Telomere Length Research Articles

The expression of shelterin genes and telomere repeat analysis and their effect on Alzheimer's disease.

Alzheimer's disease (AD) is an age-related dementia disorder characterized by memory loss and behavioral changes. Maintaining the integrity of telomere shortening in AD is important for cellular survival and homeostasis in all cells, especially glial cells. The shelterin protein complex provides telomere integrity. Measuring the expression levels of shelterin genes and determining the telomere lengths regulated by this complex will reveal their effects on AD progression and adult neurogenesis and will allow the detection of the disease or the determination of the progression process from an accessible tissue. The study population included 111 patients and 91 healthy controls (male and female, < 50 age). The clinical histories (age, gender, hypertension, diabetes mellitus, obesity, cardiovascular disease, MMSE, medication use, family history, sleep disorders, seizure), covariates (HGB, ESR, Na, P, Cl, BUN, CRP, B12, TSH, Glucose, and MRI findings) and the expressional changes of shelterin genes (TERF1, TERF2, TINF2, POT1, TPP1, and RAP1) between the patient and control groups were evaluated relatively. ROC analyses determined the diagnostic power of telomere repeats and gene expressions. In conclusion, upregulation of expression of shleterin complex genes was detected in AD, where telomeres are significantly shorter than in controls (P < 0.05). However, only TERF2 and RAP1 were significant (P < 0.05). A positive relationship was detected between telomere repeats and these genes (P < 0.05). Telomere repeats may be a strong diagnostic criterion to distinguish AD individuals from healthy individuals (AUC = 1.000). The upregulation of TERF2 and RAP1 core genes required for telomere integrity results in the instability of excessively shortened telomeres. Expression silencing of these genes may increase telomerase activity and maintain cellular survival. Also, the detection of telomere repeats has potential in the early diagnosis of AD patients.

Antisenescence Expansion of Mesenchymal Stem Cells Using Piezoelectric β-Poly(vinylidene fluoride) Film-Based Culture.

Regenerative therapies based on mesenchymal stem cells (MSCs) show promise in treating a wide range of disorders. However, the replicative senescence of MSCs during in vitro expansion poses a challenge to obtaining a substantial quantity of high-quality MSCs. In this investigation, a piezoelectric β-poly(vinylidene fluoride) film-based culture plate (β-CP) was developed with an antisenescence effect on cultured human umbilical cord-derived MSCs. Compared to traditional tissue culture plates (TCPs) and α-poly(vinylidene fluoride) film-based culture plates, the senescence markers of p21, p53, interleukin-6 and insulin-like growth factor-binding protein-7, stemness markers of OCT4 and NANOG, and telomere length of MSCs cultured on β-CPs were significantly improved. Additionally, MSCs at passage 18 cultured on β-CPs showed significantly better multipotency and pro-angiogenic capacities in vitro, and higher wound healing abilities in a mouse model. Mechanistically, β-CPs rejuvenated senescent MSCs by improving mitochondrial functions and mitigating oxidative and glycoxidative stresses. Overall, this study presents β-CPs as a promising approach for efficient and straightforward antisenescence expansion of MSCs while preserving their stemness, thereby holding great potential for large-scale production of MSCs for clinical application in cell therapies.

Exposing telomere length's impact on malnutrition risk among older adults residing in the community: Insights from cross-sectional data analysis.

