RESUMEN
Background: Polycystic Ovary Syndrome (PCOS) often present metabolic disorders and hyperandrogenism (HA), facts that may influence the telomere length (TL). Aims: To compare the absolute TL (aTL) between women with PCOS and control women, and their association with the presence of obesity and HA parameters. Materials and methods: The PCOS group included 170 unrelated women outpatients and the control group, 64 unrelated donor women. Anthropometric, biochemical-clinical parameters and androgen profile were determined. The PCOS patients were divided accordingly to the presence of obesity and androgenic condition. The aTL was determined from peripheral blood leukocytes by Real Time quantitative PCR. Results: Women with PCOS exhibited a significantly longer aTL than controls after age adjustment (p=0.001). A stepwise multivariate linear regression in PCOS women, showed that WC (waist circumference) contributed negatively (b=-0.17) while testosterone levels contributed positively (b=7.24) to aTL. The non-Obese PCOS (noOB-PCOS) presented the longest aTL when compared to controls (p=0.001). Meanwhile, the aTL was significantly higher in the hyperandrogenic PCOS phenotype (HA-PCOS) than in the controls (p=0.001) and non hyperandrogenic PCOS phenotype (NHA-PCOS) (p=0.04). Interestingly, when considering obesity and HA parameters in PCOS, HA exerts the major effect over the aTL as non-obese HA exhibited the lengthiest aTL (23.9 ± 13.13 Kbp). Conversely, the obese NHA patients showed the shortest aTL (16.5 ± 10.59 Kbp). Conclusions: Whilst a shorter aTL could be related to the presence of obesity, a longer aTL would be associated with HA phenotype. These findings suggest a balance between the effect produced by the different metabolic and hormonal components, in PCOS women.
Asunto(s)
Hiperandrogenismo/genética , Obesidad/genética , Síndrome del Ovario Poliquístico/genética , Telómero/metabolismo , Adulto , Argentina/epidemiología , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Humanos , Hiperandrogenismo/complicaciones , Hiperandrogenismo/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/epidemiología , Estudios Retrospectivos , Telómero/química , Homeostasis del Telómero/fisiología , Testosterona/sangreRESUMEN
Chronic stress is related to the acceleration of telomere shortening. Recent work showed a correlation between chronic psychosocial stress and reduced telomere length in certain cells. The exposure of T lymphocytes to cortisol promoted a significant reduction in telomerase activity. Although stress can promote changes in telomere length, whether increased glucocorticoid concentrations alter telomere length in brain tissue cells is unclear. In addition to modulating the activity of the stress system, estrogen also influences telomere length. The objective of this study was to verify whether chronic exposure to glucocorticoids promotes changes in the telomere length of encephalic areas involved in the control of HPA axis activity and whether estrogen affects these changes. Wistar rats were ovariectomized and treated with estradiol cypionate [(50 or 100 µg/kg, subcutaneously)] or oil and 20 mg/kg corticosterone or vehicle (isotonic saline with 2% Tween 80, subcutaneously) for 28 days. On the day after the end of the hormonal treatment, the animals were euthanized for collection of blood, brain and pituitary gland samples. Estrogen modulated the activity of the HPA axis. CRH, AVP and POMC mRNA levels were reduced by estrogen. At least in doses and treatment time used, there was no correlation between effects of exposure to glucocorticoids and estrogen on telomere length in the brain areas of female rats. However, estrogen treatment reduced the telomere length in the central amygdala and dorsal hippocampus, but not in the PVN, indicating a variation of reaction of telomeres for estrogen in different brain areas.
Asunto(s)
Corticosterona/farmacología , Estrógenos/farmacología , Homeostasis del Telómero/fisiología , Hormona Adrenocorticotrópica/metabolismo , Amígdala del Cerebelo/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Corticosterona/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Estrógenos/metabolismo , Femenino , Hipocampo/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/metabolismo , Ratas , Estrés Fisiológico , Telómero/efectos de los fármacos , Telómero/metabolismo , Telómero/fisiología , Homeostasis del Telómero/efectos de los fármacosRESUMEN
OBJECTIVE: To test the association between early puberty and telomere length in preadolescent girls and mothers from a large representative sample of US females. STUDY DESIGN: We analyzed data from 1194 preadolescent girls and 2421 mothers from the Fragile Families and Child Wellbeing Study. Participants were from a population-based birth cohort (1998-2000) born in large US cities. Telomere length was assessed by quantitative polymerase chain reaction from saliva samples provided by preadolescent girls and mothers of preadolescent youth. Mothers completed a questionnaire about their child's pubertal development to determine concurrent Tanner stages and provided self-reports of her own age at menarche. Linear regression models were used to estimate the association between pubertal development (status and timing) and telomere length. RESULTS: Early pubertal timing but not pubertal status was associated with shorter telomere length in preadolescent girls (P < .01). Early age at menarche was associated with shorter telomere length in a sample of mothers of preadolescent youth (P < .05). CONCLUSIONS: Results provide evidence for the association between early puberty and shorter telomeres evidenced by associations in both preadolescent girls and mothers. Future research should address the limitations of this study by using longitudinal measurements of pubertal development assessed through medical examinations and repeated assessments of telomere length to capture telomere attrition.
