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1.
Psychosom Med ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31688458

RESUMO

OBJECTIVE: Mounting evidence suggests that higher optimism is associated with reduced risk of age-related morbidities and premature mortality. Yet, possible biological mechanisms underlying these associations remain understudied. One hypothesized mechanism is a slower rate of cellular aging, which in turn delays age-related declines in health. METHODS: We used data from two large cohort studies to test the hypothesis that higher optimism is associated with longer leukocyte telomere length. Using cross-sectional data from the Health and Retirement Study (HRS; N=6,417; mean age=70 years) and the Women's Health Initiative (WHI; N=3,582; mean age=63 years), we used linear regression models to examine the association of optimism with relative telomere length (assessed in leukocytes from saliva [HRS] or plasma [WHI]). Models adjusted for sociodemographics, depression, health status, and health behaviors. RESULTS: Considering both optimism and telomere length as continuous variables, we found consistently null associations in both cohorts, regardless of which covariates were included in the models. In models adjusting for demographics, depression, co-morbidities, and health behaviors, optimism was not associated with mean relative telomere length (HRS: ß=-0.002; 95% CI:-0.014, 0.011; WHI: ß=-0.004; 95% CI:-0.017, 0.009). CONCLUSIONS: Findings do not support mean telomere length as a mechanism that explains observed relations of optimism with reduced risk of chronic disease in older adults. Future research is needed to evaluate other potential biological markers and pathways.

2.
PLoS One ; 14(10): e0223891, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622416

RESUMO

RATIONALE: Shorter leukocyte telomere length (LTL) is associated with reduced health-related quality of life and increased risk for acute exacerbations (AEs) and mortality in chronic obstructive pulmonary disease (COPD). Increased physical activity and exercise capacity are associated with reduced risk for AEs and death. However, the relationships between LTL and physical activity, exercise capacity, and AEs in COPD are unknown. METHODS: Data from 3 COPD cohorts were examined: Cohort 1 (n = 112, physical activity intervention trial), Cohorts 2 and 3 (n = 182 and 294, respectively, separate observational studies). Subjects completed a 6-minute walk test (6MWT) and provided blood for LTL assessment using real-time PCR. Physical activity was measured as average daily step count using an accelerometer or pedometer. Number of self-reported AEs was available for 1) the year prior to enrollment (Cohorts 1 and 3) and 2) prospectively after enrollment (all cohorts). Multivariate models examined associations between LTL and average daily step count, 6MWT distance, and AEs. RESULTS: A significant association between longer LTL and increased 6MWT distance was observed in the three combined cohorts (ß = 3x10-5, p = 0.045). No association between LTL and average daily step count was observed. Shorter LTL was associated with an increased number of AEs in the year prior to enrollment (Cohorts 1 and 3 combined, ß = -1.93, p = 0.04) and with prospective AEs (Cohort 3, ß = -1.3388, p = 0.0003). CONCLUSIONS: Among COPD patients, increased LTL is associated with higher exercise capacity, but not physical activity. Shorter LTL was associated with AEs in a subgroup of cohorts.

3.
Carcinogenesis ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31556446

RESUMO

Mitochondrial DNA (mtDNA) is susceptible to oxidative stress and mutation. Few epidemiological studies have assessed the relationship between mtDNA copy number (mtDNAcn) and risk of colorectal cancer (CRC), with inconsistent findings. In this study, we examined the association between pre-diagnostic leukocyte mtDNAcn and CRC risk in a case-control study of 324 female cases and 658 matched controls nested within the Nurses' Health Study (NHS). Relative mtDNAcn in peripheral blood leukocytes was measured by quantitative PCR-based assay. Conditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association of interest. Results showed lower log-mtDNAcn was significantly associated with increased risk of CRC, in a dose-dependent relationship (P for trend < 0.0001). Compared to the 4th quartile, multivariable-adjusted OR (95% CI) was 1.10 (0.69, 1.76) for the 3rd quartile, 1.40 (0.89, 2.19) for the 2nd quartile, and 2.19 (1.43, 3.35) for the 1st quartile. In analysis by anatomic subsite of CRC, we found a significant inverse association for proximal colon cancer [lowest vs. highest quartile, multivariable-adjusted OR (95% CI) = 3.31 (1.70, 6.45), P for trend = 0.0003]. Additionally, stratified analysis according to the follow-up time since blood collection showed that the inverse association between mtDNAcn and CRC remained significant among individuals with ≥ 5 years' follow-up, and marginally significant among those with ≥ 10 years' follow-up since mtDNAcn testing, suggesting that mtDNAcn may serve as a long-term predictor for risk of CRC. In conclusion, pre-diagnostic leukocyte mtDNAcn was inversely associated with CRC risk. Further basic experimental studies are needed to explore the underlying biological mechanisms linking mtDNAcn to CRC carcinogenesis.