Successful aging is associated with an increase in life expectancy. For a better understanding of the aging process, recognize the relationship between telomere length and nutritional status is a novel approach in geriatric science. Telomers shortening coincides with a decrease in life expectancy, and an increased risk of malnutrition-related diseases. The goal of this study was to investigate whether a shorter telomere length is associated with a greater likelihood of malnutrition in community-dwelling older adults. A cross-sectional study with a probabilistic sample of 448 older people aged 60 years old or over, and living in the urban area of an inland Brazilian municipality was conducted. The information was gathered in two stages: a) a personal interview was conducted to obtain sociodemographic, cognitive, and functional autonomy data. The Mini Nutritional Assessment was used to assess the risk of malnutrition. b) a blood sample was taken to proceed with the relative quantitative study of telomere length using real-time qPCR method. The differences between the groups were estimated using Pearson's v2 and Fisher's exact tests. In the data analysis, descriptive statistics and multiple logistic regression were applied. In 34.15% of the total sample, malnutrition was recognized as a risk factor. Older people with the shortest telomere length had more chances of getting malnutrition (OR = 1.63; IC:95% = 1.04-2.55) compared to those with longer telomeres, independent of age groups, family income, multimorbidity, cognitive decline, and depressive symptoms. The creation of clinical trials and the implementation of therapies to reduce the risk of malnutrition will be aided using the telomere length as an aging innovative biomarker, connected with nutritional status.

Association between monocyte to high-density lipoprotein cholesterol ratio and telomere length: based on NHANES 1999–2002

BackgroundTelomere length is closely associated with the occurrence and development of cardiovascular and other diseases. Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel indicator of inflammation, oxidative stress, and metabolic syndrome, with some predictive ability for related disease risks in clinical practice. However, there is no research on the correlation between these two factors.MethodsUsing data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002, we conducted analysis and research on the correlation between MHR and telomere length using the Kruskal-Wallis H test, Spearman rank correlation analysis, and partial correlation analysis. Weighted linear regression analysis assessed the strength of the association between the two variables, while restricted cubic spline regression (RCS) explored potential nonlinear relationships between them.ResultsThe results of correlation analysis showed that MHR levels were negatively correlated with telomere length (ρ=-0.083, P < 0.001), and this relationship remained statistically significant after controlling for other covariates (P all < 0.001). Weighted linear regression analysis showed that after adjusting for all covariates, MHR remained negatively associated with telomere length (β = -0.020; 95% CI: -0.039 to -0.002; P = 0.037). Subgroup analysis shows that the negative association between MHR and telomere length appeared more striking among females (\U0001d6fd = -0.024; 95%CI: -0.050 to 0.001; P = 0.058), the Non-Hispanic White (\U0001d6fd = -0.022; 95%CI: -0.045 to 0.002; P = 0.066), and other race (\U0001d6fd = -0.067; 95%CI: -0.134 to -0.000; P = 0.049). Using RCS explored potential nonlinear relationships between MHR and telomere length, revealing no nonlinear relationship between the two (P = 0.102).ConclusionsThis study suggests a negative correlation between MHR levels and telomere length in American adults. More comprehensive research is needed to confirm these findings in the future.

Leukocytes telomere length as a biomarker of adverse drug reactions induced by Osimertinib in advanced non-small cell lung cancer

This study aimed to measure relative telomere length (RTL) in blood leukocytes of advanced-stage NSCLC patients either with or without Osimertinib-induced ADRs and determine whether RTL could serve as a biomarker of Osimertinib-induced ADRs. Blood leukocytes RTL were measured in 63 advanced-stage NSCLC patients and 62 age-matched healthy controls using real-time polymerase chain reaction. In patients with advanced-stage NSCLC, RTL was significantly shorter than that in healthy controls (P < 0.001). Compared to patients without ADRs and those with mild/moderate ADRs, patients with severe ADRs exhibited significantly decreased RTL (P < 0.001, P < 0.001, respectively). ROC curve analysis uncovered a diagnostic value of RTL as a biomarker of Osimertinib-induced ADRs (AUC = 1.000, P < 0.001). Kaplan-Meier analysis revealed a significant association between shorter RTL and increased cumulative incidence of Osimertinib-induced ADRs in patients with advanced-stage NSCLC (P < 0.001). Shorter RTL in blood leukocytes would reflect the occurrence of Osimertinib-induced ADRs and might emerge as a promising biomarker for identifying advanced-stage NSCLC patients who are at risk of experiencing Osimertinib-induced ADRs, particularly those with severe ADRs.

