Objectives Telomere length and its relationship to job stress among workers in the health sector in Indonesia, especially in Bali, have never been studied. The purpose of the study was to analyze the correlation of the telomere length and serotonin levels to job stress and the type of locus of control (LOC) among nurses who were running shift work.
Internal-External Control ; Occupational Stress ; Serotonin ; Telomere Shortening

Telomerase is an enzyme that maintains telomeres and prevents telomere shortening, and may be linked with cellular proliferation or the aging process. The purpose was to examine telomerase activity in human chorionic villi from early and term normal pregnancies, and to analyze the correlation of telomerase activity (TA) with MIB-1 & bcl-2. A total of 37 placentae were obtained from 16 early and 21 term pregnancies. TA was assayed by telomeric repeat amplification protocol, and immunohistochemical staining was performed for MIB-1 & bcl-2 expression. TA & MIB-1 expression were strong in early placenta, but bcl-2 was highly expressed in term placentae. Thirteen (81.25%) of 16 early placentae showed TA, but only 2 (9.52%) of 21 term placentae expressed TA (p<0.01). MIB-1 was observed in nuclei of cytotrophoblast, and the expression rate was 16.09% in early placentae and 2.87% in term placentae (p<0.01). bcl-2 was observed only in the cytoplasm of syncytiotrophoblast. Term placenta demonstrated stronger expression of bcl-2 compared to early placentae (p<0.05). These findings suggest that TA, MIB-1 & bcl-2 expression are critically regulated over the course of gestation: cytotrophoblast, main cells of early chorionic villi, may be a common source of telomerase and proliferative activity. The TA showed good correlation with cellular proliferative activity. Syncytiotrophoblast, may be a main source of bcl-2 expression which is stronger in the term placentae.
Aging ; Cell Proliferation ; Chorion* ; Chorionic Villi* ; Cytoplasm ; Humans* ; Placenta ; Pregnancy* ; Telomerase* ; Telomere ; Telomere Shortening ; Trophoblasts

PURPOSE: An attempt was made to investigate N-nitrosomorpholine (NNM) induced carcinogenic processes in rat liver. MATERIALS AND METHODS: Rats were fed with NNM (200 mg/l) for 7 weeks, after then stopped. Length of telomere and activity of telomerase were analyzed. Hepatocytes were isolated and grown on tissue culture. Heat shock was treated at 43oC, and patterns of cell death ere evaluted by fluorescent study. Nuclei and nucleoli were isolated for analysis of various signal molecules. RESULTS: Shortening of telomere length presented in NNM treated liver, but induction of telomerase was not found. Ex vivo hepatocytes from 10~12th week showed increased heat shock resistance at 43oC. NNM-treated hepatocytes exhibited heat shock induced cell death (necrosis) after 7 hours, whereas the control showed necrosis after 3 hours. The signal molecules related to nucleolar growth revealed increased expression which included B23, C23, p38, Erk1/2 and p120. Partial degradation of B23 and Erk2 was noted in necrosis of NNM treated hepatocytes induced by heat shock. CONCLUSION: The hepatocytes at the stage of 10~12th week in the stop experiment of NNM are situated in the tumour promotion. Those cells showed various metabolic alterations. We found that the increased growth related signals were accompanied with increased heat shock resistance, telomere shortening but no induction of telomerase.
Animals ; Cell Death ; Hepatocytes* ; Hot Temperature ; Liver ; Metabolism* ; Necrosis ; Rats* ; Shock ; Telomerase ; Telomere ; Telomere Shortening

