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1.
Ecotoxicol Environ Saf ; 182: 109453, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31349105

RESUMO

Telomeres are DNA-protein structures that protect chromosome ends from degradation and fusion, which are shortened by oxidative stress, for example air pollution including benzene, toluene, Coke Oven Emissions (COEs), and so on. As a biomarker of health and disease, telomere length is associated with cardiovascular, diabetes and cancers. The aim of this study was to estimate the effects of COEs exposure on telomere length and the benchmark dose (BMD) of COEs. A total of 542 coke oven workers and 235 healthy controls without exposure to toxicants were recruited. Quantitative PCR was used to determine the telomere length in human peripheral blood leukocytes DNA. Propensity scoring was used to match coke oven workers to healthy controls. Linear regression models and trend tests were used to the relationship between COEs exposure and telomere length. Telomere length in COEs exposed group 0.764 (0.536, 1.092) was significantly shorter than that in the control group 1.064(0.762, 1.438), (P < 0.001). There were significantly dose-response relationships between COEs exposure and telomere damage with telomere length as a biomarker. A BMDL value lower than the present occupational exposure limits (OELs) of COEs exposure was evaluated using the BMD approach in coke oven workers. Our results suggested that shorter telomere length is related to occupational exposure to COEs and the level of COEs exposure lower than the current national OELs in China and many other countries could induce telomere damage.


Assuntos
Poluentes Ocupacionais do Ar/análise , Coque/análise , Exposição Ocupacional/análise , Telômero/efeitos dos fármacos , Adolescente , Adulto , Poluentes Ocupacionais do Ar/toxicidade , Benchmarking , Biomarcadores/análise , Estudos de Casos e Controles , China , Coque/toxicidade , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Telômero/ultraestrutura , Adulto Jovem
2.
Actas dermo-sifiliogr. (Ed. impr.) ; 110(3): 212-219, abr. 2019. tab, ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-181711

RESUMO

Introducción y objetivos: La telomerasa es una enzima implicada en el mantenimiento de los telómeros y la senescencia celular. Numerosos estudios han demostrado que en más del 90% de las neoplasias malignas se detecta actividad telomerásica. El objetivo del presente estudio es analizar la expresión de telomerasa por inmunohistoquímica en una serie de neoplasias melanocíticas. Material y métodos: Estudio observacional retrospectivo realizado en una serie de 85 melanomas primarios, 12 metastásicos y 22 nevus melanocíticos. La expresión de telomerasa se analizó empleando el anticuerpo monoclonal hTERT (Rockland). El análisis de los datos se realizó con el programa SPSS. Resultados: En todas las neoplasias melanocíticas analizadas se demostró expresión de telomerasa. En el caso de los melanomas predominó el patrón de expresión heterogéneo, y la expresión moderada o intensa. En los nevus resultó más frecuente una expresión homogénea con intensidad leve. El patrón de expresión heterogéneo se asoció a los melanomas de rápido crecimiento (p = 0,028), con Breslow > 4 mm (p = 0,004), con mitosis (p = 0,032), y con mutaciones en el gen TERT (p = 0,002). En el caso de los nevus, la intensidad fue menor en los nevus intradérmicos, seguidos de los compuestos y de los diplásicos (p = 0,054). Conclusiones: La expresión de telomerasa está presente en la totalidad de las neoplasias melanocíticas, con mayor expresión en los melanomas que en los nevus. En el caso de los melanomas, la expresión de forma heterogénea se asocia a un fenotipo de mayor agresividad


Background and objectives: Telomerase is an enzyme involved in maintaining the length of telomeres and cell senescence. Numerous studies have shown that in more than 90% of malignant tumors telomerase activity is detected. Material and methods: Retrospective observational study in a series of 85 cases of primary melanomas, 12 metastatic melanomas, and 22 melanocytic nevi. We used the monoclonal antibody hTERT (human telomerase reverse transcriptase, Rockland) to assess telomerase activity. The SPSS software package was used to analyze data. Results: Telomerase expression was present in all the melanocytic neoplasms analyzed. Expression was heterogenous and moderate or high in the melanomas. In contrast, expression was homogeneous and lower in the nevi. Heterogeneous expression was associated with rapid melanoma growth (P = .028), a Breslow thickness of more than 4 mm (P = .004), mitosis (P = .032), and mutations in the TERT gene (P = .002). Activity was less intense in intradermal nevi, and more intense in compound and dysplastic nevi (P = .054). Conclusions: Telomerase expression is found in all melanocytic neoplasms but is higher in melanomas than in nevi. A heterogeneous pattern of expression in melanomas is associated with more aggressive tumors


