Telomere Length Measurement in Human Tissue Sections by Quantitative Fluorescence In Situ Hybridization (Q-FISH).

Telomeres in most somatic cells shorten with each cell division, and critically short telomeres lead to cellular dysfunction, cell cycle arrest, and senescence. Thus, telomere shortening is an important hallmark of human cellular senescence. Quantitative fluorescence in situ hybridization (Q-FISH) using formalin-fixed paraffin-embedded (FFPE) tissue sections allows the estimation of telomere lengths in individual cells in histological sections. In our Q-FISH method, fluorescently labelled peptide nucleic acid (PNA) probes are hybridized to telomeric and centromeric sequences in FFPE human tissue sections, and relative telomere lengths (telomere signal intensities relative to centromere signal intensities) are measured. This chapter describes our Q-FISH protocols for assessing relative telomere lengths in FFPE human tissue sections.

Shorter Leukocyte Telomere Length Is Associated with Increased Major Adverse Cardiovascular Events or Mortality in Patients with Essential Hypertension.

The association between leukocyte telomere length (LTL) alteration and major adverse cardiovascular events (MACE) or mortality in patients with hypertension is still unclear. 20,034 patients with essential hypertension were enrolled from UK biobank. Multivariable COX regression models were performed to assess the association. LTL was shorter in hypertensive patients with MACE compared to those without MACE. Hypertensive patients in the lowest LTL quartile were at higher risk to develop MACE (adjusted HR 1.15 [95% CI 1.02-1.29], vs top LTL quartile, p-trend = 0.03). Similarly, shorter LTL was related with increased mortality (adjusted HR 1.18[95% CI 1.06-1.3], lowest vs top LTL quartile, p-trend < 0.001). This investigation demonstrated that shorter LTL is associated with increased risk of MACE or mortality in patients with essential hypertension, which indicates that LTL may be a potential predictor of prognosis or underlying therapeutic target for hypertension.

Shorter Telomere Length is Associated with Food Insecurity in Older People: A Cross-Sectional Study.

BACKGROUND: Telomere length has been investigated as a biomarker of biological aging and is associated with several diseases, lifestyle, and socioeconomic factors. OBJECTIVE: This study aimed to verify whether food insecurity is associated with shorter telomere length in older people. METHODS: This is a cross-sectional study carried out in a municipality in the interior of Brazil, with a sample of 440 older people from the community. For telomere length analysis, a blood sample was obtained from each participant, followed by real-time qPCR, and sociodemographic and health information was collected through interviews. Food security/insecurity was measured using the reduced version of the Brazilian Food Insecurity Scale. Descriptive analysis and multiple logistic regression were performed to analyze the factors associated with shorter telomere length, adopting a significance level of 5%. RESULTS: We found that food insecurity was significantly associated with shorter telomere length, regardless of age group, skin color, tabagism, physical activity, milk and dairy consumption, living arrangement, and basic activities of daily life. CONCLUSION: The findings show the importance of ensuring full access to adequate nutrition for the older population, who are physiologically and socially vulnerable.

Telomere Length and Telomerase Activity as Potential Biomarkers for Gastrointestinal Cancer.

Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromosome ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering insights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers.

The Association between Leucocyte Telomere Length and Survival Outcomes in Patients with Cardiovascular Disease.

Background: We explore the association between leucocyte telomere length (LTL) and all-cause and cardiovascular disease (CVD)-specific death in CVD patients. Methods: We acquired 1599 CVD patients from a nationally representative US population survey for this study. We applied Kaplan-Meier curves, adjusted weighted Cox regression models, and restricted cubic spline to investigate the association between LTL and all-cause death. Additionally, we employed competing risk regression to assess the impact of LTL on cardiovascular-specific death, setting non-cardiovascular death as a competing event. Results: The overall mortality rate was 31.0% after a median follow-up of 13.9 years. Patients with shorter LTL exhibited a higher risk of all-cause death, with an adjusted hazard ratio (HR) of 1.25 (95% confidence interval (CI): 1.05-1.48). Restricted cubic spline illustrated a linear dose-response relationship. In gender-specific analyses, female patients with shorter LTL showed a higher risk of death (weighted HR, 1.79; 95% CI, 1.29-2.48), whereas this association was not observed in males (weighted HR, 0.90; 95% CI, 0.61-1.32). The Fine-Gray competing risk model revealed no significant relationship between LTL and cardiovascular-specific mortality but a significant association with non-cardiovascular death (adjusted HR, 1.24; 95% CI, 1.02-1.51). Conclusions: LTL is inversely associated with all-cause death in female CVD patients. The significant correlation between reduced LTL and increased all-cause mortality emphasizes LTL as a potential marker for tertiary prevention against cardiovascular disease.