PURPOSE: Sarcomas have rarely been analyzed for telomerase, which is an RNA-dependent DNA polymerase to maintain telomeres and prevent telomere shortening. This study was undertaken to determine telomerase activity and the expression of the telomerase subunits human telomerase RNA (hTR) and telomerase reverse transcriptase (TERT) in soft tissue sarcomas. MATERIALS AND METHODS: Twenty three sarcomas were analyzed for the telomerase activity by a radioactive PCR-based TRAP assay. All of the samples were further investigated for the expression of hTR by in situ hybridization and for TERT and p53 by immunohistochemistry. RESULTS: Telomerase activity was detected in four (17%) samples. Expression of hTR was demonstrated in 11 (48%) cases, whereas TERT was expressed in 20 (87%).Of the four telomerase-positive tumors, three were positive for both hTR and TERT, and one was positive only for TERT. p53 overexpression was observed in nine (39%) tumors. The frequency of p53 expression increased as the tumor grade advanced (p= .064). CONCLUSION: These data indicate that the reactivation of telomerase is an uncommon event in human soft tissue sarcomas. The high frequency of the expression of hTR and TERT in these tumors suggests that telomerase activity may be regulated at the transcriptional level and an additional event leading to telomerase activation exist.
Humans* ; Immunohistochemistry ; In Situ Hybridization ; RNA ; RNA-Directed DNA Polymerase ; Sarcoma* ; Telomerase* ; Telomere ; Telomere Shortening

PURPOSE: Telomeres, special protein and tandem repeat DNA structure that cap the ends of linear eukaryotic chromosomes, are essential for chromosome structure and stability. Human telomeric DNA is known to shorten by 30~200 bp with each somatic cell division. However, the phase of telomere changes has not been studied extensively. METHODS: Telomere length was analyzed in the peripheral blood mononuclear cells (PBMCs) of 39 normal controls aged from newborn to 72 years by Southern blot hybridization using PharMingen's TeloQunatTM Telomere Length Assay Kit (Becton Dickinson Co.). RESULTS: The mean telomere length of the population was 9.68 kb (range, 5.65~14.40 kb). The length (kb) decreased with age (A) by the following regression: T=10.86 0.04 A (T=telomere length in kb; A=age in years) (r= 0.38; P=0.016). The mean telomere lengths according to age groups were: 10.26 kb for less than 15 years; 9.92 kb for 16 to 40 years; 8.03 kb for over 40 years. The telomere length of over 40 years was significantly shorter than that of less than 15 years (P=0.013), and than that of 16 to 40 years (P=0.011). The phase of telomere changes was evaluated by age subgroups. The shortening was fastest in individuals of age <5, while the length showed a plateau or slight increment in age group between 5 to 35. The length decreased steadily with age by the regression of 12.43+/-0.07 A (r= 0.500; P=0.034) in age group over 35. CONCLUSION: Telomere length of PBMCs decreases with age, and the different phase of telomere length shortening may suggest that the shortening of telomere is not a constant process over lifespan, but a dynamic process that is differently regulated in age groups.
Blotting, Southern ; Cell Division ; Chromosome Structures ; DNA ; Humans ; Infant, Newborn ; Tandem Repeat Sequences ; Telomere Shortening* ; Telomere*

Previous studies have established a correlation between increasing chronological age and risk of cirrhosis. This pattern raised interest in the role of telomeres and the telomerase complex in the pathogenesis of liver fibrosis and cirrhosis. This review aims to summarize and analyze the current understanding of telomere regulation in hepatocytes and lymphocytes and how this ultimately relates to the development of liver fibrosis. Notably, in chronic viral hepatitis, telomere shortening in hepatocytes and lymphocytes occurs in such a way that may promote further viral replication while also leading to liver damage. However, while telomere shortening occurs in both hepatocytes and lymphocytes and ultimately results in cellular death, the mechanisms of telomere loss appear to be initiated by independent processes. The understanding of telomere maintenance on a hepatic and immune system level in both viral and non-viral etiologies of cirrhosis may open doors to novel therapeutic strategies.
Fibrosis ; Hepatitis ; Hepatocytes ; Immune System ; Liver Cirrhosis ; Liver Diseases* ; Liver* ; Lymphocytes ; Telomerase ; Telomere Shortening ; Telomere*