4.
Spinal Cord ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383950

RESUMO

STUDY DESIGN: Cross-sectional study OBJECTIVES: To determine clinical factors associated with telomere length in persons with chronic spinal cord injury (SCI). SETTING: Veterans Affairs Medical Center, Boston, MA. METHODS: Two hundred seventy-eight participants with chronic SCI provided blood samples for measurement of C-reactive protein (CRP), interleukin-6 (IL-6), and telomere length, completed respiratory health questionnaires, underwent dual X-ray absorptiometry (DXA) to assess body fat, and completed spirometry. High-throughput real-time PCR assays were used to assess telomere length in leukocyte genomic DNA. Linear regression models were used to assess cross-sectional associations with telomere length. RESULTS: Telomere length was inversely related to age (p < 0.0001). In age-adjusted models, gender, race, injury duration, %-total and %-trunk fat, body mass index (BMI), %-predicted forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), chronic cough or phlegm, CRP, IL-6, wheeze, smoking, diabetes, heart disease, chronic obstructive pulmonary disease (COPD), skin ulcer, urinary tract infection (UTI), or chest illness history were not significantly associated with telomere length. There was a suggestive age-adjusted association between persons with the most severe SCI (cervical motor complete and AIS C) and shorter telomere length (p = 0.055), an effect equivalent to ~8.4 years of premature aging. There were similar age-adjusted associations with telomere length between persons using a wheelchair (p = 0.059) and persons with chronic urinary catheter use (p = 0.082) compared to persons without these characteristics. CONCLUSIONS: Our results suggest that clinical characteristics such as decreased mobility and bladder dysfunction that are common in individuals with more severe SCI are associated with shorter telomere length.

5.
Cancer Epidemiol Biomarkers Prev ; 28(11): 1868-1875, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31427306

RESUMO

BACKGROUND: Leukocyte telomere length has been associated with risk of subsequent pancreatic cancer. Few prospective studies have evaluated the association of prediagnostic leukocyte telomere length with pancreatic cancer survival. METHODS: We prospectively examined the association of prediagnostic leukocyte telomere length with overall survival (OS) time among 423 participants diagnosed with pancreatic adenocarcinoma between 1984 and 2008 within the Health Professionals Follow-up Study, Nurses' Health Study, Physicians' Health Study, and Women's Health Initiative. We measured prediagnostic leukocyte telomere length in banked blood samples using quantitative PCR. Cox proportional hazards models were used to estimate HRs for OS with adjustment for potential confounders. We also evaluated 10 SNPs at the telomerase reverse transcriptase locus. RESULTS: Shorter prediagnostic leukocyte telomere length was associated with reduced OS among patients with pancreatic cancer (P trend = 0.04). The multivariable-adjusted HR for OS comparing the lowest with highest quintiles of leukocyte telomere length was 1.39 (95% confidence interval, 1.01-1.93), corresponding to a 3-month difference in median OS time. In an analysis excluding cases with blood collected within 2 years of cancer diagnosis, the association was moderately stronger (HR, 1.55; 95% confidence interval, 1.09-2.21; comparing the lowest with highest quintiles; P trend = 0.01). No prognostic association or effect modification for the prognostic association of prediagnostic leukocyte telomere length was noted in relation to the studied SNPs. CONCLUSIONS: Prediagnostic leukocyte telomere length was associated with pancreatic cancer survival. IMPACT: Prediagnostic leukocyte telomere length can be a prognostic biomarker in pancreatic cancer.

