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1.
Nat Commun ; 12(1): 1626, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712616

RESUMO

Minichromosome maintenance protein 10 (MCM10) is essential for eukaryotic DNA replication. Here, we describe compound heterozygous MCM10 variants in patients with distinctive, but overlapping, clinical phenotypes: natural killer (NK) cell deficiency (NKD) and restrictive cardiomyopathy (RCM) with hypoplasia of the spleen and thymus. To understand the mechanism of MCM10-associated disease, we modeled these variants in human cell lines. MCM10 deficiency causes chronic replication stress that reduces cell viability due to increased genomic instability and telomere erosion. Our data suggest that loss of MCM10 function constrains telomerase activity by accumulating abnormal replication fork structures enriched with single-stranded DNA. Terminally-arrested replication forks in MCM10-deficient cells require endonucleolytic processing by MUS81, as MCM10:MUS81 double mutants display decreased viability and accelerated telomere shortening. We propose that these bi-allelic variants in MCM10 predispose specific cardiac and immune cell lineages to prematurely arrest during differentiation, causing the clinical phenotypes observed in both NKD and RCM patients.


Assuntos
Alelos , Cardiomiopatias/genética , Proteínas de Manutenção de Minicromossomo/genética , Proteínas de Manutenção de Minicromossomo/imunologia , Encurtamento do Telômero , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Replicação do DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Endonucleases/genética , Endonucleases/metabolismo , Humanos , Células Matadoras Naturais
2.
Ecotoxicol Environ Saf ; 213: 112037, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33609998

RESUMO

OBJECTIVE: Telomere length (TL) is a biomarker for biological aging, and the initial setting of TL at birth is a determinant factor of TL in later life. Newborn TL is sensitive to maternal metals concentrations, while study about the association between maternal manganese (Mn) concentrations and newborn TL was not found. Our study aimed to investigate whether newborn TL is related to maternal Mn concentrations. METHODS: Data were collected from a birth cohort study of 762 mother-newborn pairs conducted from November 2013 to March 2015 in Wuhan, China. We measured the Mn concentrations in spot urine samples collected during three trimesters by inductively coupled plasma mass spectrometry (ICP-MS) and relative cord blood TL by quantitative real-time polymerase chain reaction (qPCR). We applied multiple informant models to investigate the associations between maternal Mn concentrations and cord blood TL. RESULTS: The geometric mean of creatinine-corrected urinary Mn concentrations were 1.58 µg/g creatinine, 2.53 µg/g creatinine, and 2.62 µg/g creatinine in the first, second, and third trimester, respectively. After adjusting for potential confounders, a doubling of maternal urinary Mn concentration during the second trimester was related to a 2.10% (95% CI: 0.25%, 3.99%) increase in cord blood TL. Mothers with the highest tertile of urinary Mn concentrations during the second trimester had a 9.67% (95% CI: 2.13%, 17.78%) longer cord blood TL than those with the lowest tertile. This association was more evident in male infants. No relationship was found between maternal urinary Mn concentrations and cord blood TL during the first and third trimesters in our study. CONCLUSIONS: Our findings suggested that maternal Mn concentration during the second trimester was positively associated with newborn TL. These results might provide an epidemiology evidence on the protective role of maternal Mn for newborn TL and offer clues for the early prevention of telomere shortening related diseases.


Assuntos
Poluentes Ambientais/urina , Manganês/urina , Telômero/efeitos dos fármacos , Adulto , Envelhecimento , China , Estudos de Coortes , Feminino , Sangue Fetal/química , Humanos , Lactente , Recém-Nascido , Masculino , Manganês/análise , Exposição Materna/estatística & dados numéricos , Gravidez , Trimestres da Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Encurtamento do Telômero
3.
Int J Mol Sci ; 22(2)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33435578

RESUMO

Cells can become senescent in response to stress. Senescence is a process characterised by a stable proliferative arrest. Sometimes it can be beneficial-for example, it can suppress tumour development or take part in tissue repair. On the other hand, studies show that it is also involved in the ageing process. DNA damage response (DDR) is triggered by DNA damage or telomere shortening during cell division. When left unresolved, it may lead to the activation of senescence. Senescent cells secrete certain proteins in larger quantities. This phenomenon is referred to as senescence-associated secretory phenotype (SASP). SASP can induce senescence in other cells; evidence suggests that overabundance of senescent cells contributes to ageing. SASP proteins include proinflammatory cytokines and metalloproteinases, which degrade the extracellular matrix. Shortening of telomeres is another feature associated with organismal ageing. Older organisms have shorter telomeres. Restoring telomerase activity in mice not only slowed but also partially reversed the symptoms of ageing. Changes in chromatin structure during senescence include heterochromatin formation or decondensation and loss of H1 histones. During organismal ageing, cells can experience heterochromatin loss, DNA demethylation and global histone loss. Cellular and organismal ageing are both complex processes with many aspects that are often related. The purpose of this review is to bring some of these aspects forward and provide details regarding them.