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Telomerase/análise , Neoplasias Cutâneas/diagnóstico , Melanoma/diagnóstico , Neoplasias Cutâneas/enzimologia , Telômero/ultraestrutura , Melanoma/enzimologia , Neoplasias Cutâneas/patologia , Telomerase/metabolismo , Imuno-Histoquímica , Estudos Retrospectivos , Anticorpos Monoclonais/administração & dosagem , Nevo/enzimologia
3.
Med Hypotheses ; 122: 1-4, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30593387

RESUMO

A stronger motivation to cultivate social ties in older adults (ages range from 62 to 86 years) has been associated with a cortisol profile similar to that observed in undergraduate students, who are decades younger. We have shown the cultivation of social networks buffers against increases in diurnal cortisol common in old age. Cortisol is crucial for the response to stress and the process of ageing, and a recent study has demonstrated that a lower cortisol level is associated with longevity. We link the findings of social network cultivation and cortisol profile to the processes of biological ageing through DNA telomere length. Telomeres are repeated DNA sequences that cap and protect the ends of chromosomes, and telomere length is considered a potential biomarker for biological age because it is closely related to the cellular process of ageing and chronic stress and is inversely related to chronological age. Studies examining biological ageing have shown an association between an altered cortisol profile and telomere length dynamics. Together, these findings on social networks, cortisol profiles and telomere length suggest that seniors who are motivated to maintain social ties are biologically younger. We therefore propose the 'rejuvenation hypothesis', which posits that seniors with a stronger motivation for social network cultivation are biologically younger, as measured by cortisol levels and telomere length, than their peers who are less motivated to pursue social relationships. This idea suggests a new perspective and potentially fruitful direction for geriatric research. The focus on social network cultivation adds an important psychosocial dimension to rejuvenation therapies that so far have been dominated by biomedical approaches. The rejuvenation hypothesis also has important implications for social policy by supporting the viability of promoting network cultivation among the elderly to facilitate healthy ageing.


Assuntos
Envelhecimento , Hidrocortisona/sangue , Rejuvenescimento , Comportamento Social , Rede Social , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Longevidade , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Telômero/ultraestrutura , Encurtamento do Telômero , Adulto Jovem
4.
Am J Clin Nutr ; 108(3): 453-475, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30535086

RESUMO

Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectional meta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Study-specific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a -3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI: -10.03, -5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10(-3) unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10(-3), -1.01 × 10(-3)) difference in age- and sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10(-3) unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10(-3), -1.25 × 10(-3)). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL are warranted.


Assuntos
Índice de Massa Corporal , Encurtamento do Telômero/fisiologia , Telômero/ultraestrutura , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Grupos Étnicos , Humanos , Leucócitos/ultraestrutura , Masculino , Pessoa de Meia-Idade , Obesidade/patologia , Fatores Sexuais
5.
Nutr Hosp ; 35(3): 570-575, 2018 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-29974764

RESUMO

INTRODUCTION: inflammation and oxidative stress are factors that may play a substantial role in telomere attrition. In line of this, obesity is associated with telomere shortening. Green tea had anti-inflammatory and antioxidant effects and may alter telomere length (TL). OBJECTIVES: we evaluated the effect of decaffeinated green tea supplementation in obese women on TL. METHODS: we conducted a cross-sectional interventional study with ten obese (body mass index [BMI] > 40 kg/m²) and eight normal weight (BMI > 18.5 and < 24.9 kg/m²) women (age between 27 and 48 years). The supplementation was carried out with capsules (each contained 450.7 mg of epigallocatechin-3-gallate) during eight weeks. Anthropometric and dietary intake assessment, and blood collection (for biochemical and TL analysis by quantitative PCR) were performed before and after supplementation. Normal weight patients were evaluated at a single moment. RESULTS: we observed a significant increase on TL after supplementation (1.57 ± 1.1 to 3.2 ± 2.1 T/Sratio; p < 0.05). Moreover, we found shorter TL in obese patients (day 0) when compared to normal weight individuals (3.2 ± 1.9 T/Sratio; p < 0.05) and an inverse association between TL and BMI, even after age adjustment (beta = -0.527; r² = 0.286; IC = -0.129, -0.009). CONCLUSION: obesity is related to shorter telomeres. Green tea supplementation during eight weeks promotes telomere elongation in obese women.