6.
Ann Epidemiol ; 36: 33-39, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31387775

RESUMO

PURPOSE: Telomere length is considered a biomarker of human aging and premature morbidity and mortality which has been associated with chronic stress. METHODS: We assessed the relation between perceived racism and telomere length in the Black Women's Health Study, a follow-up study of U.S. black women begun in 1995. Participants were asked about frequency of "everyday racism" (e.g., "people act as if they think you are not intelligent") and "institutional racism" (e.g., "ever treated unfairly due to race by police"). Using quantitative real-time polymerase chain reaction assay, relative telomere lengths (RTL) were measured as the copy number ratio of telomere repeat to a single control gene in 997 participants. Associations of racism variables with log-RTL were estimated by multivariable linear regression, with adjustment for age at blood draw and potential confounders. RESULTS: Participants were aged 40-70 years (mean = 55.6 years), and mean telomere length was 0.77 (range 0.21-1.38). In stratified analyses, there was an inverse association between everyday racism and log-RTL among women who did not discuss their experiences of racism with others (ß = -0.1104; 95% CI = -0.2140 to -0.0067; P = .045). CONCLUSIONS: Everyday racism was associated with shorter telomere length among women who reported not discussing those experiences with others.

7.
Genet Epidemiol ; 43(7): 844-863, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31407831

RESUMO

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.


Assuntos
Doenças Autoimunes/genética , Predisposição Genética para Doença , Linfoma não Hodgkin/genética , Alelos , Feminino , Antígenos HLA/genética , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
8.
Am J Gastroenterol ; 114(6): 893-899, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30950840

RESUMO

OBJECTIVES: Several single-nucleotide polymorphisms (SNPs) have been associated with Barrett's esophagus (BE) risk. In addition, environmental factors including smoking, alcohol consumption, and heartburn increase BE risk. However, data on potential interactions between these genetic and environmental factors on BE risk are scant. Understanding how genes and environmental risk factors interact may provide key insight into the pathophysiology of BE, and potentially identify opportunities for targeted prevention and treatment. The objectives of this study were to examine the main effects and the potential effect modification between known genetic loci (SNPs) and established environmental risk factors for BE. METHODS: We performed a nested case-control study using data on 401 incident BE cases and 436 age-matched controls from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study cohorts, who gave blood and completed biennial questionnaires. Overall, we genotyped 46 SNPs identified in previous BE genome-wide association studies as well as SNPs in candidate genes related to BE susceptibility (i.e., related to excess body fat, fat distribution, factors associated with insulin resistance, and inflammatory mediators). A genetic risk score (GRS) was constructed to evaluate the combined effect of the selected SNPs on BE risk. Interactions between SNPs and BE risk factors were also assessed. RESULTS: We observed a suggestive, but not statistically significant, association between our GRS and BE risk: a one-allele increase in the unweighted GRS increased the risk of BE by a factor of 1.20 (95% confidence interval = 1.00-1.44; P = 0.057). We did not observe any meaningful multiplicative interactions between smoking, alcohol consumption, or heartburn duration and BE genotypes. When we assessed the joint effect of weighted GRS and BE risk factors, we did not observe any significant interaction with alcohol and heartburn duration, whereas smoking showed a significant multiplicative interaction (P = 0.016). CONCLUSIONS: Our results suggest that SNPs associated with BE at genome-wide significant levels can be combined into a GRS with a potential positive association with BE risk.

9.
Science ; 364(6436)2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30975860

RESUMO

To understand the health impact of long-duration spaceflight, one identical twin astronaut was monitored before, during, and after a 1-year mission onboard the International Space Station; his twin served as a genetically matched ground control. Longitudinal assessments identified spaceflight-specific changes, including decreased body mass, telomere elongation, genome instability, carotid artery distension and increased intima-media thickness, altered ocular structure, transcriptional and metabolic changes, DNA methylation changes in immune and oxidative stress-related pathways, gastrointestinal microbiota alterations, and some cognitive decline postflight. Although average telomere length, global gene expression, and microbiome changes returned to near preflight levels within 6 months after return to Earth, increased numbers of short telomeres were observed and expression of some genes was still disrupted. These multiomic, molecular, physiological, and behavioral datasets provide a valuable roadmap of the putative health risks for future human spaceflight.