Assuntos
Envelhecimento/genética , Senescência Celular/genética , Cromatina/genética , Dano ao DNA , Inflamação/genética , Telômero/genética , Animais , Cromatina/metabolismo , Heterocromatina/genética , Heterocromatina/metabolismo , Humanos , Inflamação/metabolismo , Telômero/metabolismo , Encurtamento do Telômero/genética
4.
Int J Mol Sci ; 22(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466545

RESUMO

Involvement of epigenetic mechanisms in the regulation of telomeres and transposable elements (TEs), genomic regions with the protective and potentially detrimental function, respectively, has been frequently studied. Here, we analyzed telomere lengths in Arabidopsis thaliana plants of Columbia, Landsberg erecta and Wassilevskija ecotypes exposed repeatedly to the hypomethylation drug zebularine during germination. Shorter telomeres were detected in plants growing from seedlings germinated in the presence of zebularine with a progression in telomeric phenotype across generations, relatively high inter-individual variability, and diverse responses among ecotypes. Interestingly, the extent of telomere shortening in zebularine Columbia and Wassilevskija plants corresponded to the transcriptional activation of TEs, suggesting a correlated response of these genomic elements to the zebularine treatment. Changes in lengths of telomeres and levels of TE transcripts in leaves were not always correlated with a hypomethylation of cytosines located in these regions, indicating a cytosine methylation-independent level of their regulation. These observations, including differences among ecotypes together with distinct dynamics of the reversal of the disruption of telomere homeostasis and TEs transcriptional activation, reflect a complex involvement of epigenetic processes in the regulation of crucial genomic regions. Our results further demonstrate the ability of plant cells to cope with these changes without a critical loss of the genome stability.


Assuntos
Arabidopsis/genética , Citidina/análogos & derivados , Elementos de DNA Transponíveis/genética , Telômero/genética , Arabidopsis/metabolismo , Citidina/genética , Citosina/metabolismo , Metilação de DNA/genética , Epigênese Genética/genética , Células Vegetais/metabolismo , Homeostase do Telômero/genética , Encurtamento do Telômero/genética , Ativação Transcricional/genética
5.
Environ Toxicol Pharmacol ; 83: 103575, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33385577

RESUMO

Telomeres are "protective messengers" at the ends of eukaryotic chromosomes that protect them from degradation, end to end fusion and recombination. Admittedly, telomeres progressively shorten with age that can also be significantly accelerated by pathological conditions, which are often considered as potential contributors for cellular senescence. It is commonly believed that constant accumulation of senescent cells may lead to dysfunctional tissues and organs, thereby accelerating aging process and subsequent occurrence of age-related diseases. In particular, epidemiological data has indicated a significant association between environmental pollutants exposure and a high incidence of age-related diseases. Moreover, there is growing evidence that environmental toxicity has a detrimental impact on telomere length. Overall, a consensus is emerging that environmental pollutants exposure could lead to accelerated telomere erosion and further induce premature senescence, which may be responsible for the acceleration of aging and the high morbidity and mortality rates of age-related diseases.


Assuntos
Envelhecimento , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Telômero/efeitos dos fármacos , Animais , Humanos , Encurtamento do Telômero/efeitos dos fármacos
6.
Aging (Albany NY) ; 13(1): 1-15, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33428591

RESUMO

The incidence of severe manifestations of COVID-19 increases with age with older patients showing the highest mortality, suggesting that molecular pathways underlying aging contribute to the severity of COVID-19. One mechanism of aging is the progressive shortening of telomeres, which are protective structures at chromosome ends. Critically short telomeres impair the regenerative capacity of tissues and trigger loss of tissue homeostasis and disease. The SARS-CoV-2 virus infects many different cell types, forcing cell turn-over and regeneration to maintain tissue homeostasis. We hypothesize that presence of short telomeres in older patients limits the tissue response to SARS-CoV-2 infection. We measure telomere length in peripheral blood lymphocytes COVID-19 patients with ages between 29 and 85 years-old. We find that shorter telomeres are associated to increased severity of the disease. Individuals within the lower percentiles of telomere length and higher percentiles of short telomeres have higher risk of developing severe COVID-19 pathologies.


