scholarly journals Prolonged Glucocorticoid Exposure Does Not Accelerate Telomere Shortening in Cultured Human Fibroblasts

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1425
Author(s):  
Anthony S. Zannas ◽  
Oksana Kosyk ◽  
Calvin S. Leung
Keyword(s):  
Telomere Length ◽  
Psychosocial Stress ◽  
Prolonged Exposure ◽  
Disease Risk ◽  
Human Fibroblasts ◽  
Stress Hormones ◽  
In Vivo Studies ◽  
Biological Aging ◽  
Telomere Shortening

Psychosocial stress, especially when chronic or excessive, can increase disease risk and accelerate biological aging. Although the underlying mechanisms are unclear, in vivo studies have associated exposure to stress and glucocorticoid stress hormones with shorter telomere length. However, the extent to which prolonged glucocorticoid exposure can shorten telomeres in controlled experimental settings remains unknown. Using a well-characterized cell line of human fibroblasts that undergo gradual telomere shortening during serial passaging in culture, we show that prolonged exposure (up to 51 days) to either naturalistic levels of the human endogenous glucocorticoid cortisol or the more potent synthetic glucocorticoid dexamethasone is not sufficient to accelerate telomere shortening. While our findings await extension in other cell types and biological contexts, they indicate that the in vivo association of psychosocial stress with telomere shortening is unlikely to be mediated by a direct and universal glucocorticoid effect on telomere length.

Anti-Diabetic Retinopathy Potential of Noni: The beneficial effect and possible mechanism

2020 ◽  
Vol 3 (1) ◽  
pp. 01-21
Author(s):  
Faisal Ali
Keyword(s):  
Diabetic Retinopathy ◽  
Prolonged Exposure ◽  
Morinda Citrifolia ◽  
In Vivo Studies ◽  
Laboratory Research ◽  
Tropical Region ◽  
Bioactive Substances ◽  
High Blood Glucose

Noni (Morinda citrifolia L.) is being evaluated in laboratory research for its benefits as an antioxidant and immunity booster, as well as for its properties to prevent tumors and cure diabetes. The vast spread of Noni in tropical region of the globe, from America reaching to Africa and Southeast Asia, contributed in enhancing its usage and potency due to the diversity in harvest zone. Noni parts comprise fruits, seeds, leaves, and flowers are being used for individual nutritional and therapeutical values. Nevertheless, the fruit is widely characterized to contain the most valuable bioactive substances. On the other hand, diabetic retinopathy (DR) is a microvascular disorder impacting the small blood vessels in the retina, which includes microaneurysms, retinal hemorrhages, and hard exudates results from prolonged exposure to high blood glucose levels. The anti-diabetes effect of Noni extract and juice has been examined but the beneficial role of Noni and its potential mechanisms against the development of diabetic retinopathy phenotype is still ambiguous. This review, therefore, will discusses in details the pharmacological actions of M. citrifolia fruit, along with their isolated phytochemical compounds on diabetic retinopathy markers, through describing the conducted in vitro and in vivo studies as well as clinical data.

Restoration of telomeres in human papillomavirus-immortalized human anogenital epithelial cells

1994 ◽  
Vol 14 (2) ◽  
pp. 961-969
Author(s):  
A J Klingelhutz ◽  
S A Barber ◽  
P P Smith ◽  
K Dyer ◽  
J K McDougall
Keyword(s):  
Human Papillomavirus ◽  
Epithelial Cells ◽  
Telomere Length ◽  
Open Reading Frames ◽  
Population Doubling ◽  
Telomere Shortening ◽  
Human Papillomavirus Type 16 ◽  
Immortalized Cells ◽  
E6 And E7

Loss of telomeres has been hypothesized to be important in cellular senescence and may play a role in carcinogenesis. In this study, we have measured telomere length in association with the immortalization and transformation of human cervical and foreskin epithelial cells by the human papillomavirus type 16 or 18 E6 and E7 open reading frames. By using a telomeric TTAGGG repeat probe, it was shown that the telomeres of precrisis normal and E6-, E7-, and E6/E7-expressing cells gradually shortened with passaging (30 to 100 bp per population doubling). Cells that expressed both E6 and E7 went through a crisis period and gave rise to immortalized lines. In contrast to precrisis cells, E6/E7-immortalized cells generally showed an increase in telomere length as they were passaged in culture, with some later passage lines having telomeres that were similar to or longer than the earliest-passage precrisis cells examined. No consistent association could be made between telomere length and tumorigenicity of cells in nude mice. However, of the three cell lines that grew in vivo, two had long telomeres, thus arguing against the hypothesis that cancer cells favor shortened telomeres. Our results indicate that arrest of telomere shortening may be important in human papillomavirus-associated immortalization and that restoration of telomere length may be advantageous to cells with regard to their ability to proliferate.