TGF-β superfamily-induced transcriptional activation pathways establish the RAD52-dependent ALT machinery during malignant transformation of MPNSTs

To study telomere maintenance mechanism (TMM) activation during malignant transformation, we compared neurofibroma (NF) and malignant peripheral nerve sheath tumor (MPNST) in the same patient with type-1 neurofibromatosis (NF1), a total of 20 NF-MPNST pairs in 20 NF1 patients. These comparisons minimized genetic bias and contrasted only changes associated with malignant transformation, while subtracting changes that developed upon the transformation of normal cells to the benign tumor. TGF-β superfamily genes were found to activate the PAX and SOX transcription factors, leading to TMM activation. BMPER activates PAX6 through BMP2 and PAX7 through BMP4; BMP15 activates SOX14; and INHBC activates PAX9 and SOX14. The activated PAX and SOX genes sequentially establish the core architecture of the RAD52-dependent alternative lengthening of telomeres (ALT). Specifically, PAX7 activates the recombinase (RAD52) and a negative regulator (SLX4IP). PAX6 and SOX14 activate positive regulators (BLM and BRCA2, respectively). PAX9 and SOX14 activate RAD9B and FEN1, which are responsible for the stability of homologous recombination intermediates and increase, together with RAD52, the telomere length. Telomere elongation achieved by the activation of PAX7 and PAX9 is associated with a poor prognosis. We demonstrated that TGF-β superfamily-induced transcriptional activation pathways activated the RAD52-dependent ALT during malignant transformation of MPNSTs.

Leptin modulates ovarian granulosa cell apoptosis by regulating telomerase activity and telomere length in polycystic ovary syndrome

Leptin (LEP) is implicated in the pathogenesis of polycystic ovary syndrome (PCOS). This study investigates the mechanism of LEP in PCOS. The baseline information of 80 PCOS patients and matched controls was analyzed, with serum and follicular fluid (FF) LEP and LEP receptor (LEPR) levels, telomerase activity, and relative telomere length (TL) measured. The correlation of FF LEP with telomerase activity and TL was analyzed. The viability and apoptosis of KGN cells (the ovarian granulosa cells) treated with gradient LEP were assessed. LEP-LEPR interaction was examined. LEPR, c-MYC, and TERT levels and c-MYC protein expression in the TERT promoter region were determined. Nuclear c-MYC translocation was detected. LEP was upregulated in sera and FF of PCOS patients. FF LEP positively-correlated with telomerase activity and TL. Low-concentration LEP facilitated KGN cell proliferation and high-concentration LEP dose-dependently suppressed cell proliferation, promoted apoptosis, upregulated LEPR and increased telomerase activity and relative TL. LEP-LEPR interaction upregulated c-MYC and facilitated its nuclear accumulation. c-MYC enrichment in the TERT promoter region upregulated TERT, altering telomerase activity and TL and inducing cell apoptosis. Briefly, LEP/LEPR activate c-MYC, modulate TERT expression, and increase telomerase activity and TL, thus inducing ovarian granulosa cell apoptosis and participating in PCOS.

Ionizing radiation has negligible effects on the age, telomere length and corticosterone levels of Chornobyl tree frogs.

The accident that occurred at the Chornobyl nuclear power plant (Ukraine, 1986) contaminated a large extension of territory after the deposition of radioactive material. It is still under debate whether the chronic exposure to the radiation levels currently present in the area has long-term effects on organisms, such as decreases in longevity. Here, we investigate whether current levels of radiation in Chornobyl negatively impact the age of the Eastern tree frog Hyla orientalis. We also explore whether radiation induces changes in an ageing marker, telomere length or the stress hormone corticosterone. We found no effect of total individual absorbed radiation (including both external and internal exposure) on frog age (n = 197 individuals sampled in 3 consecutive years). We also did not find any relationship between individual absorbed radiation and telomere length, nor between individual absorbed radiation and corticosterone levels. Our results suggest that radiation levels currently experienced by Chornobyl tree frogs may not be high enough to cause severe chronic damage to semi-aquatic vertebrates such as this species. This is the first study addressing age and stress hormones in Chornobyl wildlife, and thus future research will confirm if these results can be extended to other taxa.