Assuntos
Envelhecimento/genética , Encurtamento do Telômero , Telômero/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , /tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença
7.
Nat Commun ; 12(1): 512, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479235

RESUMO

To achieve replicative immortality, cancer cells must activate telomere maintenance mechanisms to prevent telomere shortening. ~85% of cancers circumvent telomeric attrition by re-expressing telomerase, while the remaining ~15% of cancers induce alternative lengthening of telomeres (ALT), which relies on break-induced replication (BIR) and telomere recombination. Although ALT tumours were first reported over 20 years ago, the mechanism of ALT induction remains unclear and no study to date has described a cell-based model that permits the induction of ALT. Here, we demonstrate that infection with Kaposi's sarcoma herpesvirus (KSHV) induces sustained acquisition of ALT-like features in previously non-ALT cell lines. KSHV-infected cells acquire hallmarks of ALT activity that are also observed in KSHV-associated tumour biopsies. Down-regulating BIR impairs KSHV latency, suggesting that KSHV co-opts ALT for viral functionality. This study uncovers KSHV infection as a means to study telomere maintenance by ALT and reveals features of ALT in KSHV-associated tumours.


Assuntos
Neoplasias/genética , Homeostase do Telômero/genética , Encurtamento do Telômero/genética , Telômero/genética , Carcinogênese , Linhagem Celular , Linhagem Celular Tumoral , Dano ao DNA , Replicação do DNA/genética , Células HeLa , Herpesvirus Humano 8/fisiologia , Interações Hospedeiro-Patógeno , Humanos , Hibridização in Situ Fluorescente , Neoplasias/patologia , Neoplasias/virologia , Proteoma/genética , Proteoma/metabolismo , Telomerase/genética , Telomerase/metabolismo
8.
Arterioscler Thromb Vasc Biol ; 41(3): 1047-1061, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33504179

RESUMO

Shortened telomeres have been linked to numerous chronic diseases, most importantly coronary artery disease, but the underlying mechanisms remain ill defined. Loss-of-function mutations and deletions in telomerase both accelerate telomere shortening but do not necessarily lead to a clinical phenotype associated with atherosclerosis, questioning the causal role of telomere length in cardiac pathology. The differential extranuclear functions of the 2 main components of telomerase, telomerase reverse transcriptase and telomerase RNA component, offer important clues about the complex relationship between telomere length and cardiovascular pathology. In this review, we critically discuss relevant preclinical models, genetic disorders, and clinical studies to elucidate the impact of telomerase in cardiovascular disease and its potential role as a therapeutic target. We suggest that the antioxidative function of mitochondrial telomerase reverse transcriptase might be atheroprotective, making it a potential target for clinical trials. Graphic Abstract: A graphic abstract is available for this article.


Assuntos
Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/terapia , Telomerase/metabolismo , Animais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Ensaios Clínicos como Assunto , Medicamentos de Ervas Chinesas/uso terapêutico , Exercício Físico , Estudo de Associação Genômica Ampla , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Leucócitos/enzimologia , Camundongos , Modelos Cardiovasculares , Mutação , RNA/genética , Telomerase/sangue , Telomerase/genética , Homeostase do Telômero/fisiologia , Encurtamento do Telômero/fisiologia
9.
Gene ; 766: 145127, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32937184

RESUMO

Telomeres are duplex tandem repeats of DNA sequence 5'-TTAGGG-3' at chromosomal ends synthesized by telomerase enzyme (TE). Telomeres length (TL) shortening is associated with age and age-related disorders. Recently, we demonstrated marked leukocytes TL (LTL) shortening in T2DM. To set the relationship between the TE, LTL and T2DM, we analyzed samples from 212 Kuwaiti subjects, 112 patients withT2DM and 100 non-diabetic subjects. The plasma TE and fasting insulin were measured by ELISA, the LTL was estimated by qPCR and three SNPs of genes related to TL; TERC rs12696304 (C/G), TERT rs2736100 (C/A) and ACYP2 rs6713088 (C/G) were genotyped by rtPCR. Results revealed comparable TE levels and alleles/genotypes between the cases and controls with no influence of either on the LTL. Interestingly, although the plasma concentration of the TE was generally low, it was significantly influenced by the TERT and ACYP2 but not TERC polymorphisms. The CC genotype carriers of rs2736100 (C/A) had significantly higher plasma TE levels compared to CA and AA carriers, p 0.009 and p 0.047, respectively, and the A-allele was associated with low TE, p 0.018. Similarly, significantly higher TE levels were detected in CC carriers of ACYP2 rs6713088 (C/G) compared with GC carriers, p 0.002, and the G-allele was associated with low TE, p 0.009. Finally, the TERT and ACYP2 polymorphisms had an influence on blood glucose levels. In conclusion, the telomeres shortening in T2DM was not due to TE deficiency or gene polymorphisms, while the TE levels were significantly associated with the TERT and ACYP2 but not TERC polymorphisms.


