during early embryonic development, but after the blastocyst stage, the expression of telomerase reduces. The consequences of either insufficient or unrestrained telomerase activity underscore the importance of ongoing studies aimed at elucidating the regulation of telomerase activity in humans. In the present study, we aimed to standardize a simplified telomerase repeat-amplification protocol (TRAP) assay to detect telomerase activity in unstimulated and PHA-stimulated mononuclear cells. METHODS and RESULTS: Our optimized qPCR-based can efficiently evaluate telomerase activity. Quantification of protein and DNA between unstimulated and PHA-stimulated peripheral blood mononuclear cells revealed cellular activation and cell-cycle entry. The assay also showed that relative telomerase activity is significantly different between these two conditions, supporting the applicability of the assay. Furthermore, our findings corroborated that telomerase activity decreases with age. CONCLUSIONS: Telomeres and telomerase are implicated in aging and development of chronic diseases and cancer; however, difficulty in accessing commercial kits to investigate these aspects is a critical constraint in health surveillance studies. Our optimized assay was successfully used to differentiate telomerase activity between unstimulated and stimulated cells, clearly showing the reactivation of telomerase upon cell activation. This assay is affordable, reproducible, and can be executed in resource-limited settings.

Clinical Application and Challenges of Telomere and Telomerase Research in Lung Cancer / 中国肺癌杂志

Lung cancer is one of the malignant tumors with high incidence rate and high mortality worldwide. Telomere and telomerase are closely related to the occurrence and development of lung cancer. Although telomerase may not be the direct cause of carcinogenesis, it plays a key role in maintaining telomere length and tumor growth. The length of most tumors, including lung cancer, is shortened. The change of telomere length is related to the risk of lung cancer, and may become the therapeutic target and predictive index. Target drugs for telomere and telomerase signaling pathway are constantly being explored, and drugs represented by telomerase inhibitors are expected to be used in clinical treatment of lung cancer in the future. However, the research on telomere and telomerase is far from enough. The bypass mechanism of telomere length maintenance may be the direction of further research.
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Telomere length and telomerase: early biomarkers for environmental carcinogen exposure / 中国职业医学

Telomere is a DNA-protein complex located at the end of linear chromosome of eukaryotic cells, which has the function of stabilizing chromosome. The change of telomere length is closely related to the exposure to environmental carcinogens. The repair and elongation of telomere rely on the catalysis and mediation of telomerase. Exposure to typical environmental carcinogens polycyclic aromatic hydrocarbons(PAHs) can affect the change of telomere length by regulating the expression of telomere-related genes. Long-term exposure to PAHs can shorten the telomeres of peripheral blood leukocytes in a dose-response relationship. Telomere dysfunction is one of the important mechanisms of arsenic poisoning. The change of telomere length can be used as a biomarker of arsenic exposure. However, there are differences in the research results on the effect of arsenic exposure on telomere length, so the consistency of the effect of arsenic exposure on telomere length and the possible mechanism need to be further studied. Exposure to atmospheric fine particulate matter can attack genetic material by inducing oxidative stress and inflammatory response in the body, and then affect the telomere length of cells in vivo. Acute particulate matter exposure can increase telomere length in a short time(a few hours to a few days), and subsequent telomere shortening may be related to the inflammatory mechanism. Telomere length and telomerase activity can be used as biomarkers and play an important role in monitoring early carcinogenesis, diagnosis and prognosis assessment of cancers caused by environmental carcinogens.

Mediating role of peripheral blood telomere length in relationship between environmental lead exposure and glomerular filtration rate / 环境与职业医学