Assuntos
Catequina/análogos & derivados , Suplementos Nutricionais , Leucócitos/ultraestrutura , Obesidade/dietoterapia , Chá , Telômero/ultraestrutura , Adulto , Índice de Massa Corporal , Catequina/farmacologia , Estudos Transversais , Feminino , Humanos , Leucócitos/efeitos dos fármacos , Pessoa de Meia-Idade , Obesidade/sangue , Telômero/efeitos dos fármacos , Encurtamento do Telômero
6.
Med Hypotheses ; 116: 28-29, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29857903

RESUMO

There may exist an association between thyroid dysfunction/autoimmunity and parity. Autoimmune thyroiditis shows some degree of telomere shortening. Parity was recently found to be associated with telomere shortening. We hypothesize that among the factors affecting the tentative association between parity and thyroid dysfunction/autoimmunity shortened telomeres' may also be implicated. This could also be another facet of the processes leading to autoimmune thyroiditis.


Assuntos
Autoimunidade/genética , Telômero/ultraestrutura , Doenças da Glândula Tireoide/genética , Aborto Espontâneo , Biópsia por Agulha Fina , Feminino , Humanos , Modelos Teóricos , Paridade , Reação em Cadeia da Polimerase , Gravidez , Complicações na Gravidez , Tireoidite Autoimune/genética
7.
Nutr. hosp ; 35(3): 570-575, mayo-jun. 2018. graf, tab
Artigo em Inglês | IBECS | ID: ibc-180113

RESUMO

Introduction: inflammation and oxidative stress are factors that may play a substantial role in telomere attrition. In line of this, obesity is associated with telomere shortening. Green tea had anti-inflammatory and antioxidant effects and may alter telomere length (TL).Objectives: we evaluated the effect of decaffeinated green tea supplementation in obese women on TL. Methods: we conducted a cross-sectional interventional study with ten obese (body mass index [BMI] > 40 kg/m²) and eight normal weight (BMI > 18.5 and < 24.9 kg/m²) women (age between 27 and 48 years). The supplementation was carried out with capsules (each contained 450.7 mg of epigallocatechin-3-gallate) during eight weeks. Anthropometric and dietary intake assessment, and blood collection (for biochemical and TL analysis by quantitative PCR) were performed before and after supplementation. Normal weight patients were evaluated at a single moment. Results: we observed a significant increase on TL after supplementation (1.57 ± 1.1 to 3.2 ± 2.1 T/Sratio; p < 0.05). Moreover, we found shorter TL in obese patients (day 0) when compared to normal weight individuals (3.2 ± 1.9 T/Sratio; p < 0.05) and an inverse association between TL and BMI, even after age adjustment (beta = -0.527; r² = 0.286; IC = -0.129, -0.009).Conclusion: obesity is related to shorter telomeres. Green tea supplementation during eight weeks promotes telomere elongation in obese women


Introducción: la inflamación y el estrés oxidativo son factores que pueden jugar un papel importante en el desgaste de los telómeros. En línea con esto, la obesidad está asociada con el acortamiento de los telómeros. El té verde tiene efectos antiinflamatorios y antioxidantes y puede alterar la longitud de los telómeros (LT). Objetivos: evaluamos el efecto de la suplementación de té verde descafeinado en la LT en mujeres obesas. Métodos: realizamos un estudio intervencionista de corte transversal con 10 mujeres obesas (IMC > 40 kg/m²) y 8 con peso normal (IMC > 18,5 y < 24,9 kg/m²) (edad entre 27 y 48 años). La suplementación se llevó a cabo con cápsulas (cada una contenía 450,7 mg de epigalocatequina- 3-galato) durante 8 semanas. La evaluación de la ingesta antropométrica y dietética y la recolección de sangre (para análisis bioquímicos y LT por PCR cuantitativa) se realizaron antes y después de la administración de suplementos. Los pacientes de peso normal fueron evaluados en un solo momento. Resultados: observamos un aumento significativo en LT después de la suplementación (1,57 ± 1,1 a 3,2 ± 2,1 T/S ratio; p < 0,05). Además, encontramos LT más corta en pacientes obesos (día 0) en comparación con individuos de peso normal (3,2 ± 1,9 T/S ratio; p < 0,05) y una asociación inversa entre LT e IMC, incluso después del ajuste de edad (beta = -0,527; r² = 0,286; IC = -0,129, -0,009). Conclusión: la obesidad está relacionada con los telómeros más cortos. La administración de suplementos de té verde durante 8 semanas promueve la elongación de los telómeros en mujeres obesas


