Telomere Length and Oxidative Stress and Its Relation with Metabolic Syndrome Components in the Aging.
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ABSTRACT:
SUBMITTER: Gavia-Garcia G
PROVIDER: S-EPMC8063797 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Previous evidence supports the important role that oxidative stress (OxS) plays in metabolic syndrome (MetS)-related manifestations. We determined the relationship between the number of MetS components and the degree of OxS in MetS patients. In this comparative cross-sectional study from the LIPGENE cohort, a total of 91 MetS patients (43 men and 48 women; aged between 45 and 68 years) were divided into four groups based on the number of MetS components: subjects with 2, 3, 4 and 5 MetS components (n=20, 31, 28 and 12, respectively). We measured ischemic reactive hyperemia (IRH), plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), total nitrite, lipid peroxidation products (LPO), hydrogen peroxide (H2O2), superoxide dismutase (SOD) and glutathione peroxidase (GPx) plasma activities. sVCAM-1, H2O2 and LPO levels were lower in subjects with 2 or 3 MetS components than subjects with 4 or 5 MetS components. IRH and total nitrite levels were higher in subjects with 2 or 3 MetS components than subjects with 4 or 5 MetS components. SOD and GPx activities were lower in subjects with 2 MetS components than subjects with 4 or 5 MetS components. Waist circumference, weight, age, homeostatic model assessment-β, triglycerides (TGs), high-density lipoprotein and sVCAM-1 levels were significantly correlated with SOD activity. MetS subjects with more MetS components may have a higher OxS level. Furthermore, association between SOD activity and MetS components may indicate that this variable could be the most relevant OxS biomarker in patients suffering from MetS and could be used as a predictive tool to determine the degree of the underlying OxS in MetS.
| S-EPMC3701288 | biostudies-literature
Project description:BackgroundRate of reproductive aging may be related to rate of biological aging. Thus, indicators of aging, such as short telomere length, may be more frequent in women with a history suggestive of premature reproductive senescence.MethodsTelomere-specific quantitative PCR was used to assess telomere length in two groups of women with evidence of reproductive aging: (i) patients with idiopathic premature ovarian failure (POF, N = 34) and (ii) women with a history of recurrent miscarriage (RM, N = 95); and two control groups: (1) women from the general population (C1, N = 108) and (2) women who had a healthy pregnancy after 37 years of age (C2, N = 46).ResultsThe RM group had shorter age-adjusted mean telomere length than controls (8.46 versus 8.92 kb in C1 and 9.11 kb in C2, P = 0.0004 and P = 0.02 for C1 and C2, respectively), although short telomeres were not confined to subsets of this group known to have experienced single or multiple trisomic pregnancies. Although sample size is limited, mean telomere length in the POF group was significantly longer than that in C1 (9.58 versus 8.92 kb, P = 0.01).ConclusionsWomen experiencing RM may have shorter telomeres as a consequence of a more rapid rate of aging, or as a reflection of an increased level of cellular stress. Longer telomere length in the POF group may be explained by abnormal hormone exposure, slow cell division rates or autoimmunity in these women. Despite small sample sizes, these results suggest that different manifestations of reproductive aging are likely influenced by distinct physiological factors.
| S-EPMC2667790 | biostudies-literature
Project description:Observational studies have revealed associations between short leucocyte telomere length (LTL), a TL marker in somatic tissues and multiple Metabolic Syndrome (MetS) traits. Animal studies have supported these findings by showing that increased telomere attrition leads to adipose tissue dysfunction and insulin resistance. We investigated the associations between genetically instrumented LTL and MetS traits using Mendelian Randomisation (MR). Fifty-two independent variants identified at FDR<0.05 from a genome-wide association study (GWAS) including 78,592 Europeans and collectively accounting for 2.93% of LTL variance were selected as genetic instruments for LTL. Summary-level data for MetS traits and for the MetS as a binary phenotype were obtained from the largest publicly available GWAS and two-sample MR analyses were used to estimate the associations of LTL with these traits. The combined effect of the genetic instruments was modelled using inverse variance weighted regression and sensitivity analyses with MR-Egger, weighted-median and MR-PRESSO were performed to test for and correct horizonal pleiotropy. Genetically instrumented longer LTL was associated with higher waist-to-hip ratio adjusted for body mass index (β = 0.045 SD, SE = 0.018, p = 0.01), raised systolic (β = 1.529 mmHg, SE = 0.332, p = 4x10-6 ) and diastolic (β = 0.633 mmHg, SE = 0.222, p = 0.004) blood pressure, and increased MetS risk (OR = 1.133, 95% CI 1.057-1.215). Consistent results were obtained in sensitivity analyses, which provided no evidence of unbalanced horizontal pleiotropy. Telomere shortening might not be a major driver of cellular senescence and dysfunction in human adipose tissue. Future experimental studies should examine the mechanistic bases for the links between longer LTL and increased upper-body fat distribution and raised blood pressure.