Background Exposure to environmental lead can cause kidney damage and telomere wear. However, the relationship among lead, peripheral blood telomere length, and glomerular filtration rate (eGFR) are unclear. Objective This study is conducted to investigate the relationships of urinary lead level with peripheral blood telomere length and renal function index eGFR, and further explore whether peripheral blood telomere length plays an intermediary role in the relationship between urinary lead level and eGFR. Methods A case-control study was conducted to select 497 residents from two communities in a city, including 230 in the control group (eGFR≥80 mL·min−1) and 267 in the abnormal eGFR group (eGFR<80 mL·min−1). Basic information and health information of the subjects were collected through a face-to-face questionnaire survey. Fasting morning urine was collected, and urinary lead and urinary creatinine (UCr) were detected. Fasting peripheral venous blood was collected to detect telomere length and serum creatinine (SCr) in peripheral blood leukocytes. eGFR was estimated by the Levey formula. After further adjusting for age, gender, education level, family per capita monthly income, smoking, and drinking the relationship among urinary lead level, peripheral blood telomere length, and renal function index eGFR was evaluated by mediating effect analysis. Results The overall level of creatinine-adjusted urinary lead [M (P25, P75)] in the abnormal eGFR group was 3.85 (1.56, 7.34) μg·g−1 which was higher than that in the control group, 1.57 (0.60, 3.62) μg·g−1(P<0.001). In addition, the overall level of peripheral blood telomere length in the abnormal eGFR group was 2.42 (1.89, 3.10) Kb, lower than that in the control group, 2.69 (2.09, 3.64) Kb (P<0.001). The results of mediating effect analysis showed that the magnitude of mediating effect by peripheral blood telomere length was −0.276 (95%CI: −0.708-−0.001) and it contributed 3.35% to the relationship between urinary lead level and eGFR. In women, the magnitude of mediating effect by peripheral blood telomere length was −0.484 (95%CI: −1.160-−0.023) between urinary lead level and eGFR, and the proportion of the mediating effect was 5.34%. In men, no mediating role of peripheral blood telomere length was found between urinary lead and eGFR. Conclusion Urinary lead level is closely related to renal function index eGFR and telomere length in peripheral blood. Peripheral blood telomere length plays a mediating role in the relationship between female urinary lead and eGFR in women.

Acortamiento de telómeros en enfermedades neurodegenerativas: implicaciones terapéuticas / Telomere attrition in neurodegenerative disorders: therapeutic implications

Introducción: Varias enfermedades neurodegenerativas están asociadas a la ocurrencia de acortamiento de los telómeros, y los convierten en biomarcadores y dianas terapéuticas potenciales. Objetivo: Reflejar la relevancia del acortamiento de los telómeros para enfermedades neurodegenerativas, y destacar sus implicaciones Material y métodos: Se realizó una revisión bibliográfica durante los meses de septiembre de 2019 a enero de 2020. Fueron consultadas bases de datos de referencia, con el uso de descriptores y operadores booleanos. La estrategia de búsqueda avanzada para la selección de los artículos fue empleada, teniendo en cuenta la calidad metodológica o validez de los estudios. Desarrollo: Fueron identificadas evidencias sólidas de asociación entre el acortamiento de los telómeros y las enfermedades de Alzheimer y Huntington, que sugieren un papel relevante de la biología de los telómeros en la fisiopatología de estas enfermedades. Las evidencias disponibles hasta el momento no permiten establecer la relevancia de la biología de los telómeros en la fisiopatología de la Enfermedad de Parkinson o de la esclerosis lateral amiotrófica. Se obtuvieron evidencias de la utilidad de terapias orientadas a la prevención del acortamiento de los telómeros para el tratamiento de enfermedades neurodegenerativas. Conclusiones: El acortamiento de los telómeros es de relevancia fisiopatológica y clínica para las enfermedades de Alzheimer y Huntington, mientras que existen evidencias insuficientes para establecer su importancia en la Enfermedad de Parkinson y la esclerosis lateral amiotrófica. El uso de estrategias para estimular la actividad de la telomerasa tiene potenciales aplicaciones terapéuticas en el contexto de enfermedades neurodegenerativas(AU)

Introduction: Several neurodegenerative disorders are associated with telomere attrition, turning telomeres into potential biomarkers and potential therapeutic targets. Objective: To assess the relevance of telomere attrition for neurodegenerative disorders, highlighting its therapeutic implications. Material and methods: A literature review was carried out from September 2019 to January 2020. Several databases were searched by using descriptors and Boolean operators. Advanced search strategy was used for the selection of articles, taking into account the methodological quality and validity of the studies. Results: Strong evidence for an association between telomere attrition and Alzheimer and Huntington diseases was obtained, suggesting a potential importance of telomere biology in the physiopathology of these diseases. Current evidence does not allow establishing the relevance of telomere attrition in the physiopathology of Parkinson´s disease or Amyotrophic Lateral Sclerosis. Evidence was obtained for the usefulness of therapies for the prevention of telomere attrition in the treatment of neurodegenerative disorders. Conclusions: Telomere attrition has physiopathological and clinical relevance in Alzheimer´s and Huntington´s diseases, though current evidence is not enough to establish its role in Parkinson's disease and Amyotrophic Lateral Sclerosis. Strategies that enhance telomerase activity have therapeutic potential in the context of neurodegenerative disorders(AU)