Assuntos
Hidrolases Anidrido Ácido/genética , Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleotídeo Único/genética , RNA/genética , Telomerase/genética , Encurtamento do Telômero/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Telomerase/sangue
10.
High Blood Press Cardiovasc Prev ; 28(1): 49-55, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33315189

RESUMO

INTRODUCTION: Cellular senescence and fibrosis are important phenomena in the development of heart failure (HF). These processes are closely related to telomeric length (TL). AIM: To assess cellular senescence in HF through the study of TL in peripheral blood mononuclear cells (PBMCs). METHODS: Using real-time PCR, TL was measured in PBMCs from 20 patients diagnosed with HF, aged between 51 and 77 years (50% males). Ten patients had HF with reduced ejection fraction (HFrEF) and ten had preserved EF (HFpEF). TL was measured in 20 healthy controls matched by age and gender. Obtained values were compared with an internal control, the 36B4 gene, which never modifies its expression, and correlated with the clinical parameters. RESULTS: TL mean was 1327 in patients with HF (95% CI 1309-1344) compared to 1286 (95% CI 1264-1308) in controls (p = 0.005). No differences were found when studying the correlation of telomere size with subgroups by gender, left ventricle ejection fraction (LVEF), presence of ischemic heart disease, smoking, Chronic Obstructive Pulmonary Disease (COPD), NYHA stage, degree of renal function or number of hospital admissions in the previous year. A significant and negative correlation was found between age and renal function (r = - 0.544, p < 0.05), as well as LVEF and NT-proBNP values (ρ = - 0.475, p < 0.05). CONCLUSIONS: TL is shorter in patients with HF when compared with age and gender balanced controls. The shortening of TL is independent of age, gender and degree of kidney function, and does not correlate with LVEF decrease or functional status.


Assuntos
Insuficiência Cardíaca/metabolismo , Encurtamento do Telômero , Telômero/metabolismo , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Função Ventricular Esquerda
11.
Int J Mol Sci ; 21(24)2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33353140

RESUMO

Telomere length (TL) influences the development of lifestyle-related diseases, and neonatal TL may influence their prevalence. Various factors have been reported to affect neonatal TL. Although the fetus is exposed to multiple conditions in utero, the main factors affecting the shortening of neonatal TL are still not known. In this study, we sought to identify factors that influence fetal TL. A total of 578 mother-newborn pairs were included for TL analysis. TL was measured in genomic DNA extracted from cord blood samples using quantitative PCR. The clinical factors examined at enrollment included the following intrauterine environmental factors: maternal age, assisted reproductive technology (ART) used, body mass index (BMI), gestational diabetes mellitus (GDM), maternal stress, smoking, alcohol consumption, preterm delivery, small-for-gestational-age, neonatal sex, and placental weight. Univariate and multivariate regression analyses were used to verify the relationship between neonatal TL and these clinical factors. The median neonatal TL to single-copy gene ratio was 1.0. Pregnancy with ART was among the 11 factors associated with shorter neonatal TL. From multiple regression analysis, we determined that neonatal TL was significantly shorter for pregnancies in the ART group than in the other groups. We conclude that pregnancy with ART is associated with shorter neonatal TL.


Assuntos
Idade Gestacional , Idade Materna , Técnicas de Reprodução Assistida/estatística & dados numéricos , Encurtamento do Telômero/genética , Adolescente , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Adulto Jovem
12.
Oecologia ; 194(4): 609-620, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33201323