The negative association between sodium-driven nutrient pattern and telomere length: the chain mediating role of diastolic pressure and waist circumference.

BACKGROUND: Numerous single nutrients have been suggested to be linked with leukocyte telomere length (LTL). However, data on nutrient patterns (NPs), particularly in Chinese population, are scarce. This study aimed to examine the relationship between nutrient-based dietary patterns and LTL, and the potential role of metabolic factors. METHODS: Dietary data was obtained via 24-hour food recalls, and principal component analysis (PCA) was used to identify NPs. LTL was assessed using a real-time PCR assay. Multiple linear regression was conducted to determine the association between NPs and LTL. The potential role of metabolism among them was analyzed using mediation models. RESULTS: A total of 779 individuals from northern China were included in this cross-sectional analysis. Five main nutrient patterns were identified. Adjusted linear regression showed that the "high sodium" pattern was inversely associated with LTL (B=-0.481(-0.549, -0.413), P < 0.05). The "high vitamin E-fat" pattern exhibited a positive correlation (B = 0.099(0.029, 0.170), P < 0.05), whereas the "high vitamin A-vitamin B2" pattern was negatively correlated with LTL (B=-0.120(-0.183, -0.057), P < 0.05), respectively. No significant associations were observed for the remaining nutrient patterns. The mediation model demonstrated that diastolic blood pressure and waist circumference could individually and collectively mediate the negative impact of the "high sodium" pattern on LTL (BDBP=-0.0173(-0.0333, -0.0041), BWC=-0.0075(-0.0186, -0.0004), Bjoint=-0.0033 (-0.0072, -0.0006), all P < 0.05). Moreover, glycosylated hemoglobin and non-high-density lipoprotein cholesterol mediate the relationship between the "high vitamin E-fat" pattern and LTL (BHbA1c=0.0170(0.0010,0.0347), Bnon-HDL-C= 0.0335 (0.0067, 0.0626), all P < 0.05), respectively. CONCLUSIONS: The "high sodium" and "high vitamin E-fat" nutrient patterns demonstrated negative and positive associations with LTL and metabolic indicators may play complex mediating roles in these relationships.

An in-silico approach to the dynamics of proliferation potential in stem cells and the study of different therapies in cases of ovarian dysfunction.

A discrete mathematical model based on ordinary differential equations and the associated continuous model formed by a partial differential equation, which simulate the generational and temporal evolution of a stem cell population, are proposed. The model parameters are the maximum proliferation potential and the rates of mitosis, death events and telomerase activity. The mean proliferation potential at each point in time is suggested as an indicator of population aging. The model is applied on hematopoietic stem cells (HSCs), with different telomerase activity rates, in a range of variation of maximum proliferation potential in healthy individuals, to study the temporal evolution of aging. HSCs express telomerase, however not at levels that are sufficient for maintaining constant telomere length with aging [1,2]. Women with primary ovarian insufficiency (POI) are known to have low telomerase activity in granulosa cells and peripheral blood mononuclear cells [3]. Extrapolating this to hematopoietic stem cells, the mathematical model shows the differences in proliferation potential of the cell populations when telomerase expression is activated using sexual steroids, though the endogenous promoter or with gene therapy using exogenous, stronger promoters within the adeno-associated virus. In the first case, proliferation potential of cells from POI condition increases, but when adeno-associated viruses are used, the proliferation potential reaches the levels of healthy cell populations.