| S-EPMC8373272 | biostudies-literature
Project description:Alu and LINE-1 elements are retrotransposons with a ubiquitous presence in the human genome that can cause genomic instability, specifically relating to telomere length. Genotoxic agents may induce methylation of retrotransposons, in addition to oxidative DNA damage in the form of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Methylation of retrotransposons induced by these agents may contribute to biliary atresia (BA) etiology. Here, we investigated correlations between global methylation, 8-OHdG, and relative telomere length, as well as reporting on Alu and LINE-1 hypomethylation in BA patients. Alu and LINE-1 hypomethylation were found to be associated with elevated risk of BA (OR?=?4.07; 95% CI: 2.27-7.32; P?<?0.0001 and OR?=?3.51; 95% CI: 1.87-6.59; P?<?0.0001, respectively). Furthermore, LINE-1 methylation was associated with liver stiffness in BA patients (? coefficient?=?-0.17; 95% CI: -0.24 to -0.10; P?<?0.0001). Stratified analysis revealed negative correlations between Alu and LINE-1 methylation and 8-OHdG in BA patients (P?<?0.0001). In contrast, positive relationships were identified between Alu and LINE-1 methylation and relative telomere length in BA patients (P?<?0.0001). These findings suggest that retrotransposon hypomethylation is associated with plasma 8-OHdG and telomere length in BA patients.
| S-EPMC4886632 | biostudies-literature
Project description:Shorter telomeres have been associated with poor health behaviors, age-related diseases, and early mortality. Telomere length is regulated by the enzyme telomerase, and is linked to exposure to proinflammatory cytokines and oxidative stress. In our recent randomized controlled trial, omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation lowered the concentration of serum proinflammatory cytokines. This study assessed whether n-3 PUFA supplementation also affected leukocyte telomere length, telomerase, and oxidative stress. In addition to testing for group differences, changes in the continuous n-6:n-3 PUFA ratio were assessed to account for individual differences in adherence, absorption, and metabolism. The double-blind four-month trial included 106 healthy sedentary overweight middle-aged and older adults who received (1) 2.5g/day n-3 PUFAs, (2) l.25g/day n-3 PUFAs, or (3) placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Supplementation significantly lowered oxidative stress as measured by F2-isoprostanes (p=0.02). The estimated geometric mean log-F2-isoprostanes values were 15% lower in the two supplemented groups compared to placebo. Although group differences for telomerase and telomere length were nonsignificant, changes in the n-6:n-3 PUFA plasma ratios helped clarify the intervention's impact: telomere length increased with decreasing n-6:n-3 ratios, p=0.02. The data suggest that lower n-6:n-3 PUFA ratios can impact cell aging. The triad of inflammation, oxidative stress, and immune cell aging represents important pre-disease mechanisms that may be ameliorated through nutritional interventions. This translational research broadens our understanding of the potential impact of the n-6:n-3 PUFA balance. ClinicalTrials.gov identifier: NCT00385723.
| S-EPMC3545053 | biostudies-literature
Project description:ObjectiveHigh oxidative stress potentially leads to accelerated telomere shortening and consequent premature cell senescence, implicated in type 2 diabetes (T2D) development. Therefore, we studied the association of leukocyte telomere length (LTL) with the presence of T2D, as well as the effect on the patients' LTL of plasma oxidative stress and of variation in UCP2, a gene involved in the mitochondrial production of reactive oxygen species.MethodsMean LTL was determined in 569 Caucasian, 103 South Asian and 70 Afro-Caribbean T2D patients aged from 24 to 92 years, 81 healthy Caucasian male students aged from 18 to 28 years and 367 healthy Caucasian men aged from 40 to 61 years by real-time PCR. Plasma total antioxidant status (TAOS) was measured in the T2D patients by a photometric microassay. The patients were also genotyped for the UCP2 functional variants -866G>A and A55V.ResultsAfro-Carribeans had 510bp longer mean length compared to Caucasians (p<0.0001) and 500bp longer than South Asians (p=0.004). T2D subjects displayed shorter age-adjusted LTL compared to controls [6.94(6.8-7.03) vs. 7.72(7.53-7.9), p<0.001] with subjects in the middle and the lowest tertile of LTL having significantly higher odds ratios for T2D compared to those in the highest tertile [1.50(1.08-2.07) and 5.04(3.63-6.99), respectively, p<0.0001]. In the patients, LTL was correlated negatively with age (r=-0.18, p<0.0001) and positively with TAOS measures (r=0.12, p=0.01) after adjusting for age, while carriers of the UCP2 -866A allele had shorter age-adjusted LTL than common homozygotes [6.86(6.76-6.96)kb vs. 7.03(6.91-7.15)kb, p=0.04].ConclusionThe present data suggest that shorter LTL is associated with the presence of T2D and this could be partially attributed to the high oxidative stress in these patients. The association of the UCP2 functional promoter variant with the LTL implies a link between mitochondrial production of reactive oxygen species and shorter telomere length in T2D.