Assuntos
Adaptação Fisiológica , Astronautas , Voo Espacial , Imunidade Adaptativa , Peso Corporal , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Dano ao DNA , Metilação de DNA , Microbioma Gastrointestinal , Instabilidade Genômica , Humanos , Masculino , Homeostase do Telômero , Fatores de Tempo , Estados Unidos , United States National Aeronautics and Space Administration
10.
Depress Anxiety ; 36(6): 565-575, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30958913

RESUMO

BACKGROUND: Telomeres cap and protect DNA but shorten with each somatic cell division. Aging and environmental and lifestyle factors contribute to the speed of telomere attrition. Current evidence suggests a link between relative telomere length (RTL) and depression but the directionality of the relationship remains unclear. We prospectively examined associations between RTL and subsequent depressive symptom trajectories. METHODS: Among 8,801 women of the Nurses' Health Study, depressive symptoms were measured every 4 years from 1992 to 2012; group-based trajectories of symptoms were identified using latent class growth-curve analysis. Multinomial logistic models were used to relate midlife RTLs to the probabilities of assignment to subsequent depressive symptom trajectory groups. RESULTS: We identified four depressive symptom trajectory groups: minimal depressive symptoms (62%), worsening depressive symptoms (14%), improving depressive symptoms (19%), and persistent-severe depressive symptoms (5%). Longer midlife RTLs were related to significantly lower odds of being in the worsening symptoms trajectory versus minimal trajectory but not to other trajectories. In comparison with being in the minimal symptoms group, the multivariable-adjusted odds ratio of being in the worsening depressive symptoms group was 0.78 (95% confidence interval, 0.62-0.97; p = 0.02), for every standard deviation increase in baseline RTL. CONCLUSIONS: In this large prospective study of generally healthy women, longer telomeres at midlife were associated with significantly lower risk of a subsequent trajectory of worsening mood symptoms over 20 years. The results raise the possibility of telomere shortening as a novel contributing factor to late-life depression.


Assuntos
Envelhecimento/genética , Envelhecimento/psicologia , Depressão/diagnóstico , Depressão/genética , Encurtamento do Telômero/fisiologia , Telômero/metabolismo , Adulto , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/genética , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Telômero/genética , Encurtamento do Telômero/genética
11.
Transl Psychiatry ; 9(1): 118, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30886137

RESUMO

Relations of DNA methylation markers to other biological aging markers and to psychosocial, behavioral, and health measures remain unclear. The sample included 23 participants (n = 11 cases with psychiatric diagnoses and n = 12 controls without current or lifetime psychiatric disorder), balanced by age and sex. Genomic DNA was extracted from blood samples; the following were performed: genome-wide DNA methylation assay using Illumina 850k methylationEPIC; PCR assays for relative telomere length (RTL) and mitochondrial DNA copy number (mtCN). Exposures were: case status; depression and anxiety symptoms; psychosocial support; subjective and objective cognition. Outcomes were: DNA methylation age (DNAm age); RTL; mtCN; extrinsic and intrinsic epigenetic age acceleration (EEAA and IEAA). Stronger correlation with chronological age was observed for DNAm age (ρ = 0.86; p < 0.0001) compared to RTL (ρ = -0.53; p < 0.01); mtCN was not correlated with age. DNAm age was more strongly correlated with behavioral and health variables than RTL or mtCN; e.g., correlations with DNAm age: body mass index (ρ = 0.36; p = 0.10); smoking pack-years (ρ = 0.37; p = 0.08); physical activity (ρ = -0.56; p = 0.01); alcohol intake (ρ = 0.56; p = 0.01). DNAm age was inversely correlated with psychosocial support (ρ = -0.42; p = 0.048) and Modified Mini-Mental State score (ρ = -0.44; p = 0.01). Anxiety, psychosocial support, and objective cognition were significantly related to accelerated aging; depression and subjective cognition were not. In conclusion, DNAm age correlated more strongly with chronological age and key psychosocial, behavioral, and health variables than RTL or mtCN. Signals for associations with epigenetic aging were observed for psychosocial and neurobehavioral variables.