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Catequina/análogos & derivados , Suplementos Nutricionais , Leucócitos/ultraestrutura , Obesidade/dietoterapia , Chá , Telômero/ultraestrutura , Índice de Massa Corporal , Catequina/farmacologia , Estudos Transversais , Leucócitos , Obesidade/sangue , Telômero , Encurtamento do Telômero
8.
Iran Biomed J ; 22(4): 231-6, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29704891

RESUMO

Background: Telomeres are evolutionary, specialized terminal structures at the ends of eukaryotic chromosomes containing TTAGGG repeats in human. Several human diseases have been known to be associated with dramatic changes in telomere length. The aim of the present study was to assess the correlation between the relative leukocyte telomere length (LTL) and infertility in a group of Iranian azoospermic males. Methods: : In this case-control pilot study, relative telomere length (RTL) of peripheral blood leukocytes from a total of 30 idiopathic non-obstructive azoospermic males and 30 healthy fertile males was evaluated using real-time PCR. RTL was calculated as T (telomere)/S (single copy gene) ratio and compared between infertile and fertile groups. Results: Patients with azoospermia showed significantly shorter RTL than fertile males (0.54 vs. 0.84, p < 0.05). The area under the receiver operating characteristic (ROC) curve was estimated to be 99.8%, suggesting LTL as a potential marker for the diagnosis of azoospermia. Conclusion: Our findings demonstrated a probable association between telomere shortening and azoospermia in a population of Iranian infertile men affected by idiopathic azoospermia.


Assuntos
Azoospermia/diagnóstico , Azoospermia/genética , Leucócitos/citologia , Telômero/ultraestrutura , Adulto , Estudos de Casos e Controles , DNA/análise , Hormônio Foliculoestimulante/sangue , Humanos , Irã (Geográfico) , Cariotipagem , Estudos Longitudinais , Hormônio Luteinizante/sangue , Masculino , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real
9.
Free Radic Res ; 52(6): 639-647, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29589779

RESUMO

In skeletal muscle, which mainly contains postmitotic myonuclei, it has been suggested that telomere length remains roughly constant throughout adult life, or shortens in response to physiopathological conditions in muscle diseases or in the elderly. However, telomere length results from both the replicative history of a specific tissue and the exposure to environmental, DNA damage-related factors, therefore the predictive biological significance of telomere measures should combine the analysis of the various interactive factors. In the present study, we analysed any relationship between telomere length [mean and minimum terminal restriction fragment (TRF) length] chronological age, oxidative damage (4-HNE, protein carbonyls), catalase activity, and heat shock proteins expression (αB-crystallin, Hsp27, Hsp90) in semitendinous muscle biopsies of 26 healthy adult males between 20 and 50 years of age, also exploring the influence of regular exercise participation. The multiple linear regression analysis identified age, 4-HNE, catalase, and training status as significant independent variables associated with telomere length and jointly accounting for ∼30-36% of interindividual variation in mean and/or minimum TRF length. No association has been identified between telomere length and protein carbonyl, αB-crystallin, Hsp27, and Hsp90, as well as between age and the variables related to stress response. Our results showed that skeletal muscle from healthy adults displays an age-dependent telomere attrition and that oxidised environment plays an age-independent contribution, partially influenced by exercise training.


Assuntos
Aldeídos/metabolismo , Catalase/metabolismo , Exercício , Músculo Esquelético/metabolismo , Telômero/ultraestrutura , Adulto , Fatores Etários , Biomarcadores/metabolismo , Biópsia , Catalase/genética , Expressão Gênica , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Carbonilação Proteica , Cadeia B de alfa-Cristalina/genética , Cadeia B de alfa-Cristalina/metabolismo
10.
Nat Commun ; 9(1): 557, 2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29422501

RESUMO

Understanding the intricacies of telomerase regulation is crucial due to the potential health benefits of modifying its activity. Telomerase is composed of an RNA component and reverse transcriptase. However, additional factors required during biogenesis vary between species. Here we have identified fission yeast Lar7 as a member of the conserved LARP7 family, which includes the Tetrahymena telomerase-binding protein p65 and human LARP7. We show that Lar7 has conserved RNA-recognition motifs, which bind telomerase RNA to protect it from exosomal degradation. In addition, Lar7 is required to stabilise the association of telomerase RNA with the protective complex LSm2-8, and telomerase reverse transcriptase. Lar7 remains a component of the mature telomerase complex and is required for telomerase localisation to the telomere. Collectively, we demonstrate that Lar7 is a crucial player in fission yeast telomerase biogenesis, similarly to p65 in Tetrahymena, and highlight the LARP7 family as a conserved factor in telomere maintenance.