Telomere length and cognitive changes in 7,877 older UK adults of European ancestry

Telomere length and cognitive changes in 7,877 older UK adults of European ancestry

Telomere length across the spectrum of metabolic health – an analysis from the LIPIDOGEN2015 study

IntroductionBackground: Telomere length is a cellular aging marker and correlates with various cardiovascular disease (CVD) risk factors. The current study assessed the association between obesity, metabolic syndrome (MetS), and telomere length.Material and methodsMaterial and methods: The LIPIDOGRAM&amp;LIPIDOGEN2015 study was conducted in primary care in 2015-2016. Recruited patients to the LIPIDOGEN2015 cohort (n=1788) were a random subset of patients of the LIPIDOGRAM2015 (n=13,724) study. For the aims of this analysis, the recruited patients were divided into four groups based on the presence of MetS: healthy slim (HS), metabolically healthy obese (MHO), non-obese with MetS (NOMS), and metabolically unhealthy obese (MUO). Relative telomere length (RTL) was measured using quantitative polymerase chain reaction (qPCR).ResultsResults: 1516 patients (85%; females - 59.7%, mean age- 50.3 years) were included for final analyses. An increase in body mass index (BMI), waist circumference, prevalence of diabetes mellitus, hypertension, dyslipidemia, and history of myocardial infarction moving from HS to MUO were observed. MUO group exhibited the highest triglycerides and lowest high-density lipoprotein (HDL-C) levels. Univariable regression analyses indicated that NOMS (p=0.038) and MUO (p=0.003) were associated with significantly decreased RTL. After adjustment for age, gender, education, smoking, place of residence, and myocardial infarction, the association was no longer statistically significant.ConclusionsConclusions: Despite the lack of statistical significance in the multivariate analysis, the univariate results suggest that both MUO and NOMS phenotypes contribute to the shortening of telomere length. These results may also indicate that MetS, irrespectively on obesity occurrence, is responsible for the shortened lifespan.

Molecular signature underlying (R)-ketamine rapid antidepressant response on anhedonic-like behavior induced by sustained exposure to stress

Anhedonia induced by sustained stress exposure is a hallmark symptom of major depressive disorder (MDD) and in rodents, it can be accessed through the sucrose preference test (SPT). (R)-ketamine is a fast-acting antidepressant with less detrimental side effects and abuse liability compared to racemic ketamine. The present study combined high-throughput proteomics and network analysis to identify molecular mechanisms involved in chronic variable stress (CVS)-induced anhedonia and promising targets underlying (R)-ketamine rapid antidepressant response. Male Wistar rats were subjected to CVS for five weeks. Based on the SPT, animals were clustered into resilient or anhedonic-like (ANH) groups. ANH rats received a single dose of saline or (R)-ketamine (20 mg/kg, i.p.), which was proceeded by treatment response evaluation. After prefrontal cortex collection, proteomic analysis was performed to uncover the differentially expressed proteins (DEPs) related to both anhedonic-like behavior and pharmacological response. The behavioral assessment showed that the ANH animals had a significant decrease in SPT, and that (R)-ketamine responders showed a reversal of anhedonic-like behavior. On a molecular level, anhedonia-like behavior was associated with the downregulation of Neuronal Pentraxin Receptor (Nptxr) and Galectin−1 (Gal-1). These data reinforce a disruption in the inflammatory response, neurotransmitter receptor activity, and glutamatergic synapses in chronic stress-induced anhedonia. (R)-ketamine response-associated DEPs included novel potential targets involved in the modulation of oxidative stress, energetic metabolism, synaptogenesis, dendritic arborization, neuroinflammation, gene expression, and telomere length, converging to biological themes extensively documented in MDD physiopathology. Our data provide valuable insights into the molecular mechanisms underlying the response to (R)-ketamine and highlight these pathways as potential therapeutic targets for anhedonia. By addressing proteins involved in oxidative stress, energy metabolism, synaptogenesis, dendritic arborization, neuroinflammation, gene expression, and telomere length, we can target multiple key factors involved in the pathophysiology of MDD. Modulating these proteins could open avenues for novel therapeutic strategies and deepen our understanding of anhedonia, offering hope for improved outcomes in individuals facing this challenging condition. However, additional studies will be essential to validate these findings and further explore their therapeutic implications.