12.
Am J Clin Nutr ; 109(2): 424-432, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30721920

RESUMO

Background: Mitochondrial dysfunction is an important component of the aging process and has been implicated in the development of many human diseases. Mitochondrial DNA copy number (mtDNAcn), an indirect biomarker of mitochondrial function, is sensitive to oxidative damage. Few population-based studies have investigated the impact of fruit and vegetable consumption and cigarette smoke (2 major sources of exogenous antioxidants and oxidants) on leukocyte mtDNAcn. Objectives: We investigated the association between fruit and vegetable consumption, cigarette smoke, and leukocyte mtDNAcn based on data from the Nurses' Health Study (NHS). Methods: Data from 2769 disease-free women in the NHS were used to examine the cross-sectional associations between dietary sources of antioxidants, cigarette smoke, and leukocyte mtDNAcn. In vitro cell-based experiments were conducted to support the findings from the population-based study. Results: In the multivariable-adjusted model, both whole-fruit consumption and intake of flavanones (a group of antioxidants abundant in fruit) were positively associated with leukocyte mtDNAcn (P-trend = 0.005 and 0.02, respectively), whereas pack-years of smoking and smoking duration were inversely associated with leukocyte mtDNAcn (P-trend = 0.01 and 0.007, respectively). These findings are supported by in vitro cell-based experiments showing that the administration of naringin, a major flavanone in fruit, led to a substantial increase in mtDNAcn in human leukocytes, whereas exposure to nicotine-derived nitrosamine ketone, a key carcinogenic ingredient of cigarette smoke, resulted in a significant decrease in mtDNAcn of cells (all P < 0.05). Further in vitro studies showed that alterations in leukocyte mtDNAcn were functionally linked to the modulation of mitochondrial biogenesis and function. Conclusions: Fruit consumption and intake of dietary flavanones were associated with increased leukocyte mtDNAcn, whereas cigarette smoking was associated with decreased leukocyte mtDNAcn, which is a promising biomarker for oxidative stress-related health outcomes.


Assuntos
Fumar Cigarros/efeitos adversos , Variações do Número de Cópias de DNA , DNA Mitocondrial , Dieta , Leucócitos , Mitocôndrias/fisiologia , Fumaça/efeitos adversos , Envelhecimento , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Estudos Transversais , Comportamento Alimentar , Feminino , Flavanonas/farmacologia , Frutas/química , Humanos , Cetonas/efeitos adversos , Pessoa de Meia-Idade , Mitocôndrias/genética , Nicotina/efeitos adversos , Nitrosaminas/efeitos adversos , Oxidantes/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Fumaça/análise , Produtos do Tabaco/efeitos adversos , Verduras/química
13.
Environ Res ; 168: 507-513, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30477822

RESUMO

INTRODUCTION: Particulate air pollution is probably causally related to increased risk of cardiovascular disease. Plasma homocysteine is an established cardiovascular disease risk factor. Recent studies show that exposure to particulate air pollution is associated with plasma homocysteine levels in adults but no studies on the association between prenatal air pollution and neonatal homocysteine levels exist. METHODS: In 609 newborns of the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort, we investigated the association between prenatal particulate matter exposure with a diameter ≤ 2.5 µm (PM2.5) and cord plasma homocysteine levels, and in a subset (n = 490) we studied the interaction with 11 single nucleotide polymorphism (SNPs) in oxidative stress-related genes (CAT, COMT, GSTP1, SOD2, NQO1 and HFE), through multiple linear regression. PM2.5 levels were obtained using a high resolution spatial temporal interpolation method. Homocysteine levels were measured by the homocysteine enzymatic assay on a Roche/Hitachi cobas c system. SNPs were assessed on the Biotrove OpenArray SNP genotyping platform. RESULTS: In multivariable-adjusted models, cord plasma homocysteine levels were 8.1% higher (95% CI: 1.9 to 14.3%; p = 0.01) for each 5 µg/m³ increment in average PM2.5 exposure during the entire pregnancy. With regard to pregnancy trimesters, there was only an association in the 2nd trimester: 3.6% (95% CI: 0.9% to 6.4%; p = 0.01). The positive association between PM2.5 in and homocysteine was (borderline) statistically significantly modified by genetic variants in MnSOD (p interaction = 0.02), GSTP1 (p interaction = 0.07) and the sum score of the 3 studied SNPs in the CAT gene (p interaction=0.09), suggesting oxidative stress as an underlying mechanism of action. CONCLUSIONS: Exposure to particulate air pollution in utero is associated with higher cord blood homocysteine levels, possibly through generating oxidative stress. Increased air pollution-induced homocysteine levels in early life might predispose for cardiovascular and other diseases later in life.