| S-EPMC2839074 | biostudies-literature
Project description:Individual differences in personality are associated with variation in healthy aging. Health behaviours are often cited as the likely explanation for this association; however, an underlying biological mechanism may also exist. Accelerated leukocyte telomere shortening is implicated in multiple age-related diseases and is associated with chronic activation of the hypothalamus-pituitary-adrenal (HPA) axis, providing a link between stress-related personality differences and adverse health outcomes. However, the effects of the HPA axis are tissue specific. Thus, leukocyte telomere length may not accurately reflect telomere length in disease-relevant tissues. Here, we examined the correlation between stress reactivity and telomere length in heart and brain tissue in young (6-9 month) and aging (18 month) zebrafish. Stress reactivity was assessed by tank diving and through gene expression. Telomere length was assessed using quantitative PCR. We show that aging zebrafish have shorter telomeres in both heart and brain. Telomere length was inversely related to stress reactivity in heart but not brain of aging individuals. These data support the hypotheses that an anxious predisposition contributes to accelerated telomere shortening in heart tissue, which may have important implications for our understanding of age-related heart disease, and that stress reactivity contributes to age-related telomere shortening in a tissue-specific manner.
| S-EPMC7801459 | biostudies-literature
Project description:Previous evidences support that increased oxidative stress (OxS) may play an important role in metabolic syndrome (MetS) and both are closely linked to vascular dysfunction. This study determined whether there is a relationship between endothelial function and relative telomere length (RTL) in MetS subjects. In this cross-sectional study from the LIPGENE cohort, a total of 88 subjects (36 men and 52 women) were divided into four groups by quartiles of telomere length. We measured ischemic reactive hyperemia (IRH), total nitrite (NO) and protein carbonyl (PC) plasma levels, F2-isoprostanes urinary levels, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) plasma activities. IRH and NO plasma levels were higher in subjects with longer RTL (quartiles 3 and 4), while PC plasma levels, F2-isoprostanes urinary levels, and GPx and SOD plasma activities were lower in quartile 4 subjects (longest RTL). Additionally, MetS subjects with longer RTL had greater homeostatic model assessment-? level and lower triglycerides plasma levels. Our results suggest that endothelial dysfunction, associated with high levels of OxS, could be entailed in an increment of telomere attrition. Thus, further support of the molecular and cellular mechanisms involved in vascular dysfunction may contribute to the development of strategies to decelerate vascular aging or prevent cardiovascular disease.
| S-EPMC4150903 | biostudies-literature
Project description:Telomerase is required for long-term telomere maintenance and protection. Using single budding yeast mother cell analyses we found that, even early after telomerase inactivation (ETI), yeast mother cells show transient DNA damage response (DDR) episodes, stochastically altered cell-cycle dynamics, and accelerated mother cell aging. The acceleration of ETI mother cell aging was not explained by increased reactive oxygen species (ROS), Sir protein perturbation, or deprotected telomeres. ETI phenotypes occurred well before the population senescence caused late after telomerase inactivation (LTI). They were morphologically distinct from LTI senescence, were genetically uncoupled from telomere length, and were rescued by elevating dNTP pools. Our combined genetic and single-cell analyses show that, well before critical telomere shortening, telomerase is continuously required to respond to transient DNA replication stress in mother cells and that a lack of telomerase accelerates otherwise normal aging.
| S-EPMC4496004 | biostudies-literature
Project description:Oxidative and inflammatory stress are elevated in obesity and are further augmented in metabolic syndrome. We showed previously that dairy components suppress the adipocyte- and macrophage-mediated generation of reactive oxygen species and inflammatory cytokines and systemic oxidative and inflammatory biomarkers in obesity.The objective of this study was to determine the early (7 d) and sustained (4 and 12 wk) effects of adequate-dairy (AD) compared with low-dairy (LD) diets in subjects with metabolic syndrome.Forty overweight and obese adults with metabolic syndrome were randomly assigned to receive AD (3.5 daily servings) or LD (<0.5 daily servings) weight-maintenance diets for 12 wk. Oxidative and inflammatory biomarkers were assessed at 0, 1, 4, and 12 wk as primary outcomes; body weight and composition were measured at 0, 4, and 12 wk as secondary outcomes.AD decreased malondialdehyde and oxidized LDL at 7 d (35% and 11%, respectively; P < 0.01), with further decreases by 12 wk. Inflammatory markers were suppressed with intake of AD, with decreases in tumor necrosis factor-? at 7 d and further reductions through 12 wk (35%; P < 0.05); decreases in interleukin-6 (21%; P < 0.02) and monocyte chemoattractant protein 1 (14% decrease at 4 wk, 24% decrease at 12 wk; P < 0.05); and a corresponding 55% increase in adiponectin at 12 wk (P < 0.01). LD exerted no effect on oxidative or inflammatory markers. Diet had no effect on body weight; however, AD significantly reduced waist circumference and trunk fat (P < 0.01 for both), and LD exerted no effect.An increase in dairy intake attenuates oxidative and inflammatory stress in metabolic syndrome. This trial was registered at clinicaltrials.gov as NCT01266330.
| S-EPMC3142721 | biostudies-literature