Causal linkage of Graves’ disease with aging: Mendelian randomization analysis of telomere length and age-related phenotypes

BackgroundAging is an irreversible progressive decline in physical function. Graves’ disease (GD) is a common cause of hyperthyroidism and is characterized by elevated levels of the thyroid hormone (TH). High TH levels are associated with aging and a shortened lifespan. The causal relationship between GD and aging has yet to be investigated.MethodsWe used genome-wide association study (GWAS) datasets and Mendelian randomization (MR) analysis to explore the causal link between GD and aging. To assess the statistical power of instrumental variables (IVs), F-statistics and R2 were used. MR analysis was conducted using inverse-variance weighting (IVW), MR-Egger, weighted median, and weighted mode. The odds ratio (OR) and 95% CI were calculated to estimate the relative risk of GD to the outcomes. The Cochran Q test, I2, MR-PRESSO test, and MR-Egger regression intercept were calculated using statistical and leave-one-out analyses to test the heterogeneity, horizontal pleiotropy, and stability of the IVs on the outcomes.ResultsF-statistics of the five IVs were greater than 10, and the R2 values ranged from 0.033 to 0.156 (R2 > 0.01). According to the results of the IVW analysis, GD had no causal effect on facial aging (p = 0.189), age-related macular degeneration (p = 0.346), and Alzheimer’s disease (p = 0.479). There was a causal effect of GD on the remaining outcomes: telomere length (TL) (OR = 0.982; 95%CI:0.969–0.994; p = 0.004), senile cataract (OR = 1.031; 95%CI:1.002–1.060; p = 0.033), age-related hearing impairment (OR = 1.009; 95%CI:1.004–1.014; p = 0.001), chronic obstructive pulmonary disease (COPD) (OR = 1.055; 95%CI:1.008–1.103; p = 0.020), and sarcopenia (OR = 1.027; 95%CI:1.009–1.046; p = 0.004).ConclusionsGD accelerates the occurrence of age-related phenotypes including TL, senile cataracts, age-related hearing impairment, COPD, and sarcopenia. In contrast, there are no causal linkages between GD and facial aging, age-related macular degeneration, or Alzheimer’s disease. Further experimental studies could be conducted to elucidate the mechanisms by which GD facilitates aging, which could help slow down the progress of aging.

Substantial elevation of telomeric oxidized bases in childhood autism

BackgroundThe underlying molecular mechanisms responsible for the etiology of autism and its sex-biased prevalence remain largely elusive. We have previously shown that children with non-syndromic low-functioning idiopathic autism exhibit a sexually dimorphic pattern of relative telomere length (RTL), with autistic male children having significantly shorter RTL than autistic female children, healthy controls, and paired siblings. By contrast, a number of autistic girls had longer RTLs than healthy controls. Here, we investigated levels of telomeric oxidized base (TelOB) lesions among the same study subjects and groups. MethodsEmploying a quantitative PCR (qPCR)-based method, which combines DNA digestion targeting oxidized bases and telomere measurement, TelOB lesions were measured using genomic DNA extracted from saliva samples collected from 24 children (14 male and 10 female) with autism, 10 paired siblings, and 24 sex, age, and location-matched typically-developing controls. ResultsOur findings show that both male and female autistic children exhibit substantially higher TelOB lesions at their telomeres than healthy controls and paired siblings. Interestingly, these elevated levels of TelOBs show a direct correlation with RTL values in autistic children but not in healthy controls. However, TelOB levels do not show any association with age either in the autistic children or the healthy control group. ConclusionsOur findings open a fresh angle into autism spectrum disorders (ASD), raise new questions, and lay the foundation for further research into telomere biology and underlying molecular mechanisms involved in ASD. TelOB levels are likely set during early development and may serve as biomarkers for childhood autism.