Assuntos
Poluentes Atmosféricos , Poluição do Ar/estatística & dados numéricos , Homocisteína/sangue , Exposição Materna/estatística & dados numéricos , Adulto , Feminino , Sangue Fetal , Humanos , Recém-Nascido , Material Particulado , Gravidez
14.
Ageing Res Rev ; 49: 1-10, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30448616

RESUMO

The Mediterranean diet (MD) is a gold standard for nutrition and the most evidence-based diet to delay the onset of age-associated pathologies. Telomeres are the heterochromatic repeat regions found at the ends of eukaryotic chromosomes, whose length is considered a reliable hallmark of biological ageing. Telomere shortening is, at least in part, a modifiable factor and there is evidence that adherence to the MD is associated with longer telomeres. Data from several studies indicate an association between "inflammatory/oxidative status" and telomere length (TL). The MD, as a complex exposome with thousands of nutrients and phytochemicals, may positively influence telomere attrition by reducing inflammation and oxidative stress. However, it is unclear whether the protective effects on TL provided by the MD result from its individual constituents or some combination of these. Furthermore, these properties of the MD and its components are not yet fully validated by clinical endpoints in randomized trials or observational studies. Here, we summarize the data from experimental and population-based studies on the effects of the MD on TL maintenance. We will both highlight the possible role of the MD in the prevention of age-associated diseases, and attempt to identify certain aspects of the diet that are particularly important for telomere maintenance.

15.
J Trauma Stress ; 31(5): 676-686, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30338579

RESUMO

Traumatic stress is thought to be associated with shortened telomere length (TL) in leukocytes, an age-related marker of increased risk for cellular senescence, although findings thus far have been mixed. We assessed associations between posttraumatic stress disorder (PTSD) symptom severity, temperament, and TL in a sample of 453 White, non-Hispanic, middle-aged, trauma-exposed male and female veterans and civilians. Given that prior research has suggested an association between PTSD and accelerated cellular age, we also examined associations between TL and an index of accelerated cellular age derived from DNA methylation data (DNAm age). Analyses revealed that, controlling for chronological age, PTSD was not directly associated with TL but rather this association was moderated by age, ß = -.14, p = .003, ΔR2 = .02. Specifically, PTSD severity evidenced a stronger negative association with TL among relatively older participants (≥ 55 years of age). In a subset of veterans with data pertaining to temperament (n = 150), positive emotionality, and, specifically, a drive toward achievement, ß = .26, p = .002, ΔR2 = .06, were positively associated with TL. There was no evidence of an association between age-adjusted TL and accelerated DNAm age. Collectively, these results indicate that older adults may be more vulnerable to the negative health effects of PTSD but that traits such as achievement, resilience, and psychological hardiness may be protective. These findings underscore the importance of identifying reliable biomarkers of cellular aging and senescence and of determining the biological mechanisms that contribute to stress-related disease and decline.

16.
Epigenetics ; : 1-16, 2018 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-30270718

RESUMO

Assessing DNA methylation profiles in human blood has become a major focus of epidemiologic inquiry. Understanding variability in CpG-specific DNA methylation over moderate periods of time is a critical first step in identifying CpG sites that are candidates for DNA methylation-based etiologic, diagnostic and prognostic predictors of pathogenesis. Using the Illumina MethylationEPIC [850K] BeadArray, DNA methylation was profiled in paired whole blood samples collected approximately 1 year apart from 35 healthy women enrolled in the Nurses Study II cohort. The median intraclass correlation coefficient (ICC) across all CpG loci was 0.19 [Interquartile Range (IQR) 0.00-0.50]; 74.8% of ICCs were in the low range (0-0.5), 16.9% in the mid-range of ICCs (0.5-0.8), and 8.3% in the high-range of ICCs (0.8-1). ICCs were similar for CpG probes on the 450K Illumina array (median 0.17) and the new probes added to the 850K array (median 0.21). ICCs for CpG loci on the sex chromosomes and known metastable epialleles were high (median 0.71, 0.97, respectively), and ICCs among methylation quantitative trait loci (mQTL) CpGs were significantly higher as compared to non-mQTL CpGs (median 0.73, 0.16, respectively, P < 2 × 10-16). We observed wide variation in DNA methylation stability over a 1-year period. Probes considered non-stable, due to substantial variation over a moderate period of time and with minimal variability across individuals could be removed in large epidemiological studies. Moreover, adjusting for technical variation that arises from using high-dimensional arrays is critical.