Assuntos
Proteínas Nucleares/genética , Fosfoproteínas/genética , Proteínas de Protozoários/genética , RNA Fúngico/genética , DNA Polimerase Dirigida por RNA/genética , RNA/genética , Ribonucleoproteínas/genética , Schizosaccharomyces/genética , Telomerase/genética , Motivos de Aminoácidos , Sequência Conservada , Expressão Gênica , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Ligação Proteica , Proteínas de Protozoários/metabolismo , RNA/metabolismo , Estabilidade de RNA , RNA Fúngico/metabolismo , DNA Polimerase Dirigida por RNA/metabolismo , Ribonucleoproteínas/metabolismo , Schizosaccharomyces/metabolismo , Telomerase/metabolismo , Telômero/química , Telômero/ultraestrutura , Tetrahymena thermophila/genética , Tetrahymena thermophila/metabolismo
11.
BMJ Open ; 8(2): e018792, 2018 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-29472262

RESUMO

INTRODUCTION: Chronic stress has adverse effects on health. Adults and children from low-income families are subject to multiple sources of stress. Existing literature about economic hardship mostly focuses on either adults or children but not both. Moreover, there is limited knowledge on the relationship between parental generalised stress and child health problems. This study aims to explore the bidirectional relationship between parental stress and child health in Chinese low-income families and to identify other modifiable factors influencing this relationship. METHODS AND ANALYSIS: This prospective cohort study will sample 254 low-income parent-child pairs and follow them up for 24 months with assessments at three time points (baseline, 12 and 24 months) on parental stress, health-related quality of life (HRQOL) and child health and behaviour using both subjective measures and objective physiological parameters. This study will collect data using standardised measures on HRQOL and behaviours of children as well as on HRQOL, mental health and stress levels of parents along with physiological tests of allostatic load and telomere length. The mediating or moderating effect of family harmony, parenting style and neighbourhood conditions will also be assessed. Data will be analysed using latent growth modelling and cross-lagged path analysis modelling to examine the bidirectional effect of parental stress and child health over time. Mediation and moderation analysis will also be conducted to examine the mechanism by which the variables relate. ETHICS AND DISSEMINATION: This study was approved by the institutional review board of the University of Hong Kong-the Hospital Authority Hong Kong West Cluster, reference no: UW 16-415. The study findings will be disseminated through peer-reviewed publications and international conferences. TRIAL REGISTRATION NUMBER: NCT03185273; Pre-results.


Assuntos
Saúde da Criança , Pais/psicologia , Pobreza , Qualidade de Vida , Estresse Psicológico/epidemiologia , Adolescente , Adulto , Criança , Feminino , Hong Kong , Humanos , Estudos Longitudinais , Masculino , Relações Pais-Filho , Estudos Prospectivos , Projetos de Pesquisa , Características de Residência , Telômero/ultraestrutura
12.
J Pediatr Hematol Oncol ; 40(1): 1-6, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28452859

RESUMO

Neuroblastomas (NB) are one of the most common extracranial solid tumors in children, and they frequently display high heterogeneity in the disease course. With ongoing research, more information regarding the genetic etiology and molecular mechanisms underlying these contrasting phenotypes is being uncovered. The proto-oncogene MYCN is amplified in approximately 20% of NB cases and is considered a indicator of poor prognosis and an indicator of high-risk NB. The poor prognosis of high risk NB is incompletely explained by MYCN amplification. Recently, massive parallel sequencing studies reported several relatively common gene alterations, such as ATRX mutation and TERT rearrangement that are involved in telomere maintenance through telomerase activity and alternative lengthening of telomeres. Thus, these are important for understanding the etiology and molecular pathogenesis of NB, and hence, for identifying diagnostic and treatment markers. Development of telomerase inhibitors and identification of alternative lengthening of telomeres related targets will contribute to the individualized treatment for high-risk NB. In this mini-review, we will discuss the research progress of TERT-mediated and ATRX-mediated telomere maintenance and NB, especially high-risk tumors.