Parental age at birth, telomere length, and autism spectrum disorders in the UK Biobank cohort.

Older parental age at birth is associated with increased risk of autism spectrum disorders (ASD) in offspring. Independently, shorter telomere length (TL) has also been shown to be associated with ASD in children. However, older paternal age at birth, with or without controlling for maternal age, has been associated with longer TL, a seemingly contradictory finding. Here, we conducted a retrospective cohort study among participants in the UK Biobank to disentangle associations between leukocyte TL and ASD status in adults, and the potential moderation by parental age on adult offspring's TL. Participants with ASD diagnosis (N = 87) with a mean age of 46.0 (SD 4.4) years were matched to participants without ASD diagnosis (N = 870) based on age, sex, ethnicity, education, household income, and assessment center. No statistically significant differences were seen in TL between participants with and without ASD when parental age at birth was not considered. However, there was a significant interaction between ASD diagnostic status and parental age on participants' TL, such that older paternal or maternal age at birth was more strongly associated with longer TL in participants with ASD. This study suggests that the shortened TL observed in children with ASD in previous research may partially depend on parental age at birth. Future studies tracking TL attrition before ASD diagnosis are warranted to depict temporal associations and the interacting effects of parental age at birth and ASD status on TL across the lifespan.

Telomere Length and Biological Aging: The Role of Strength Training in 4814 US Men and Women

Telomere length is an index of cellular aging. Healthy lifestyles are associated with reduced oxidative stress and longer telomeres, whereas unhealthy behaviors are related to shorter telomeres and greater biological aging. This investigation was designed to determine if strength training accounted for differences in telomere length in a random sample of 4814 US adults. Data from the National Health and Nutrition Examination Survey (NHANES) were employed to answer the research questions using a cross-sectional design. Time spent strength training was calculated by multiplying days of strength training per week by minutes per session. Participation in other forms of physical activity was also calculated based on reported involvement in 47 other activities. Weighted multiple regression and partial correlation were used to calculate the mean differences in telomere length across levels of strength training, adjusting for differences in potential confounders. With the demographic covariates controlled, strength training and telomere length were linearly related (F = 14.7, p = 0.0006). Likewise, after adjusting for all the covariates, the linear association remained strong and significant (F = 14.7, p = 0.0006). In this national sample, 90 min per week of strength training was associated with 3.9 years less biological aging, on average. Regular strength training was strongly related to longer telomeres and less biological aging in 4814 US adults.

Mapping the evolving trend of research on leukocyte telomere length: a text-mining study

BackgroundSubstantial evidence indicates that measuring leukocyte telomere length (LTL) is a useful tool that may be considered as a valuable biomarker of individual biological age, correlating with numerous chronic disorders. However, to date, there has been a lack of in-depth understanding regarding the current landscape and forthcoming developments in the LTL field. Therefore, this study aimed to utilize bibliometric methods to summarize the knowledge structure, current focus, and emerging directions in this field.MethodScientific publications on LTL spanning the period from 2000 to 2022 were acquired from the Web of Science Core Collection database. Several bibliometric tools including CiteSpace, VOSviewer, and an online website were utilized for bibliometric analysis. The primary evaluations encompassed investigating the major contributors and their collaborative relationships among countries/regions, institutions, and authors, conducting co-citation analyses of authors, journals, as well as reference, examining reference bursts, as well as performing co-occurrence analyses of keywords.ResultsThere are 1818 papers with 66,668 citations identified. Both the annual publication and citation counts on LTL exhibited significant upward trends. The United States emerged as the most prominent contributor, as evidenced by the greatest volume of papers and the highest H-index value. University of California San Francisco and Aviv A were identified as the most productive institution and author in this domain, respectively. Reference analysis revealed that longitudinal study and mendelian randomization study are the most concerned research method in this field recently. Keywords analysis showed that the most concerned diseases in LTL fields were aging, inflammation, cardiovascular diseases, endocrine diseases, neurological and psychiatric diseases, and cancers. In addition, the following research directions such as “COPD”, “mendelian randomization”, “adiposity”, “colorectal cancer”, “National Health and Nutrition Examination Survey (NHNES)”, “telomerase reverse transcriptase”, “pregnancy” have garnered increasing attention in recent times and hold the potential to evolve into research foci in the foreseeable future.ConclusionThis is the first bibliometric study that provides comprehensive overview of LTL research. The findings of this study could become valuable references for investigators to explore and address the current and emerging challenges in LTL research.