Asunto(s)
Desarrollo Infantil , Menarquia/genética , Madres , Pubertad/genética , Homeostasis del Telómero/fisiología , Telómero/genética , Adolescente , Niño , Femenino , Humanos , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: The uterine environment may influence telomere length at birth, which is essential for cellular function, aging, and disease susceptibility over the lifespan. However, little is known about the impact of toxic chemicals on early-life telomeres. Therefore, we assessed the potential impact of multiple toxic metals on relative telomere length (rTL) in the maternal blood, cord blood, and placenta, as well as the potential modifying effects of pro-oxidants. METHOD: In a mother-child cohort in northern Argentina (n = 169), we measured multiple toxic metals in the maternal blood or urine collected during late pregnancy, as well as the placenta and cord blood collected at delivery, using inductively coupled plasma mass spectrometry (ICP-MS). We assessed associations of log2-transformed metal concentrations with rTL, measured in maternal and cord blood leukocytes and the placenta by real-time PCR, using multivariable-adjusted linear regression. Additionally, we tested for modifications by antioxidants (zinc, selenium, folate, and vitamin D3). RESULTS: Exposure to boron and antimony during pregnancy was associated with shorter maternal rTL, and lithium with longer maternal rTL; a doubling of exposure was associated with changes corresponding to 0.2-0.4 standard deviations (SD) of the rTL. Arsenic concentrations in the placenta (n = 98), blood, and urine were positively associated with placental rTL, about 0.2 SD by doubled arsenic. In the cord blood (n = 88), only lead was associated with rTL (inversely), particularly in boys (p for interaction 0.09). Stratifying by newborn sex showed ten times stronger association in boys (about 0.6 SD) than in girls. The studied antioxidants did not modify the associations, except that with antimony. CONCLUSIONS: Elevated exposure to boron, lithium, arsenic, and antimony was associated with maternal or newborn rTL in a tissue-specific, for lead also sex-specific, manner. Nutritional antioxidants did not generally influence the associations.
Asunto(s)
Antioxidantes/administración & dosificación , Exposición a Riesgos Ambientales/análisis , Exposición Materna , Fenómenos Fisiologicos Nutricionales Maternos , Metales Pesados/toxicidad , Homeostasis del Telómero/fisiología , Telómero/fisiología , Adolescente , Adulto , Argentina/epidemiología , Niño , Estudios de Cohortes , Dieta , Exposición a Riesgos Ambientales/prevención & control , Femenino , Sangre Fetal/efectos de los fármacos , Sangre Fetal/metabolismo , Humanos , Recién Nacido , Masculino , Exposición Materna/estadística & datos numéricos , Fenómenos Fisiologicos Nutricionales Maternos/efectos de los fármacos , Intercambio Materno-Fetal/efectos de los fármacos , Intercambio Materno-Fetal/genética , Metales Pesados/análisis , Metales Pesados/sangre , Metales Pesados/orina , Madres , Placenta/efectos de los fármacos , Placenta/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/genética , Efectos Tardíos de la Exposición Prenatal/prevención & control , Telómero/efectos de los fármacos , Homeostasis del Telómero/efectos de los fármacos , Adulto JovenRESUMEN
Replication protein A (RPA), the major eukaryotic single-stranded binding protein, is a heterotrimeric complex formed by RPA-1, RPA-2, and RPA-3. RPA is a fundamental player in replication, repair, recombination, and checkpoint signaling. In addition, increasing evidences have been adding functions to RPA in telomere maintenance, such as interaction with telomerase to facilitate its activity and also involvement in telomere capping in some conditions. Trypanosoma cruzi, the etiological agent of Chagas disease is a protozoa parasite that appears early in the evolution of eukaryotes. Recently, we have showed that T. cruziRPA presents canonical functions being involved with DNA replication and DNA damage response. Here, we found by FISH/IF assays that T. cruziRPA localizes at telomeres even outside replication (S) phase. In vitro analysis showed that one telomeric repeat is sufficient to bind RPA-1. Telomeric DNA induces different secondary structural modifications on RPA-1 in comparison with other types of DNA. In addition, RPA-1 presents a higher affinity for telomeric sequence compared to randomic sequence, suggesting that RPA may play specific roles in T. cruzi telomeric region.