33 TELOMERASE ACTIVITIES IN CLONED BEAGLE DOGS

2015 ◽  
Vol 27 (1) ◽  
pp. 109
Author(s):  
G. A. Kim ◽  
H. J. Oh ◽  
M. J. Kim ◽  
Y. K. Jo ◽  
E. M. N. Setyawan ◽  
...  
Keyword(s):  
Telomere Length ◽  
Donor Cell ◽  
Telomerase Activity ◽  
Physiological Age ◽  
Biological Aging ◽  
Amplification Protocol ◽  
Donor Cells ◽  
Activity Measurements ◽  
Natural Breeding

Telomerase is important ribonucleoprotein for restoring telomere length from its own RNA template. Regarding cloned animals derived from somatic cell nuclear transfer (SCNT), interesting questions have been raised about whether the cloning process restores cellular telomerase activity undergone by their donor cells. The present study was conducted to determine the effects of cloning on telomerase activity in the dog and normality of telomerase activity in cloned dogs. Focusing our attention on differences in telomerase activity depending on the age, we analysed telomerase activity in dogs produced by natural breeding of various ages. Comparison of the telomerase activities of cloned dogs and those of dogs produced by natural breeding was also performed. For SCNT, 2 cell donors, 7- and 9-year-old beagles, were used and donor cells were isolated from ear skin. After establishing donor cell lines, the enucleated canine in vivo-matured oocytes and the cells were injected and fused by electrofusion. After 30 days from embryo transfer, pregnancy diagnosis was performed and 7 cloned dogs were produced on the due date. For standardization of telomerase activity in beagles produced by natural breeding, blood of total 14 dogs at each age (10 months, 20 months, 5, 7, and 8 years old) were collected and telomerase activity was measured by the telomeric repeat amplification protocol (TRAP) assay. Telomerase activity measurements of at least 6 replications in each dog were performed. For statistical analysis, one-way ANOVA with Dunn's Multiple Comparison Test was used. Significant differences in telomerase activity were observed between the blood of cloned and donor dogs. It was shown that mean telomerase activities were decreased according to biological aging with significances. Mean telomerase activities in 10 cloned dogs were higher than those of a donor dog. Cloned dogs also showed similar levels of telomerase activities as their age-matched natural bred dogs, suggesting that they are within the variation in normal dogs. These observations indicate that the cloning process restores the telomerase activity in the dog. Thus, complex regulation of telomerase activity during nuclear reprogramming may regulate and be involved in telomerase activity in cloned dogs. It remains to be determined whether telomere length is correlated with telomerase activity and if it accurately reflects the physiological age of cloned dogs.This study was supported by IPET (#311062–04–2-SB010), RDA (PJ008975022013), Research Institute for Veterinary Science, the BK21 program, Nestle Purina Korea, and TS Corporation.

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.

scholarly journals Restoration of telomeres in human papillomavirus-immortalized human anogenital epithelial cells.

1994 ◽  
Vol 14 (2) ◽  
pp. 961-969 ◽  
Author(s):  
A J Klingelhutz ◽  
S A Barber ◽  
P P Smith ◽  
K Dyer ◽  
J K McDougall
Keyword(s):  
Human Papillomavirus ◽  
Epithelial Cells ◽  
Telomere Length ◽  
Open Reading Frames ◽  
Population Doubling ◽  
Telomere Shortening ◽  
Human Papillomavirus Type 16 ◽  
Immortalized Cells ◽  
E6 And E7

Loss of telomeres has been hypothesized to be important in cellular senescence and may play a role in carcinogenesis. In this study, we have measured telomere length in association with the immortalization and transformation of human cervical and foreskin epithelial cells by the human papillomavirus type 16 or 18 E6 and E7 open reading frames. By using a telomeric TTAGGG repeat probe, it was shown that the telomeres of precrisis normal and E6-, E7-, and E6/E7-expressing cells gradually shortened with passaging (30 to 100 bp per population doubling). Cells that expressed both E6 and E7 went through a crisis period and gave rise to immortalized lines. In contrast to precrisis cells, E6/E7-immortalized cells generally showed an increase in telomere length as they were passaged in culture, with some later passage lines having telomeres that were similar to or longer than the earliest-passage precrisis cells examined. No consistent association could be made between telomere length and tumorigenicity of cells in nude mice. However, of the three cell lines that grew in vivo, two had long telomeres, thus arguing against the hypothesis that cancer cells favor shortened telomeres. Our results indicate that arrest of telomere shortening may be important in human papillomavirus-associated immortalization and that restoration of telomere length may be advantageous to cells with regard to their ability to proliferate.

scholarly journals Psychosocial Stressors and Telomere Length: A Current Review of the Science