The association of telomere length with body mass index and immunological factors differs according to physical activity practice among children and adolescents.

BACKGROUND: This study aims to verify the relationship between screen and sleep time, body mass index (BMI) and immunological factors with telomere length according to leisure-time physical activity (PA) in children and adolescents. METHODS: A cross-sectional study involving a sample of 476 schoolchildren of both sexes, aged seven to 17 years, from a community in southern Brazil. Behavioral variables (PA, sleep time, and screen time) were self-reported using a questionnaire. PA was classified as inactive and any PA (doing some physical activity). The associations of screen time, sleep time, BMI, and immunologic factors with telomere length were tested using multiple linear regression models, with the sample divided according to the schoolchildren's leisure-time physical activity practices. RESULTS: An inverse association between BMI and telomere length (ß: -0.239; 95% CI: -0.468; -0.010) and a direct association of leukocytes (ß: 0.151; 95% CI: 0.029; 0.278) and neutrophils (ß: 0.131; 95% CI: 0.008; 0.254) with telomeres were found in the inactive students. No association was found between screen time and sleep time and telomeres. No association was found among students who engaged in any PA. CONCLUSION: The associations between telomeres, BMI, and immunologic factors were found only in inactive students. These results suggest that the association between BMI and immunological factors and telomere length may be influenced by physical activity.

Does Adulthood Socioeconomic Status Predict Subsequent Telomere Length in Racially and Ethnically Diverse Women?

Background: Telomere length is a critical biomarker of cellular aging and overall health. While childhood socioeconomic status (SES) indicators such as education and poverty can have long-lasting effects on biological aging, research has shown contradictory results regarding the impact of adulthood SES on future telomere length, particularly in racially and ethnically diverse individuals. This study investigates the effects of baseline adulthood SES indicators such as education and poverty on telomere length nine years later in women, using data from the Future of Families and Child Wellbeing Study (FFCWS). Methods: We analyzed data from the FFCWS, a longitudinal cohort study. The sample included baseline adulthood SES and follow-up telomere length measure of women (n = 2,421) with varying socioeconomic conditions. Telomere length was measured from saliva samples nine years after the baseline measure of adulthood SES. Education, poverty, and marital status at baseline were assessed. Multivariate linear regression models were used to examine the association between adulthood SES indicators at baseline and future telomere length, controlling for potential confounders. Results: From the total 2,421 women, 675 were Latino White, 1,158 were non-Latino Black, and 588 were non-Latino White. Our findings indicate that for non-Latino White women poverty at certain level, and childbirth weight, and for non-Latino Black maternal age were predictors of telomere lengths nine years later. Conclusion: Poverty at a specific level, maternal age and childbirth weight serve as predictors of telomere lengths nine years later in some women. These findings underscore the importance of socioeconomic factors and early-life influences in understanding telomere dynamics and aging processes among women from varied racial and ethnic backgrounds.

The relationship between leukocyte telomere length and risk of depression and anxiety: Evidence from UK Biobank.

BACKGROUND: Telomere length is a cellular aging marker implicated in various health outcomes. A growing body of evidence suggests a link between leukocyte telomere length (LTL) and mental health outcomes. However, there have been no studies focused on the relationship between LTL and the future risk of depression and anxiety. This study aimed to investigate the associations between LTL and depression/anxiety, examining both cross-sectional prevalence and prospective incidence. METHODS: Data from 364,331 UK Biobank participants were analyzed. LTL was measured at baseline, and mental health status was assessed through hospital records and online surveys. Logistic regression and Cox proportional hazards models were employed for cross-sectional and prospective analyses with appropriate adjustment, respectively. RESULTS: The mean (SD) age of the subjects was 57.03 (13.34) years and follow-up duration was 8.80 (5.39) years. Cross-sectionally, shorter LTL was associated with increased odds of depression (OR: 1.401, 95 % CI: 1.291-1.521) and anxiety (1.347 (1.198-1.515)) at baseline, which remained significant after adjustment. Among those free of depression/anxiety at baseline, baseline shorter LTL was associated with a higher risk of incident depression (HR: 1.615, 95 % CI: 1.447-1.803) and anxiety (1.430 (1.293-1.581)) during follow-up period. These associations remained robust after adjusting for various covariates. CONCLUSIONS: Our findings indicated an association between shorter telomeres and an increased risk of prevalent depression/anxiety and shorter telomeres precede the onset of these mental health conditions. Considering the potential clinical implications, our study underscores the relevance of LTL as a predictive tool for identifying individuals at risk of developing depression and anxiety.

