Long- and Short-Term Exposures to PM10 Can Shorten Telomere Length in Individuals Affected by Overweight and Obesity.
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ABSTRACT:
SUBMITTER: Carugno M
PROVIDER: S-EPMC8400348 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionTelomere length, a marker for biological aging, is implicated with diabetic kidney disease (DKD); however, the association between telomere length and albuminuria progression among Asian patients with type 2 diabetes (T2D) is not well understood. Here, we aim to study whether leukocyte telomere length (LTL) may independently predict albuminuria progression in patients with T2D with preserved renal filtration function (estimated GFR >60 ml/min per 1.73 m2 and urine albumin-to-creatinine ratio [uACR] <300 mg/g).MethodsThe baseline LTL was measured by real-time polymerase chain reaction in the SMART2D cohort (n = 691) with a median follow-up of 3 years. Albuminuria progression was defined as a change in albuminuria category to a higher category and at least 30% increase in uACR from baseline in 3 years.ResultsProgressors (n = 123) had significantly shorter median LTL compared with nonprogressors (n = 568) (0.58 [0.38-0.79] vs. 0.62 [0.45-0.88], P = 0.039). Compared with subjects with longer LTL (fourth quartile), subjects with shorter LTL (first quartile) had 1.93-fold (1.04-3.60, P = 0.038) increased risk for albuminuria progression after adjustment for traditional risk factors. The association of LTL with microalbuminuria to macroalbuminuria progression was stronger than its association with normoalbuminuria to microalbuminuria (odds ratio [OR]: 1.54; 95% confidence interval [CI]: 1.02-2.32; P = 0.042 vs. OR: 1.13; 95% CI: 0.91-1.40; P = 0.263 per 1-SD decrement in natural log-transformed LTL).ConclusionTherefore, our results demonstrated that in patients with T2D with preserved renal filtration function, LTL predicts albuminuria progression beyond traditional risk factors, suggesting LTL may be novel biomarker for DKD progression.
| S-EPMC5976822 | biostudies-literature
Project description:The fat mass and obesity-associated (FTO) rs9939609 polymorphism have been associated with the increased metabolic risk and mortality, irrespective of obesity. The mechanism underlying this association is not known. We aimed to evaluate whether the FTO rs9939609 risk variant is independently associated with metabolic risk factors and/or leukocyte telomere length (LTL). We further aimed to investigate whether this relationship is modified by obesity status.A total of 2133 participants were recruited from the Korean Genome and Epidemiology Study. LTL was measured using the real-time quantitative polymerase chain reaction methodology. The FTO rs9939609 polymorphism was genotyped using DNA samples collected at baseline.The proportions of the TT, TA, and AA genotypes were 76.7%, 21.5%, and 1.8%, respectively, and obese subjects comprised 44.5% of the total subjects. Among the 1184 nonobese subjects, body mass index, waist circumference, and visceral fat area were higher in subjects with the FTO risk allele than in noncarriers. In contrast, only high-sensitive C-reactive protein level was associated with the FTO risk allele in the obese subjects. LTL was significantly shorter in carriers of the FTO risk allele compared with noncarriers after controlling for several confounding factors (P?<?.01). Of particular note, this significant association between the FTO risk allele and LTL appeared only in nonobese subjects (P?=?.03). Multivariate linear regression analyses identified older age, low high-density lipoprotein cholesterol level, and the presence of the FTO risk allele as independent risk factors affecting LTL. This finding was evident only in nonobese subjects.The FTO rs9939609 polymorphism is an independent risk factor for obesity and also for biological aging in the nonobese population.