2020 ◽  
Vol 41 (1) ◽  
pp. 223-245 ◽  
Author(s):  
Kelly E. Rentscher ◽  
Judith E. Carroll ◽  
Colter Mitchell
Keyword(s):  
Telomere Length ◽  
Psychosocial Stress ◽  
Psychosocial Stressors ◽  
Biological Aging ◽  
Future Research ◽  
Age Related ◽  
Social Adversity ◽  
Wide Range ◽  
Increase Risk ◽  
Behavioral Mechanisms

A growing literature suggests that exposure to adverse social conditions may accelerate biological aging, offering one mechanism through which adversity may increase risk for age-related disease. As one of the most extensively studied biological markers of aging, telomere length (TL) provides a valuable tool to understand potential influences of social adversity on the aging process. Indeed, a sizeable literature now links a wide range of stressors to TL across the life span. The aim of this article is to review and evaluate this extant literature with a focus on studies that investigate psychosocial stress exposures and experiences in early life and adulthood. We conclude by outlining potential biological and behavioral mechanisms through which psychosocial stress may influence TL, and we discuss directions for future research in this area.

scholarly journals The effect of long-term ultra-endurance exercise and SOD2 genotype on telomere shortening with age

2020 ◽  
Vol 129 (4) ◽  
pp. 873-879 ◽  
Author(s):  
Barbara Hernando ◽  
Marta Gil-Barrachina ◽  
Elena Tomás-Bort ◽  
Ignacio Martinez-Navarro ◽  
Eladio Collado-Boira ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Endurance Training ◽  
Telomere Length ◽  
Endurance Exercise ◽  
Biological Aging ◽  
Acute Inflammatory Response ◽  
Telomere Shortening ◽  
Ultra Endurance ◽  
First Time

Habitual ultra-endurance exercise seems to promote telomere length maintenance, especially at older ages. In addition, the beneficial effect of ultra-endurance training on biological aging is higher in ultra-trail runners who have been engaged to ultra-endurance training during many years. Finally, and for the first time, this study shows that the SOD2 rs4880 polymorphism has a significant impact on telomere length, as well as on acute inflammatory response to a 107-km trail race.

scholarly journals THER-15. DEVELOPING TUMOR-HOMING CYTOTOXIC HUMAN INDUCED NEURAL STEM CELL THERAPY FOR BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i13-i14
Author(s):  
Alison Mercer-Smith ◽  
Wulin Jiang ◽  
Juli Bago ◽  
Simon Khagi ◽  
Carey Anders ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Drug Carrier ◽  
Human Fibroblasts ◽  
Genetically Engineered ◽  
In Vivo Studies ◽  
Tumor Homing ◽  
The Brain

Abstract INTRODUCTION: Non-small cell lung cancer (NSCLC) and breast cancer are the most common cancers that metastasize to the brain. New therapies are needed to seek out and eradicate metastases. Genetically engineered neural stem cells (NSCs) have shown unique tumor-homing capacity, allowing them to deliver cytotoxic proteins directly to tumors. An ideal NSC drug carrier would be readily available and autologous. We have transdifferentiated human fibroblasts into induced NSCs (hiNSCs) that home to tumors and engineered the hiNSCs to release the cytotoxic protein TRAIL. Here we used intracerebroventricular (ICV) injections to deliver hiNSCs to metastatic foci. METHODS: We performed an in vitro efficacy co-culture assay, used in vivo studies to determine the migration, persistence, and efficacy of therapeutic hiNSCs against H460 NSCLC and triple-negative breast cancer MB231-Br tumors in the brain. Following the establishment of tumors in the brains of nude mice, hiNSCs were injected directly into the tumor or the ventricle contralateral to the site of tumor. The migration and persistence of hiNSCs was investigated by following the bioluminescence of the hiNSCs. The therapeutic efficacy of the hiNSCs was determined by following the bioluminescece of the tumor. RESULTS/CONCLUSION: Co-culture results demonstrated that hiNSC therapy reduced the viability of H460 and MB231-Br up to 75% and 99.8% respectively compared to non-treated controls. ICV-administered hiNSC serial imaging show that cells persisted for more than one week. Fluorescent analysis of tissue sections showed that hiNSCs co-localized with lateral and a contralateral tumors within 7 days. Using H460 and MB231-Br models, kinetic tracking of intracranial tumor volumes showed intratumoral or ICV-injected therapeutic hiNSCs reduced the growth rate of brain tumors by 31-fold and 3-fold, respectively. This work demonstrates for the first time that we can effectively deliver personalized cytotoxic tumor-homing cells through the ventricles to target brain metastases.

scholarly journals Association Between Dietary Selenium Intake and Leukocyte Telomere Length in a Nationally Representative Sample of US Adults (OR11-06-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Buyun Liu ◽  
Yangbo Sun ◽  
Guifeng Xu ◽  
Shuang Rong ◽  
Wei Bao
Keyword(s):  
Telomere Length ◽  
Representative Sample ◽  
Quantitative Polymerase Chain Reaction ◽  
Antioxidant Properties ◽  
Biological Aging ◽  
Leukocyte Telomere Length ◽  
Telomere Shortening ◽  
Dietary Selenium ◽  
Selenium Intake ◽  
Nationally Representative