Peripartum depression symptom trajectories, telomere length and genotype, and adverse childhood experiences.

BACKGROUND: As a biological marker for cellular senescence, telomere length (TL) has been linked to a variety of psychiatric disorders and adverse childhood experiences (ACE), though only preliminarily to peripartum depression (PPD). The present study sought to examine the association between TL and PPD, assessing the moderating role of ACE and genetic polymorphic variations related with the telomere machinery. METHODS: Adversity was self-reported, likewise were depressive symptoms evaluated at pregnancy week 17 and 32, as well as six-weeks and six-months postpartum. TL was assessed by use of qPCR in blood samples collected during delivery from females with antenatal depression resolving postpartum, females with depression persisting to postpartum, and healthy controls. Twenty haplotype-tagging Single Nucleotide Polymorphisms in the Telomerase Reverse Transcriptase (TERT) and three in the Telomerase RNA Component (TERC) genes were genotyped. RESULTS: TL was negatively correlated with severity of PPD symptoms at pregnancy week 32 and postpartum week 6. PPD was associated with shorter TL. Lastly, ACE, but not the TERT/TERC genotype, moderated the TL-trajectory association; with increasing ACE, individuals with persistent PPD symptoms had shorter TL, whereas the opposite pattern (longer TL) was observed in the controls. CONCLUSIONS: The findings contribute to further understanding of PPD underpinnings, suggesting a negative relationship with TL.

The fetal origins of metabolic health: exploring the association between newborn biological age and metabolism hormones in childhood.

BACKGROUND: Telomere length (TL), mitochondrial DNA copy number (mtDNAcn), and DNA methylation age (DNAmAge) are common aging biomarkers. However, research on the associations between these three markers at birth and subsequent metabolic status was limited. This study aimed to evaluate the association between TL, mtDNAcn, and DNAmAge in newborns and the variation in metabolic hormones of children at 3 years old. METHODS: This research involved 895 mother-child pairs from a birth cohort in China, with TL and mtDNAcn measured using quantitative real-time PCR, DNA methylation (DNAm) assessed using Infinium MethylationEPIC Beadchip, and DNAm age (DNAmAge) determined using Horvath's epigenetic clock. Insulin and leptin levels were measured via electrochemiluminescence assay. Multivariable adjusted linear regression and restricted cubic spline (RCS) analysis were utilized to examine the association between aging markers and metabolic hormones. RESULTS: The linear regression analysis indicated the percentage change of metabolism hormones for per doubling of aging biomarkers alterations and found significant associations between DNAmAge and insulin levels (adjusted percent change (95% CI), - 13.22 (- 23.21 to - 1.94)), TL and leptin levels (adjusted percent change (95% CI), 15.32 (1.32 to 31.24)), and mtDNAcn and leptin levels (adjusted percent change (95% CI), - 14.13 (- 21.59 to - 5.95)). The RCS analysis revealed significant non-linear associations between TL (Ln transformed) and insulin (Ln transformed) (P = 0.024 for nonlinearity), as well as DNAmAge (Ln transformed) and leptin (Ln transformed) (P = 0.043 for nonlinearity). Specifically, for TL and insulin, a positive association was observed when TL (Ln transformed) was less than - 0.05, which transitioned to an inverse association when TL (Ln transformed) was greater than - 0.05. Regarding DNAmAge and leptin, there was a sharp decline when DNAmAge (Ln transformed) was less than - 1.35, followed by a plateau between - 1.35 and - 0.67 and then a further decline when DNAmAge (Ln transformed) was greater than - 0.67. CONCLUSIONS: In this prospective birth cohort study, variation in metabolic hormones of children at 3 years old was associated with TL, mtDNAcn, and DNAmAge at birth. These findings suggested that TL, mtDNAcn, and DNAmAge might play a role in the biological programming of metabolic health from birth.