Cell aging is an extremely complex process, which is characterized by mitochondrial structural dysfunction, telomere shortening, inflammatory microenvironment, protein homeostasis imbalance, epigenetic changes, abnormal DNA damage and repair, etc. Aging is usually accompanied by structural and functional damage of tissues and organs which further induces the occurrence and development of aging-related diseases. Aging includes physiological aging caused by increased age and pathological aging induced by a variety of factors. Noteworthy, as a target organ directly contacting with the outside air, lung is more prone to various stimuli, causing pathological premature aging which is lung aging. Studies have found that there is a certain proportion of senescent cells in the lungs of most chronic respiratory diseases. However, the underlying mechanism by which these senescent cells induce lung senescence and their role in chronic respiratory diseases is still obscure. This paper focuses on the causes and classification of lung aging, the internal mechanism of lung aging involved in chronic respiratory diseases, and the application of anti-aging treatments in chronic respiratory diseases. We hope to provide new research ideas and theoretical basis for the clinical prevention and treatment in chronic respiratory diseases.
Aging/pathology* ; Cellular Senescence ; Humans ; Lung/pathology* ; Lung Diseases/pathology* ; Respiration Disorders/pathology* ; Telomere ; Telomere Shortening

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.
Animals ; Mice ; Telomerase/metabolism* ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Telomere Shortening ; In Situ Hybridization, Fluorescence ; Mice, Nude ; Telomere/pathology* ; Carcinogenesis

Macroautophagy/autophagy is a conserved degradation system that engulfs intracytoplasmic contents, including aggregated proteins and organelles, which is crucial for cellular homeostasis. During aging, cellular factors suggested as the cause of aging have been reported to be associated with progressively compromised autophagy. Dysfunctional autophagy may contribute to age-related diseases, such as neurodegenerative disease, cancer, and metabolic syndrome, in the elderly. Therefore, restoration of impaired autophagy to normal may help to prevent age-related disease and extend lifespan and longevity. Therefore, this review aims to provide an overview of the mechanisms of autophagy underlying cellular aging and the consequent disease. Understanding the mechanisms of autophagy may provide potential information to aid therapeutic interventions in age-related diseases.
Aged ; Aging ; Autophagy ; Cell Aging ; DNA Damage ; Homeostasis ; Humans ; Longevity ; Neurodegenerative Diseases ; Organelles ; Oxidative Stress ; Telomere Shortening

PURPOSE: Prenatal maternal stress affects offspring's atopic dermatitis (AD) development, which is thought to be mediated by the oxidative stress. We aimed to evaluate the difference in leukocyte telomere length (LTL), a marker for exposure to oxidative stress, according to the prenatal stress exposure and the later AD development. METHODS: From a birth cohort (the COhort for Childhood Origin of Asthma and allergic diseases) that had displayed a good epidemiologic association between the exposure to prenatal stress and AD development in the offspring, we selected 68 pairs of samples from 4 subject groups based on the level of prenatal maternal stress and later AD development. The LTL was measured from both cord blood and 1-year peripheral blood, and their LTLs were compared between subject groups. Finally, the proportion of AD development was examined in the subject groups that are reclassified based on subjects' exposure to prenatal stress and there LTL. RESULTS: Cord-blood LTL was shorter in prenatally stressed infants than in unstressed ones (P = 0.026), which difference was still significant when subjects became 1 year old (P = 0.008). LTL of cord blood, as well as one of the 1-year peripheral blood, was not different according to later AD development at 1 year (P = 0.915 and 0.174, respectively). Shorter LTL made no increase in the proportion of later AD development in either prenatally high-stressed or low-stressed groups (P = 1.000 and 0.473, respectively). CONCLUSIONS: Cord-blood LTL may reflect subjects' exposure to maternal prenatal stress. However, the LTL shortening is not a risk factor of increasing AD development until the age of 1, and a longer investigation may be necessary for validation. Currently, the results doubt the role of LTL shortening as a marker for risk assessment tool for the prenatal stress associated with AD development in the offspring.
Asthma ; Child ; Cohort Studies ; Dermatitis, Atopic ; Fetal Blood ; Humans ; Infant ; Leukocytes ; Oxidative Stress ; Parturition ; Risk Assessment ; Risk Factors ; Stress, Psychological ; Telomere Shortening ; Telomere