Telomere length across spectrum of metabolic health

Abstract Introduction Telomere length is a marker of cellular aging and is correlated with various cardiovascular risk factors. Aim To assess the association between obesity, metabolic syndrome (MetS) and telomere length. Methods The LIPIDOGEN study was carried out in the primary care 2015. Patients recruited to LIPIDOGEN cohort (n=1788) were a random subset of patients from LIPIDOGRAM 2015 (n=13,724) study. Patients for LIPIDOGRAM2015/LIPIDOGEN study were recruited in all 16 administrative regions in Poland and physicians were proportionally distributed to the number of inhabitants in each administrative region. Each patient was asked to fill the questionnaire on risk factors, chronic diseases, treatments and lifestyle and also had saliva secured for DNA analyses. Recruited patients were divided into four groups based on the presence of MetS: 1) HS – healthy slim 2) MHO – metabolically healthy obese 3) NOMS – Non-obese with MetS 4) MUO – metabolically unhealthy obese. MetS was diagnosed basing on Joint Interim Statement 2009 criteria. Relative telomere length (rTL) was measured using quantitative polymerase chain reaction. Results DNA quality was sufficient for further analyses in 1606 patients. After removing of outliers, 1342 patients (Females - 59.3%, mean age- 50.2 years) were included for further analyses (HS-488, MHO-180, NOMS-165, MUO-509). Increase in BMI, waist circumference, frequency of diabetes mellitus, hypertension, dyslipidemia and history of myocardial infarction moving from HS to MUO was observed. (Table 1.). MUO group exhibited the highest triglycerides and lowest HDL-C levels. RTL length, an indicator of cellular aging, was inversely correlated with metabolic health, being shortest in the NOMS and MUO groups, which may indicate a link between metabolic health and accelerated biological aging. Conclusions Telomere length is shorter in patients with obesity as compared to lean patients even without the presence of MetS. Telomere length in patients with MetS, regardless of concomitant obesity, is shorter than in patients without MetS. Figure 1. Telomere length across metabolic health categories. Table 1. Clinical characteristics of the study participants.Figure. 1.Table. 1.

Race/Ethnicity, Education, and All-Cause Mortality in US Adults: Mediation by Telomere Length

Abstract Background Racial/ethnic inequities in mortality risk are pervasive in the United States even after controlling for socioeconomic status indicators such as educational attainment. Although the mechanisms underlying these inequities remain unclear, telomere length (TL) has emerged as a potential mediator. We aimed to investigate the joint association of race/ethnicity and education with all-cause mortality risk, and the contribution of TL to this relationship. Methods We used data from the U.S. National Health and Nutrition Examination Survey, 1999 to 2002, and 2019 Linked Mortality File (n = 6,526 non-institutionalized adults aged 25 years or older, including 2,166 deaths), a retrospective cohort study with a follow-up period to December 31, 2019. Cox proportional hazards regression and causal mediation analysis were used to address these aims. We reported hazard ratios (HR) and 95 % confidence intervals (CI). Furthermore, for the mediation analysis, we reported the total, direct, and indirect effects measured as HR and 95 % CI. Results After adjusting for age and sex, among White individuals, those with less than a high school education had a 2.26 times higher (95% CI: 1.93, 2.65) rate of all-cause mortality compared to those with some college or higher education. When compared with White adults with at least a college degree, Black adults with at least a college degree had a 1.38 higher rate of dying (95% CI: 1.04, 1.84). There was no significant joint association of race/ethnicity and education on all-cause mortality in Mexican Americans. In the mediation analysis, TL did not significantly contribute to the joint association of race/ethnicity and education with all-cause mortality risk. Discussion These findings underscore the need for a better understanding of the joint relationship of race/ethnicity and education on mortality risk inequities and their potential mechanisms to improve population health ultimately. Key messages • Lower educational attainment was associated with higher mortality rates among White individuals, disparities persisted among the Black population, despite higher education levels. • Our analysis did not find a significant mediation effect of telomere length on the joint effect of race/ethnicity and education-mortality relationship.