| S-EPMC5627829 | biostudies-literature
Project description:BACKGROUND:Prior research suggests that undernutrition and enteric infections predispose children to stunted growth. Undernutrition and infections have been associated with limited access to healthy diets, lack of sanitation, and access barriers to healthcare - all associated with human rights. Stunting has also been documented to be a major determinant of subsequent obesity and non-communicable diseases. Short leg length relative to stature during adulthood seems to be a good proxy indicator tracking such barriers, and has been reported to be associated with adverse health effects during adulthood. Our objective was to examine the association between relative leg length (as measured by the leg length index, LLI) and measures of adiposity - based on body mass index (BMI) and waist circumference (WC) - in a population of recent Mexican immigrant women to the New York City Area. METHODS:The analysis was based on a cross-sectional survey of 200 Mexican immigrant women aged 18 to 70?years, whose data were collected between April and November 2008; although for purposes of the current study we restricted the sample to those aged 18 to 59?years. The dependent variables were BMI and WC, both transformed into categorical variables. The main independent variable was LLI, and other correlates were controlled for (i.e. age, education, having had children, characteristics of the community of origin, acculturation, chronic conditions, sedentary behaviors, access to fresh fruits and vegetables). Two probit models were estimated: the first one analyzed the effect of LLI on BMI categories and the second one estimated the effect of LLI on WC. RESULTS:The probit assessing the effect of LLI on overweight/obesity suggested that having a short LLI increased the probability of overweight/obesity by 21 percentage points. Results from the probit model estimating the effect of LLI on WC indicated that having a short LLI increased the probability of having abdominal adiposity by 39 percentage points. Both results were statistically significant at p?<?0.05. CONCLUSION:The study found an association between having shorter legs relative to one's height and increased risk of overweight/obesity and abdominal adiposity. Findings support the epidemiological evidence regarding the association between short leg length, early life socioeconomic conditions (i.e. limited access to basic rights), and increased risk of adverse health effects later in life.
| S-EPMC6609393 | biostudies-literature
Project description:This review examines the biology of the Fat mass- and obesity-associated gene (FTO), and the implications of genetic association of FTO SNPs with obesity and genetic aging. Notably, we focus on the role of FTO in the regulation of methylation status as possible regulators of weight gain and genetic aging. We present a theoretical review of the FTO gene with a particular emphasis on associations with UCP2, AMPK, RBL2, IRX3, CUX1, mTORC1 and hormones involved in hunger regulation. These associations are important for dietary behavior regulation and cellular nutrient sensing via amino acids. We suggest that these pathways may also influence telomere regulation. Telomere length (TL) attrition may be influenced by obesity-related inflammation and oxidative stress, and FTO gene-involved pathways. There is additional emerging evidence to suggest that telomere length and obesity are bi-directionally associated. However, the role of obesity risk-related genotypes and associations with TL are not well understood. The FTO gene may influence pathways implicated in regulation of TL, which could help to explain some of the non-consistent relationship between weight phenotype and telomere length that is observed in population studies investigating obesity.
| S-EPMC5580219 | biostudies-literature
Project description:Shorter leukocyte telomere length (LTL) has been associated with a wide range of age-related disorders including cardiovascular disease (CVD) and diabetes. Obesity is an important risk factor for CVD and diabetes. The association of LTL with obesity is not well understood. This study for the first time examines the association of LTL with obesity indices including body mass index, waist circumference, percent body fat, waist-to-hip ratio, and waist-to-height ratio in 3,256 American Indians (14-93 years old, 60% women) participating in the Strong Heart Family Study. Association of LTL with each adiposity index was examined using multivariate generalized linear mixed model, adjusting for chronological age, sex, study center, education, lifestyle (smoking, alcohol consumption, and total energy intake), high-sensitivity C-reactive protein, hypertension and diabetes. Results show that obese participants had significantly shorter LTL than non-obese individuals (age-adjusted P=0.0002). Multivariate analyses demonstrate that LTL was significantly and inversely associated with all of the studied obesity parameters. Our results may shed light on the potential role of biological aging in pathogenesis of obesity and its comorbidities.
| S-EPMC4069265 | biostudies-literature
Project description:quiescent HSCs have an elevated tolerance to accumulate genomic alterations in response to telomere shortening but the transmission of these aberrations to the progenitor cell level is prevented by senescence and apoptosis
2014-12-02 | GSE60164 | GEO
Project description:Osteosarcoma, the most common primary bone tumor, occurs most frequently in adolescents. Chromosomal aneuploidy is common in osteosarcoma cells, suggesting underlying chromosomal instability. Telomeres, located at chromosome ends, are essential for genomic stability; several studies have suggested that germline telomere length (TL) is associated with cancer risk. We hypothesized that TL and/or common genetic variation in telomere biology genes may be associated with risk of osteosarcoma. We investigated TL in peripheral blood DNA and 713 single nucleotide polymorphisms (SNPs) from 39 telomere biology genes in 98 osteosarcoma cases and 69 orthopedic controls. For the genotyping component, we added 1363 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer ScreeningTrial. Short TL was not associated with osteosarcoma risk overall (OR 1.39, P=0.67), although there was a statistically significant association in females (OR 4.35, 95% Cl 1.20-15.74, P=0.03). Genotype analyses identified seven SNPs in TERF1 significantly associated with osteosarcoma risk after Bonferroni correction by gene. These SNPs were highly linked and associated with a reduced risk of osteosarcoma (OR 0.48-0.53, P=0.0001-0.0006). We also investigated associations between TL and telomere gene SNPs in osteosarcoma cases and orthopedic controls. Several SNPs were associated with TL prior to Bonferroni correction; one SNP in NOLA2 and one in MEN1 were marginally non-significant after correction (P(adj)=0.057 and 0.066, respectively). This pilot-study suggests that females with short telomeres may be at increased risk of osteosarcoma, and that SNPs in TERF1 are inversely associated with osteosarcoma risk.