Assuntos
Neuroblastoma/genética , Telomerase/fisiologia , Telômero/metabolismo , Proteína Nuclear Ligada ao X/fisiologia , Humanos , Neuroblastoma/etiologia , Neuroblastoma/patologia , Neuroblastoma/ultraestrutura , Prognóstico , Telômero/ultraestrutura
13.
Cytogenet Genome Res ; 153(2): 96-104, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29186711

RESUMO

The genus Colomesus is the sole representative of the family Tetraodontidae in the Amazon region. Here, Colomesus asellus was analyzed using conventional and molecular cytogenetic protocols. Its diploid chromosome number is 2n = 46 with 12 meta-, 10 submeta-, 16 subtelo-, and 8 acrocentric chromosomes and a fundamental number of FN = 84. An XX/XY sex chromosome system was identified. Mapping of 18S rDNA correlated with the nucleolus organizer regions (Ag-NORs) in the short arms of the 2 X chromosomes in females and in the Y chromosome in males. C-banding revealed heterochromatin in the centromeric regions of all chromosomes, except for pair 3. Prominent sex chromosome-specific heterochromatin amplification was observed, covering the short arms of the Y chromosome almost entirely. FISH with telomeric and tropomyosin (tpm1) sequences, respectively, revealed terminal signals in all chromosomes. The analysis of extended DNA fibers confirmed the colocalization and the interspersed pattern of the telomeric and tpm1 sequences. Thus, this study highlights the remarkable evolutionary dynamism presented by the Amazonian puffer fish regarding the differentiation of a heteromorphic XY sex chromosome system and a particular sex-specific amplification of rDNA sites. This is the first record of such an association in the Tetraodontidae family.


Assuntos
Cromossomos Sexuais/genética , Processos de Determinação Sexual , Tetraodontiformes/genética , Animais , Antígenos Nucleares/genética , Brasil , Bandeamento Cromossômico , DNA Ribossômico/genética , Feminino , Amplificação de Genes , Hibridização in Situ Fluorescente , Masculino , RNA Ribossômico 18S/genética , Sequências Repetitivas de Ácido Nucleico , Telômero/genética , Telômero/ultraestrutura , Tropomiosina/genética
14.
Int J Sports Med ; 38(14): 1111-1116, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29100249

RESUMO

Emergent evidence suggests that the long-term healthy lifestyle of master athletes may attenuate aging. We compared telomere length (TL) of high-level master sprinters and non-athlete age-matched controls, and analyzed the relationships of TL with performance and body fat. Elite master sprinters (n=11; aged 50.1±9.2yrs) and healthy untrained controls (n=10; aged 45.4±10.9yrs) had blood samples collected for biochemical and biomolecular analyses. Master sprinters had longer TL, lower body fat and BMI, and a better lipid profile than age-matched controls (p<0.05). A large effect size was verified comparing TL between athletes vs. controls (Cohen's d=1.039), with a significant negative correlation between TL and performance decline per decade (r=-0.624, p<0.01) and a positive correlation of TL and actual performance level (r=0.641, p<0.01). In conclusion, TL of elite master sprinters was longer than their untrained peers, and seems to be not only a marker of health status, but also an indicator of sports longevity since both actual performance level and its decrease over years were related to TL. Further research might assess the TL of elite master endurance athletes for comparison with sprinters, and also investigate the underlying mechanisms by which the attenuation of telomere shortening occurs in master athletes.


Assuntos
Atletas , Desempenho Atlético , Composição Corporal , Corrida , Telômero/ultraestrutura , Adulto , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade
15.
Elife ; 62017 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-28980942