Asunto(s)
Proteína de Replicación A/metabolismo , Telomerasa/metabolismo , Telómero/metabolismo , Trypanosoma cruzi/genética , Enfermedad de Chagas/parasitología , Cromatina/metabolismo , ADN de Cadena Simple/genética , Humanos , Unión Proteica/genética , Telómero/genética , Homeostasis del Telómero/fisiología , Trypanosoma cruzi/metabolismoRESUMEN
OBJECTIVE: The main objective of this systematic review is to assess the effects of obesity on telomere length. METHODS: The following databases were searched: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), LILACS, SPORTdiscus, and Web of Science from inception to August 2014. The search was performed using the following combinations of terms: telomere AND "overweight" OR "obesity" OR "adiposity," without language restriction. RESULTS: Sixty-three original studies were included in this systematic review, comprising 119,439 subjects. Thirty-nine studies showed either weak or moderate correlation between obesity and telomere length; however, they showed an important heterogeneity. CONCLUSIONS: There is a tendency toward demonstrating negative correlation between obesity and telomere length. The selected studies showed weak to moderate correlation for the main search, and there was an important heterogeneity. For this reason, the causal relationship of obesity and telomere length remains open. Additional controlled longitudinal studies are needed to investigate this issue.
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Obesidad/genética , Homeostasis del Telómero/fisiología , Telómero/metabolismo , Adiposidad/genética , Peso Corporal/genética , Peso Corporal/fisiología , Femenino , Humanos , Leucocitos/metabolismo , Leucocitos/patología , Obesidad/complicaciones , Obesidad/epidemiología , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Sobrepeso/genéticaRESUMEN
The aim of this systematic review is to assess the effects of exercise on telomeres length. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Scopus, LILACS, SPORTDiscus and Web of Science from inception to August 2014. All articles that assessed the effects of exercise in telomere length were included in this review. The search strategy used the following combinations of terms: telomere AND "motor activity" OR exercise OR "physical activity". Two reviewers, working independently, screened all titles and abstracts to identify studies that could meet inclusion criteria. Whenever possible, and if appropriate, we performed a random-effect meta-analysis of study outcomes. Thirty-seven original studies were included in this systematic review, including 41,230 participants. Twenty articles did not find statistically significant association, whereas 15 described a positive association. Two papers found an inverted "U" correlation. There is a tendency toward demonstrating an effect of exercise on telomere length. Few prospective studies were found, many studies did not reach statistical significance and there was an important methodological diversity. For this reason, a possible significant association between physical activity and telomere length remains an open question.
Asunto(s)
Actividad Motora/fisiología , Homeostasis del Telómero/fisiología , Telómero , Humanos , Estadística como AsuntoRESUMEN
BACKGROUND: Lack of weight gain throughout adult life could mimic the beneficial effects of energy restriction in humans. The present study aimed to assess the effects of weight stability or gain, over a period of 10 years, on telomere length, sirtuin 1 and 6 expression, and carotid intima media thickness. METHODS: We studied 148 healthy adults (age range 20-59 years; 101 females) who had an objective record of their weight 10 years before. They were classified as weight losers, weight maintainers, weight gainers and extreme weight gainers. A fasting blood sample was obtained for routine laboratory and isolation of peripheral blood mononuclear cells, to extract DNA and RNA, and to measure telomere length and sirtuin 1 and 6 expression, respectively. Carotid intima media thickness was measured by ultrasound. Body composition was measured by Dual-energy X-ray absorptiometry. RESULTS: In the 10-year period, 24 participants lost weight (17 females), 65 maintained weight (41 females), 25 gained weight (15 females) and 34 were extreme weight gainers (28 females). Female weight gainers had a higher body mass index, waist circumference, total body fat and homeostatic model assessment insulin resistance. Male weight gainers had a higher hip circumference and total body fat. No differences in telomere length, sirtuin 1 expression and carotid intima media thickness were observed between weight gainers and maintainers. CONCLUSIONS: No effect of weight maintenance or gain was observed on metabolic and vascular markers of ageing.