RESUMO

Telomere shortening has been used as an indicator of aging and is believed to accelerate under harsh environmental conditions. This can be attributed to the fact that telomere shortening has often been regarded as non-reversible and negatively impacting fitness. However, studies of laboratory mice indicate that they may be able to repair telomere loss to recover from environmental harshness, as indicated by recent studies in hibernating rodents. We studied seasonal variation in telomere dynamics in African striped mice (Rhabdomys pumilio) living in a highly seasonal environment. In our annual species, individuals born in the moist spring (high food availability) need to survive the harsh dry summer (low food availability) to be able to reproduce in the following spring. We studied the effect of the harsh dry vs. the benign moist season on telomere dynamics. We also tested if telomere length or the rate of change in telomere length over the dry season predicted the probablity of dissapearance from the population at the same time. Male, but not female, stripped mice showed age-related telomere erosion. Telomeres were longer at the beginning of the dry season compared to the rest of the year. Telomeres increased significantly in length during the moist season. Neither telomere length at the onset of the dry season nor telomere loss over the dry season predicted whether or not individuals disappeared. In conclusion, our data suggest that seasonal attrition and restoring of telomeres also occurs in non-hibernating wild rodents living in hot food restricted environments.


Assuntos
Murinae , Telômero , Envelhecimento , Animais , Alimentos , Humanos , Masculino , Camundongos , Murinae/genética , Estações do Ano , Encurtamento do Telômero
13.
Rev. habanera cienc. méd ; 19(5): e3144, sept.-oct. 2020.
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1144682

RESUMO

RESUMEN 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)


ABSTRACT 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)


Assuntos
Humanos , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Encurtamento do Telômero/genética
15.
Science ; 369(6509)2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32913074

RESUMO

Telomere shortening is a hallmark of aging. Telomere length (TL) in blood cells has been studied extensively as a biomarker of human aging and disease; however, little is known regarding variability in TL in nonblood, disease-relevant tissue types. Here, we characterize variability in TLs from 6391 tissue samples, representing >20 tissue types and 952 individuals from the Genotype-Tissue Expression (GTEx) project. We describe differences across tissue types, positive correlation among tissue types, and associations with age and ancestry. We show that genetic variation affects TL in multiple tissue types and that TL may mediate the effect of age on gene expression. Our results provide the foundational knowledge regarding TL in healthy tissues that is needed to interpret epidemiological studies of TL and human health.


Assuntos
Envelhecimento/genética , Homeostase do Telômero/genética , Encurtamento do Telômero/genética , Telômero/fisiologia , Marcadores Genéticos , Variação Genética , Humanos , Especificidade de Órgãos
16.
Mol Ecol ; 29(16): 2951-2953, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32745307

RESUMO

The relationship of telomere shortening and cellular ageing in cultured cells such as fibroblasts is straightforward: telomeres shorten with an increasing number of cell divisions until they trigger replicative senescence which prevents further mitotic cycles. But studies investigating the relationship between telomere shortening and ageing in whole organisms show contrasting results: while there is a clear decline in telomere length (TL) with chronological age in some species such as humans, no such decline is observed in others. In this issue of Molecular Ecology, Foley et al. (2020) show that experiencing harsh weather conditions correlates with longitudinal telomere shortening in the bat species Myotis myotis, whereas chronological age does not (Foley et al., 2020). Further, the authors investigated whether genetics influence TL and find a low heritability (h2  = 0.01-0.06) again suggesting that environmental effects are the dominant drivers of variation in TL in this species. These are important findings as there is disagreement in the literature about the relative magnitude of genetic and environmental effects contributing to TL variation in different species. This paper investigating the impact of environmental effects makes a novel and important contribution to the literature on TL in free-living mammals.


Assuntos
Quirópteros , Encurtamento do Telômero , Animais , Senescência Celular , Quirópteros/genética , Humanos , Telômero/genética , Tempo (Meteorologia)
17.
Life Sci ; 259: 118341, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32853653

RESUMO

Aging is a form of a gradual loss of physiological integrity that results in impaired cellular function and ultimately increased vulnerability to disease and death. This process is a significant risk factor for critical age-related disorders such as cancer, diabetes, cardiovascular disease, and neurological conditions. Several mechanisms contribute to aging, most notably progressive telomeres shortening, which can be counteracted by telomerase enzyme activity and increasing in this enzyme activity associated with partly delaying the onset of aging. Individual behaviors and environmental factors such as nutrition affect the life-span by impact the telomerase activity rate. Healthy eating habits, including antioxidant intakes, such as polyphenols, can have a positive effect on telomere length by this mechanism. In this review, after studying the underlying mechanisms of aging and understanding the relationships between telomeres, telomerase, and aging, it has been attempted to explain the effect of polyphenols on reversing the oxidative stress and aging process.