RESUMO

Background: Shorter childhood telomere length (TL) and more rapid TL attrition are widely regarded as manifestations of stress. However, the potential effects of health interventions on child TL are unknown. We hypothesized that a water, sanitation, handwashing (WSH), and nutritional intervention would slow TL attrition during the first two years of life. Methods: In a trial in rural Bangladesh (ClinicalTrials.gov, NCT01590095), we randomized geographical clusters of pregnant women into individual water treatment, sanitation, handwashing, nutrition, combined WSH, combined nutrition plus WSH (N + WSH), or control arms. We conducted a substudy enrolling children from the control arm and the N + WSH intervention arm. Participants and outcome assessors were not masked; analyses were masked. Relative TL was measured at 1 and 2 years after intervention, and the change in relative TL was reported. Analysis was intention-to-treat. Findings: Between May 2012 and July 2013, in the overall trial, we randomized 720 geographical clusters of 5551 pregnant women to a control or an intervention arm. In this substudy, after 1 year of intervention, we assessed a total of 662 children (341 intervention and 321 control) and 713 children after 2 years of intervention (383 intervention and 330 control). Children in the intervention arm had significantly shorter relative TL compared with controls after 1 year of intervention (difference -163 base pairs (bp), p=0.001). Between years 1 and 2, TL increased in the intervention arm (+76 bp) and decreased in the controls (-23 bp) (p=0.050). After 2 years, there was no difference between the arms (p=0.305). Interpretation: Our unexpected finding of increased telomere attrition during the first year of life in the intervention group suggests that rapid telomere attrition during this critical period could reflect the improved growth in the intervention group, rather than accumulated stress. Funding: The Bill and Melinda Gates Foundation.


Assuntos
Desinfecção das Mãos , Estado Nutricional , Saneamento , Telômero/metabolismo , Telômero/ultraestrutura , Purificação da Água , Adulto , Bangladesh , Desenvolvimento Infantil , Pré-Escolar , Feminino , Geografia , Humanos , Lactente , Estudos Longitudinais , Masculino , Distribuição Aleatória , População Rural , Adulto Jovem
16.
J Nutr ; 147(11): 2018-2024, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28978678

RESUMO

Background: Leukocyte telomere length (TL) is associated with age-related diseases and early mortality, but there is a lack of data on the determinants of TL in early life. Evidence suggests that dietary intake of marine n-3 (ω-3) polyunsaturated fatty acids (PUFAs) is protective of telomere attrition, yet the effect of methylmercury exposure, also found in fish, on TL is unknown.Objective: The aim of this study was to investigate the associations between prenatal PUFA status, methylmercury exposure, and TL in mothers and children in the SCDS (Seychelles Child Development Study), for whom fish consumption is high.Methods: Blood samples collected from 229 mothers (at 28 wk gestation and delivery) and children (at 5 y of age) in the SCDS first nutrition cohort were analyzed for PUFA concentrations. Prenatal mercury was measured in maternal hair collected at delivery. Postnatal mercury was also measured in children's hair samples with the use of a cumulative metric derived from values obtained at 3-5 y of age. Relative TL was measured in blood obtained from mothers at delivery, in cord blood, and in children at 5 y of age by quantitative polymerase chain reaction. Linear regression models were used to investigate the associations between PUFA status, methylmercury exposure, and TL.Results: Neither prenatal PUFA status or methylmercury exposure was associated with TL of the mother or child or with TL attrition rate. However, a higher prenatal n-6:n-3 PUFA ratio was significantly associated with longer TLs in the mothers (ß = 0.001, P = 0.048). Child PUFA status and methylmercury exposure were not associated with child TL. However, higher family Hollingshead socioeconomic status (SES) scores at 9 mo of age were significantly associated with longer TLs in cord blood (ß = 0.005, P = 0.03).Conclusions: We found no evidence that PUFA status or methylmercury exposure are determinants of TL in either the mother or child. However, our results support the hypothesis that family SES may be associated with child TL.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Ácidos Graxos Insaturados/sangue , Leucócitos/efeitos dos fármacos , Compostos de Metilmercúrio/análise , Telômero/ultraestrutura , Adolescente , Adulto , Animais , Pré-Escolar , Estudos de Coortes , Ácidos Graxos Insaturados/administração & dosagem , Peixes , Contaminação de Alimentos/análise , Cabelo/química , Humanos , Modelos Lineares , Mães , Alimentos Marinhos/análise , Seicheles , Telômero/efeitos dos fármacos , Adulto Jovem
17.
Nucleic Acids Res ; 45(21): 12340-12353, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29040668

RESUMO

AURKB (Aurora Kinase B) is a serine/threonine kinase better known for its role at the mitotic kinetochore during chromosome segregation. Here, we demonstrate that AURKB localizes to the telomeres in mouse embryonic stem cells, where it interacts with the essential telomere protein TERF1. Loss of AURKB function affects TERF1 telomere binding and results in aberrant telomere structure. In vitro kinase experiments successfully identified Serine 404 on TERF1 as a putative AURKB target site. Importantly, in vivo overexpression of S404-TERF1 mutants results in fragile telomere formation. These findings demonstrate that AURKB is an important regulator of telomere structural integrity.