17.
J Nutr Biochem ; 61: 33-39, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30179727

RESUMO

We evaluated the short-term effects of a flavanol-rich cocoa (FRC) on lipid profile and selected oxidative stress biomarkers such as oxidized low-density lipoprotein (oxLDL), glutathione (GSH), and F2-isoprostane. We also assessed whether FRC modulates plasma levels of polyunsaturated fatty acids (PUFA) in healthy individuals. The subjects (n=48) were randomly assigned to a low-cocoa group (1 g/d; ~55 mg flavanols) (n=16), middle-cocoa group (2 g/d; ~110 mg flavanols) (n=16), or a high-cocoa group (4 g/d; ~220 mg flavanols) (n=16). The samples were collected at baseline, at 1, 2, and 4 h post initial consumption of FRC, and after 4 weeks of FRC supplementation. The peak plasma concentration of (-)-epicatechin metabolites reached a maximum level (578±61 nM; P<.05) at 2 h after ingestion of FRC. After 4 weeks, total cholesterol (-12.37±6.63; P<.0001), triglycerides (-3.81±2.45; P<.0001), plasma LDL (-14.98±6.77; P<.0001), and oxLDL (-95.61±41.69; P<.0001) decreased in the high-cocoa group, compared with baseline. We also found that plasma high-density lipoprotein (HDL) (+3.37±2.06; P<.0001) concentrations increased significantly in the same group. Total GSH significantly increased in all FRC-treated groups (+209.73±146.8; P<.0001), while urinary F2-isoprostane levels decreased in the middle- (-0.73±0.16; P<.0001) and high-cocoa (-1.62±0.61; P<.0001) groups. At the end of the four-week study, a significant reduction of arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio was observed in the low-(-2.62±2.93; P=.003), middle- (-5.24±2.75; P<.0001) and high-cocoa (-7.76±4.96; P<.0001) groups, compared with baseline. Despite the small sample size used in this study, these data extend previous clinical and experimental studies, providing new insights into the health benefits of cocoa flavanols.

18.
J Psychiatr Res ; 103: 182-188, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29883926

RESUMO

Prior studies have reported significant cross-sectional associations between depression or anxiety and shorter telomere lengths, but the temporality of associations is uncertain. Little is known regarding whether shorter telomere length is related to increased risk of developing depression or anxiety. In this study, using the genetic tool of polygenic risk score (PRS), we evaluated the association between genetic predisposition to shorter telomere length and the risks of lifetime clinically significant depression (defined by self-reported clinician/physician diagnosis, antidepressant use, and/or presence of severe depressive symptoms) and of clinically meaningful anxiety symptoms among 17,693 female participants of European ancestry. The weighted PRS of telomere lengths (TLs) combined the dosage of nine alleles that were significantly associated with inter-individual variation in TLs in published genome-wide association studies. Higher score of PRS, corresponding to shorter TL in the literature, was significantly associated with shorter relative TLs (p = 0.008). However, higher PRS was not associated with the lifetime risk of either depression or anxiety. Furthermore, higher PRS was not associated with long-term patterns of depressive symptom trajectories or specifically with later-life onset of depression or anxiety. In summary, this study did not observe a significant association between genetic predisposition to shorter telomere length and risk of depression and anxiety in a large sample of mid-life and older white women. However, these genetic variants jointly account for a limited proportion of interpersonal variation in leukocyte telomere length. Future studies will need to incorporate more genetic variants to improve the accuracy of predicted power, as such data become available.

20.
Eur J Epidemiol ; 33(5): 485-495, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29619669

RESUMO

Adiposity may cause adverse health outcomes by increasing oxidative stress and systemic inflammation, which can be reflected by altered telomere length (TL) and mitochondrial DNA copy number (mtCN) in peripheral blood leukocytes. However, little is known about the influence of lifetime adiposity on TL and mtCN in later life. This study was performed to investigate the associations of lifetime adiposity with leukocyte TL and mtCN in 9613 participants from the Nurses' Health Study. A group-based trajectory modelling approach was used to create trajectories of body shape from age 5 through 60 years, and a genetic risk score (GRS) was created based on 97 known adiposity susceptibility variants. Associations of body shape trajectories and GRS with dichotomized TL and mtCN were assessed by logistic regression models. After adjustment for lifestyle and dietary factors, compared with the lean-stable group, the lean-marked increase group had higher odds of having below-median TL (OR = 1.18, 95% CI 1.04, 1.35; P = 0.01), and the medium-marked increase group had higher odds of having below-median mtCN (OR = 1.28, 95% CI 1.00, 1.64; P = 0.047). There was a suggestive trend toward lower mtCN across the GRS quartiles (P for trend = 0.07). In conclusion, telomere attrition may be accelerated by marked weight gain in middle life, whereas mtCN is likely to be reduced persistently by adiposity over the life course. The findings indicate the importance of lifetime weight management to preserve functional telomeres and mitochondria.

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