Assuntos
Antioxidantes/farmacologia , Plantago/efeitos dos fármacos , Polifenóis/farmacologia , Telômero/efeitos dos fármacos , Animais , Combinação de Medicamentos , Humanos , Extrato de Senna , Encurtamento do Telômero/efeitos dos fármacos
18.
Proc Biol Sci ; 287(1933): 20201378, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32842933

RESUMO

Prenatal effects on telomere length are increasingly recognized as a potential contributor to the developmental origin of health and adult disease. While it is becoming clear that telomere length is influenced by prenatal conditions, the factors affecting telomere dynamics during embryogenesis remain poorly understood. We manipulated both the pace and stability of embryonic development through varying incubation temperature and its stability in Japanese quail. We investigated the impact on telomere dynamics from embryogenesis to adulthood, together with three potential drivers of telomere shortening, growth rate, oxidative damage and prenatal glucocorticoid levels. Telomere length was not affected by our prenatal manipulation for the first 75% of embryogenesis, but was reduced at hatching in groups experiencing faster (i.e. high temperature) or less stable embryonic development. These early life differences in telomere length persisted until adulthood. The effect of developmental instability on telomere length at hatching was potentially mediated by an increased secretion of glucocorticoid hormones during development. Both the pace and the stability of embryo development appear to be key factors determining telomere length and dynamics into adulthood, with fast and less stable development leading to shorter telomeres, with the potential for adverse associated outcomes in terms of reduced longevity.


Assuntos
Coturnix , Desenvolvimento Embrionário , Telômero , Adulto , Animais , Feminino , Glucocorticoides , Humanos , Gravidez , Encurtamento do Telômero , Temperatura
19.
Artigo em Inglês | MEDLINE | ID: mdl-32604805

RESUMO

Telomere length in early life has been recently associated with biological aging and development of negative consequences in later adult life. A relevant area of research has emerged to understand the factors that impact telomere length in children. We conducted a bibliometric analysis to track research output and identify global trends and gaps in the knowledge of telomere length in children. Bibliographic data were retrieved from the Web of Science database and then analyzed by using Bibliometrix R package. A total of 840 publications were yielded from 1991 to 2019. The references were prominently published in journals, with 20 high ranked journals contributing to 30% of literature on telomere length in children. The USA was the most productive country (35.7%), followed by Europe (12.1%), and Asia (11.9%). A knowledge map of telomere length in children through keyword analyses revealed that there were two potential main lines of research based on two different approaches: genomic research and epidemiological research. This study shows that telomere length in children is a topic of research that has gained significant relevance in the last decade. This bibliometric study may be helpful in identifying research trends and finding research hot spots and gaps in this research field.


Assuntos
Bibliometria , Homeostase do Telômero , Encurtamento do Telômero , Telômero , Ásia , Criança , Europa (Continente) , Humanos , Publicações , Estados Unidos
20.
Nat Commun ; 11(1): 3321, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620872

RESUMO

Human telomeres are bound by the telomere repeat binding proteins TRF1 and TRF2. Telomere shortening in human cells leads to a DNA damage response that signals replicative senescence. While insufficient loading of TRF2 at shortened telomeres contributes to the DNA damage response in senescence, the contribution of TRF1 to senescence induction has not been determined. Here we show that counter to TRF2 deficiency-mediated induction of DNA damage, TRF1 deficiency serves a protective role to limit induction of DNA damage induced by subtelomere recombination. Shortened telomeres recruit insufficient TRF1 and as a consequence inadequate tankyrase 1 to resolve sister telomere cohesion. Our findings suggest that the persistent cohesion protects short telomeres from inappropriate recombination. Ultimately, in the final division, telomeres are no longer able to maintain cohesion and subtelomere copying ensues. Thus, the gradual loss of TRF1 and concomitant persistent cohesion that occurs with telomere shortening ensures a measured approach to replicative senescence.


Assuntos
Encurtamento do Telômero/genética , Telômero/genética , Proteína 1 de Ligação a Repetições Teloméricas/genética , Proteína 2 de Ligação a Repetições Teloméricas/genética , Sequência de Bases , Linhagem Celular , Linhagem Celular Tumoral , Senescência Celular/genética , Dano ao DNA , Células HEK293 , Heterocromatina/genética , Heterocromatina/metabolismo , Humanos , Hibridização in Situ Fluorescente , Mutação , Interferência de RNA , Tanquirases/metabolismo , Telômero/metabolismo , Proteína 1 de Ligação a Repetições Teloméricas/deficiência , Proteína 1 de Ligação a Repetições Teloméricas/metabolismo , Proteína 2 de Ligação a Repetições Teloméricas/deficiência , Proteína 2 de Ligação a Repetições Teloméricas/metabolismo
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