Association of telomeres length with cardiovascular risk factors and arterial stiffness

Abstract Background Leukocyte telomere length (LTL) has been explored as a marker of biological aging, with connections established to age-related diseases like atherosclerosis. Studies have particularly associated telomeres with conditions such as peripheral vascular disease, coronary heart disease, and cardiovascular mortality. Methods In this cross-sectional analysis we enrolled individuals from "Corinthia" study which was conducted in the homonym region in Greece. We measured LTL in individuals to obtain comparative metrics on the prevalence of cardiovascular risk factors as well as arterial stiffness. Carotid-femoral pulse wave velocity (cfPWV) was used to evaluate arterial stiffness. Results Our analysis included 419 individuals aged 62.4 ± 11.8 years with a median LTL at 6.78 (IQR: 5.08-8.72) bp. Using the median LTL as a cutoff, the cohort was divided into two groups, Group A: 208 patients with low LTL, Group B: 211 patients with high LTL. Group A exhibited a significantly higher proportion of males (52.4% vs. 34.1%, p &amp;lt; 0.01), higher body mass index (BMI) (29.3 ± 4.7 kg/m2 vs. 28.5 ± 4.4 kg/m2, p &amp;lt;0.05), and a higher prevalence of hypertension (78.8% vs. 67.8%, p = 0.01) and dyslipidemia (51% vs. 38.9%, p = 0.014). No significant difference was observed regarding the prevalence of diabetes mellitus, smoking habits, and established cardiovascular disease. In the analysis of the whole cohort, cfPWV was found significant higher in Group A (9.61 ± 3.46 m/s vs. 8.38 ± 2.49 m/s, p &amp;lt;0.01) compared to group B (Figure, Panel A). This association remained significant (β = -0.096, p = 0.038), even after adjustment for confounders in the multivariate regression analysis. Finally, a statistically significant negative correlation between LTL and cfPWV was observed (Figure, Panel B). Conclusion LTL plays a pivotal role in cardiovascular health, and lower LTL is associated with impaired cfPWV values and a heightened prevalence of obesity, hypertension, and dyslipidemia.Asociation of LTL with cfPWV values.

Association of leukocyte telomere length and the risk of disease severity and metabolic comorbidities in Arab patients with psoriasis.

Several studies have related shortened leukocyte telomere length (LTL) with age-related diseases and worse prognosis. Telomere length attrition has recently been associated with inflammatory diseases, including psoriasis. However, no study has demonstrated an association between LTL and the risk of disease severity and metabolic comorbidities in Arab patients with psoriasis (Ps). 68 Ps and 42 normal controls (NC) were included. LTL and oxidative damage were determined by quantitative (q) PCR. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression. Statistical differences between the groups were determined using 2 and t-tests. Patients with psoriasis had significantly shorter LTL (P= 0.032) and higher oxidative damage (P= 0.015) than those without psoriasis. Patients with moderate-to-severe index (P= 0.03) and metabolic comorbidity showed significantly shorter LTL (P= 0.003) compared to patients with mild index and without metabolic comorbidity, respectively. Patients with short LTL (≤ 0.9) were correlated with higher risk of moderate-to-severe conditions (OR= 6.98, 95% CI= 2.3-20.8, P= 0.001) and metabolic comorbidities (OR= 2.89, 95% CI= 1.02- 8.2, P= 0.04). LTL shortening may be a consequence of increased oxidative damage, and is related to the risk of severe psoriasis and metabolic comorbidities. Therefore, LTL may be a good candidate biomarker for predicting the risk of poor prognosis in patients with psoriasis.