| S-EPMC3077235 | biostudies-literature
Project description:Negative early-life exposures have been linked to a host of poor adult health outcomes, but are such early exposures associated with cellular senescence decades later? This study uses data from the Health and Retirement Study to examine the association between six childhood exposure domains (eg, socioeconomic disadvantage, risky parental behavior) and a biomarker of aging, telomere length, among 4,935 respondents. Telomere length is obtained from DNA of cells found in saliva and is measured as the telomere repeat copy number to single gene copy number ratio (T/S). Men who as children were exposed to risky parental behaviors or who reported risky adolescent behaviors have shorter telomeres (b = -0.031, p = .052; b = -0.041, p = .045, respectively); however, these relationships are attenuated after adjusting for adult risks and resources. Among women, parental substance abuse is associated with shorter telomeres even after adjusting for adult risks and resources (b = -0.041, p = .005). In addition, men and women whose mother lived at least until the age of 85 have longer telomeres than those without a long-lived mother (b = 0.021, p = .045; b = 0.032, p = .005, respectively). Taken together, the ways in which early-life exposures are associated with adult telomeres vary for men and women.
| S-EPMC8355457 | biostudies-literature
Project description:Differences in the toxicity of ambient particulate matter (PM) due to varying particle composition across locations may contribute to variability in results from air pollution epidemiologic studies. Though most studies have used PM mass concentration as the exposure metric, an alternative which accounts for particle toxicity due to varying particle composition may better elucidate whether PM from specific sources is responsible for observed health effects. The oxidative potential (OP) of PM < 10 ?m (PM(10)) was measured as the rate of depletion of the antioxidant reduced glutathione (GSH) in a model of human respiratory tract lining fluid. Using a database of GSH OP measures collected in greater London, U.K. from 2002 to 2006, we developed and validated a predictive spatiotemporal model of the weekly GSH OP of PM(10) that included geographic predictors. Predicted levels of OP were then used in combination with those of weekly PM(10) mass to estimate exposure to PM(10) weighted by its OP. Using cross-validation (CV), brake and tire wear emissions of PM(10) from traffic within 50 m and tailpipe emissions of nitrogen oxides from heavy-goods vehicles within 100 m were important predictors of GSH OP levels. Predictive accuracy of the models was high for PM(10) (CV R(2)=0.83) but only moderate for GSH OP (CV R(2) = 0.44) when comparing weekly levels; however, the GSH OP model predicted spatial trends well (spatial CV R(2) = 0.73). Results suggest that PM(10) emitted from traffic sources, specifically brake and tire wear, has a higher OP than that from other sources, and that this effect is very local, occurring within 50-100 m of roadways.
| S-EPMC3476505 | biostudies-literature
Project description:Inorganic arsenic is a carcinogen whose mode of action may involve telomere dysfunction. Recent epidemiological studies suggest that chronic arsenic exposure is associated with longer telomeres and altered expression of telomere-related genes in peripheral blood. In this study, we evaluated the association of urinary arsenic concentration with expression of telomere-related genes and telomere length in Bangladeshi individuals with a wide range of arsenic exposure through naturally contaminated drinking water.We used linear regression models to estimate associations between urinary arsenic and array-based expression measures for 69 telomere related genes using mononuclear cell RNA samples from 1799 individuals. Association between arsenic exposure and a qPCR-based telomere length measure was assessed among 167 individuals.Urinary arsenic was positively associated with expression of WRN, and negatively associated with TERF2, DKC1, TERF2IP and OBFC1 (all P<0.00035, Bonferroni-corrected threshold). We detected interaction between urinary arsenic and arsenic metabolism efficiency in relation to expression of WRN (P for interaction =0.00008). In addition, we observed that very high arsenic exposure was associated with longer telomeres compared to very low exposure (P=0.02).Our findings suggest that arsenic's carcinogenic mode of action may involve alteration of telomere maintenance and/or telomere damage. This study extends our knowledge regarding the effect of arsenic on telomere length and expression of telomere-related genes.
| S-EPMC4264833 | biostudies-literature