Abstract Objectives DNA damage induced by oxidative stress is implicated in accelerated telomere shortening, a biomarker of biological aging. Although selenium has antioxidant properties, its impact on telomere length is largely unknown. This study aimed to examine the association between dietary selenium intake and leukocyte telomere length in a nationally representative sample of US adults. Methods We included 7409 adults aged 20 years or older who participated in the National Health and Nutrition Examination Survey (NHANES) 1999–2002. Dietary selenium intake was calculated using data collected in the 24-hour dietary recall. Leukocyte telomere length was assayed using the quantitative polymerase chain reaction method. The association between selenium intake and telomere length was estimated by weighted linear regression models adjusting for demographic, socioeconomic and lifestyle factors, body mass index, supplements intake, and leukocyte cell type composition. Results The average dietary selenium intake was 109.1 mg/d (standard error [SE] 1.15). We didn't find a significant association between dietary selenium intake and telomere length in US adults. The average telomere length (SE) was 1.01 (0.02), 1.01 (0.01), and 1.04 (0.01) across increasing tertiles of dietary selenium intake. However, a significant interaction was observed for age (P = 0.02). Among individuals aged 20–44 years, the β coefficient of log-transformed telomere length, compared to lowest tertile of dietary selenium intake, was −0.041 (SE 0.012, P = 0.002) and −0.033 (SE 0.018, P = 0.07) for middle tertile and the highest tertile of selenium intake, respectively. The corresponding β coefficient was 0.009 (SE 0.016, P = 0.59) and −0.001 (SE 0.012, P = 0.95), respectively, for adults 45–64 years old, and 0.017 (SE 0.015, P = 0.28) and 0.059 (SE 0.021, P = 0.01), respectively, for those aged 65 years or older. The results were not appreciably changed even after additionally adjustment for dietary intake of vitamin A, vitamin E, and zinc. Conclusions The association between dietary selenium intake and telomere length differed significantly by age groups, indicating that higher selenium intake may prevent telomere shortening in older adults but not in younger or middle-aged adults. Further studies about the underlying mechanisms are warranted. Funding Sources NA.

Topographical analysis of telomere length and correlation with genomic instability in whole mount prostatectomies

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11107-11107
Author(s):  
A. M. Joshua ◽  
P. Marrano ◽  
A. Evans ◽  
T. Van der Kwast ◽  
M. Zielenska ◽  
...  
Keyword(s):  
Telomere Length ◽  
Chromosomal Instability ◽  
Chromosomal Abnormalities ◽  
Chromosome 8 ◽  
Telomere Maintenance ◽  
Current Evidence ◽  
Telomere Shortening ◽  
Whole Mount ◽  
Trisomy 7

11107 Background: Many critical events in prostatic carcinogenesis appear to relate to the emergence of chromosomal instability and acquisition of genomic rearrangements. Characteristic abnormalities such as 8p loss, 8q gain, trisomy 7, PTEN microdeletions and TMPRSS2-ERG gene fusions appear to mediate mechanisms to increase neoplastic transformation in prostate cancer. Current evidence suggests that telomere dysfunction is a likely causative factor for some of these abnormalities on the basis of its relationship to mechanisms such as the break-fusion-bridge cycle that can lead to the onset of chromosomal instability. Methods: In this study, we correlated telomere length in various prostatic histologies by quantitative FISH with genomic markers of chromosomal instability by standard FISH and immunohistochemical measures of proliferation in 3 whole mount prostatectomies. Results: After analysing approximately 25,000 cells, we found that telomere shortening was correlated with an increase in the number of cells with abnormalities on chromosome 8, such as an increase in the average number of c-myc signals (r∼0.35, p∼0.02). However, there were no significant correlations with abnormalities such as trisomy 7 or abnormalities of the PTEN locus in any sample. Additional findings included; associations found with the probability of C-MYC aberrations in stroma with greater proximity to cancer (<1,000 um), a correlation between telomere length in a number of prostatic histologies (normal, atrophy, HPIN and cancer) with the adjacent stroma, and a lack of correlation between the Ki67 index of various histologies and their telomere length - all suggesting the importance of microenvironmental effects on telomere maintenance in the prostate. Finally, we also report significant telomere shortening in BPH in 2 cases, a phenomenon that has not been noted previously. Conclusions: This is the first study to directly link a mechanism of chromosomal instability with specific chromosomal abnormalities in prostatic carcinogenesis and also suggests that the microenvironmental milieu is of critical importance in the evolution of in vivo telomere homeostasis. No significant financial relationships to disclose.

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