Assuntos
Aurora Quinase B/metabolismo , Telômero/enzimologia , Proteína 1 de Ligação a Repetições Teloméricas/metabolismo , Animais , Aurora Quinase B/fisiologia , Linhagem Celular , Células-Tronco Embrionárias/enzimologia , Humanos , Interfase/genética , Camundongos , Mitose/genética , Mutação , Ligação Proteica , Telômero/ultraestrutura , Proteína 1 de Ligação a Repetições Teloméricas/química , Proteína 1 de Ligação a Repetições Teloméricas/genética
18.
BMC Med Genet ; 18(1): 112, 2017 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-29017469

RESUMO

BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes, and telomere length represents a biological marker for cellular aging. Interpersonal sensitivity, excessive sensitivity to the behavior and feelings of others, is one of the vulnerable factors to depression. In the present study, we examined the effect of interpersonal sensitivity on telomere length in healthy subjects. METHODS: The subjects were 159 unrelated healthy Japanese volunteers. Mean age ± SD (range) of the subjects was 42.3 ± 7.8 (30-61) years. Interpersonal sensitivity was assessed by the Japanese version of the Interpersonal Sensitivity Measure (IPSM). Leukocyte telomere length was determined by a quantitative real-time PCR method. RESULTS: Higher scores of the total IPSM were significantly (ß = -0.163, p = 0.038) related to shorter telomere length. In the sub-scale analysis, higher scores of timidity were significantly (ß = -0.220, p = 0.044) associated with shorter telomere length. CONCLUSIONS: The present study suggests that subjects with higher interpersonal sensitivity have shorter leukocyte telomere length, implying that interpersonal sensitivity has an impact on cellular aging.


Assuntos
Leucócitos/citologia , Personalidade/genética , Telômero/ultraestrutura , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Senescência Celular/genética , Estudos Transversais , Depressão/genética , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Análise de Sequência de DNA , Homeostase do Telômero
19.
Proc Biol Sci ; 284(1862)2017 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-28878065

RESUMO

Urban environments pose novel challenges, as well as opportunities, for urban-dwelling wildlife. Although differences have been reported in several phenotypic traits (e.g. morphology, physiology and behaviour) between urban and rural populations, it is poorly understood whether this affects individual fitness. Telomere dynamics are posited as one possible mechanism underlying senescence and mortality. It was recently shown that telomere shortening is accelerated when growing up in an urban, compared with a rural, environment. However, the implications of accelerated telomere attrition for fitness are still unclear. Here, we examine the relationship between telomere length (TL) and survival in a bird common to urban and rural environments, and during both early and later life. The results reveal that TL is a strong predictor of post-fledging survival and recruitment in both habitats but, crucially, selective disappearance of individuals with short telomeres early in life is more pronounced in the urban environment, resulting in a longer average TL among the adult population. However, following recruitment, we found no difference in the relationship between TL and survival between the urban and rural environments. This indicates that the urban environment has negative effects in early life, while during later life the benefits could potentially outweigh the costs.


Assuntos
Aptidão Genética , Passeriformes/genética , Encurtamento do Telômero , Telômero/ultraestrutura , Animais , Cidades , Meio Ambiente
20.
Proc Biol Sci ; 284(1861)2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28855370

RESUMO

Early-life adversity can affect health, survival and fitness later in life, and recent evidence suggests that telomere attrition may link early conditions with their delayed consequences. Here, we investigate the link between early-life competition and telomere length in wild meerkats. Our results show that, when multiple females breed concurrently, increases in the number of pups in the group are associated with shorter telomeres in pups. Given that pups from different litters compete for access to milk, we tested whether this effect is due to nutritional constraints on maternal milk production, by experimentally supplementing females' diets during gestation and lactation. While control pups facing high competition had shorter telomeres, the negative effects of pup number on telomere lengths were absent when maternal nutrition was experimentally improved. Shortened pup telomeres were associated with reduced survival to adulthood, suggesting that early-life competition for nutrition has detrimental fitness consequences that are reflected in telomere lengths. Dominant females commonly kill pups born to subordinates, thereby reducing competition and increasing growth rates of their own pups. Our work suggests that an additional benefit of infanticide may be that it also reduces telomere shortening caused by competition for resources, with associated benefits for offspring ageing profiles and longevity.


Assuntos
Envelhecimento , Herpestidae/genética , Longevidade , Encurtamento do Telômero , Telômero/ultraestrutura , Animais , Feminino , Aptidão Genética
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