Asunto(s)
Grosor Intima-Media Carotídeo , Expresión Génica , Sirtuina 1/genética , Sirtuinas/genética , Homeostasis del Telómero/fisiología , Aumento de Peso/fisiología , Adulto , Envejecimiento/fisiología , Composición Corporal , Índice de Masa Corporal , Peso Corporal , ADN/sangre , Registros de Dieta , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN/sangre , Circunferencia de la Cintura , Pérdida de PesoRESUMEN
OBJECTIVE: To analyze whether leukocyte telomere length (LTL) is impaired in women with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: Hospital. PATIENT(S): A total of 274 women, including 150 patients with PCOS and 124 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Body mass index (BMI), waist circumference, systemic arterial pressure, lipid profile, E(2), LH, T, androstenedione, PRL, TSH, sex hormone-binding globulin, C-reactive protein (CRP), homocysteine, free androgen index, and the homeostatic model of insulin sensitivity (HOMA-IR) index were analyzed. The LTL evaluation was measured by quantitative polymerase chain reaction. RESULT(S): The PCOS group had higher values for weight, BMI, waist circumference, systolic arterial pressure, triglycerides, LH, T, insulin, CRP, free androgen index, and HOMA-IR compared with the control group. Sex hormone-binding globulin and E(2) levels were lower in the PCOS group than in the control group. The LTL did not differ between groups. Age, BMI, and HOMA-IR had no significant effect on LTL. The inflammatory biomarkers CRP and homocysteine were negatively correlated with LTL in patients with PCOS. CONCLUSION(S): Our results showed no differences in LTL between patients with PCOS and controls, but CRP and homocysteine biomarkers negatively correlated with LTL in the PCOS group.
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Mediadores de Inflamación/sangre , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/diagnóstico , Homeostasis del Telómero/fisiología , Telómero/metabolismo , Adolescente , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Adulto JovenAsunto(s)
Envejecimiento/sangre , Envejecimiento/fisiología , Proteína C-Reactiva/metabolismo , Frecuencia Cardíaca/fisiología , Homeostasis del Telómero/fisiología , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Telómero/fisiología , Adulto JovenRESUMEN
BACKGROUND: Recently, a direct correlation with telomere length, proliferative potential and telomerase activity has been found in the process of aging in peripheral blood cells. The objective of the study was to evaluate telomere length and proliferative potential in peripheral blood mononuclear cells (PBMCs) after stimulation with Concanavalin A (ConA) of young adults compared with older adults. METHODS: Blood samples were obtained from 20 healthy young males (20-25 years old) (group Y) and 20 males (60-65 years old) (group O). We compared PBMC proliferation before and after stimulation with ConA. DNA was isolated from cells separated before and after culture with ConA for telomeric measurement by real-time polymerase chain reaction. RESULTS: In vitro stimulation of PBMCs from young subjects induced an increase of telomere length as well as a higher replicative capacity of cell proliferation. Samples from older adults showed higher loss of telomeric DNA (p = 0.03) and higher levels of senescent (≤6.2 kb) telomeric DNA (p = 0.02) and displayed a marked decrease of proliferation capacity. Viability cell counts and CFSE tracking in 72-h-old cell cultures indicated that group O PBMCs (CD8+ and CD4+ T cells) underwent fewer mitotic cycles and had shorter telomeres than group Y (p = 0.04). CONCLUSIONS: Our findings confirm that telomere length in older-age adults is shorter than in younger subjects. After stimulation with ConA, cells are not restored to the previous telomere length and undergo replicative senescence. This is in sharp contrast to the response observed in young adults after ConA stimulation where cells increase in telomere length and replicative capacity. The mechanisms involved in this phenomenon are not yet clear and merit further investigation.
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Envejecimiento/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Concanavalina A/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Homeostasis del Telómero/efectos de los fármacos , Adulto , Anciano , Envejecimiento/fisiología , Células Cultivadas , Humanos , Leucocitos Mononucleares/fisiología , Masculino , Persona de Mediana Edad , Homeostasis del Telómero/fisiología , Adulto JovenRESUMEN
Telomerase is the enzyme responsible for maintenance of the length of telomeres by addition of guanine-rich repetitive sequences. Telomerase activity is exhibited in gametes and stem and tumor cells. In human somatic cells, proliferation potential is strictly limited and senescence follows approximately 50-70 cell divisions. In most tumor cells, on the contrary, replication potential is unlimited. The key role in this process of the system of the telomere length maintenance with involvement of telomerase is still poorly studied. Undoubtedly, DNA polymerase is not capable of completely copying DNA at the very ends of chromosomes; therefore, approximately 50 nucleotides are lost during each cell cycle, which results in gradual telomere length shortening. Critically short telomeres cause senescence, following crisis and cell death. However, in tumor cells the system of telomere length maintenance is activated. Much work has been done regarding the complex telomere/telomerase as a unique target, highly specific in cancer cells. Telomeres have additional proteins that regulate the binding of telomerase. Telomerase, also associates with a number of proteins forming the sheltering complex having a central role in telomerase activity. This review focuses on the structure and function of the telomere/telomerase complex and its altered behavior leading to disease, mainly cancer. Although telomerase therapeutics are not approved yet for clinical use, we can assume that based on the promising in vitro and in vivo results and successful clinical trials, it can be predicted that telomerase therapeutics will be utilized soon in the combat against malignancies and degenerative diseases. The active search for modulators is justified, because the telomere/telomerase system is an extremely promising target offering possibilities to decrease or increase the viability of the cell for therapeutic purposes.