Influence of the Bone Marrow Microenvironment on Hematopoietic Stem Cell Behavior Post-Allogeneic Transplantation: Development of Clonal Hematopoiesis and Telomere Dynamics.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential cure for myelodysplastic neoplasms (MDSs) and other hematologic malignancies. This study investigates post-transplantation genetic evolution and telomere dynamics in hematopoietic cells, with a focus on clonal hematopoiesis (CH). We conducted a longitudinal analysis of 21 MDS patients who underwent allo-HSCT between September 2009 and February 2015. Genetic profiles of hematopoietic cells from both recipients and donors were compared at equivalent pre- and post-transplantation time points. Targeted sequencing identified CH-associated mutations, and real-time quantitative PCR measured telomere length. Furthermore, we compared CH incidence between recipients and age-matched controls from the GENIE cohort from routine health checkups. Post-allo-HSCT, 38% of recipients developed somatic mutations not detected before transplantation, indicating de novo CH originating from donor cells. Compared to age-matched healthy controls, recipients showed a significantly higher incidence of CH, suggesting increased susceptibility to genetic changes post-transplant. Telomere length analysis also revealed accelerated shortening in transplanted cells, highlighting the heightened stress and proliferation demands in the new microenvironment. Our findings reveal a notable incidence of donor-derived CH in allo-HSCT recipients, alongside significant telomere attrition. This suggests the potential influence of the marrow microenvironment on genetic and molecular changes in hematopoietic cells.

Telomere length and 4-year changes in cognitive function in an older Mediterranean population at high risk of cardiovascular disease.

BACKGROUND: Cognitive decline, a common process of brain ageing, has been associated with telomere length (TL). Delving into the identification of reliable biomarkers of brain ageing is essential to prevent accelerated cognitive impairment. METHODS: We selected 317 non-smoking 'Prevención con Dieta Mediterránea-Plus' (PREDIMED-Plus) participants (mean age, 65.8 ± 5.0 years) with metabolic syndrome from two trial centres who were following a lifestyle intervention. We measured TL and cognitive function at baseline and after 3 and 4 years of follow-up, respectively. Associations between baseline or 3-year changes in TL and baseline or 4-year changes in cognitive function were analysed using multivariable regression models. RESULTS: Baseline TL was not associated with baseline cognitive performance. Nevertheless, longer baseline TL was associated with improved 4-year changes in the Executive Function domain (ß: 0.29; 95%CI: 0.12 to 0.44; P < 0.001) and the Global Cognitive Function domain (ß: 0.19; 95%CI: 0.05 to 0.34; P = 0.010). Besides, a positive association was found between longer baseline TL and improved 4-year changes in the animal version of the Verbal Fluency Test (ß: 0.33; 95%CI: 0.12 to 0.52; P = 0.002). By contrast, 3-year changes in TL were not associated with changes in cognitive function after 4 years. CONCLUSIONS: Longer baseline TL could protect from cognitive decline and be used as a useful biomarker of brain ageing function in an older Mediterranean population at risk of cardiovascular disease and cognitive impairment.

Exercise to combat cancer: focusing on the ends.

Cancer remains a leading cause of death worldwide and although prognosis and survivorship after therapy has improved significantly, current cancer treatments have long-term health consequences. For decades telomerase-mediated telomere maintenance has been an attractive anti-cancer therapeutic target due to its abundance and role in telomere maintenance, pathogenesis and growth in neoplasms. Telomere maintenance-specific cancer therapies, however, are marred by off target side-effects that must be addressed before they reach clinical practice. Regular exercise training is associated with telomerase-mediated telomere maintenance in healthy cells, which is associated with healthy ageing. A single bout of endurance exercise training dynamically, but temporarily, increases TERT mRNA and telomerase activity, as well as several molecules that control genomic stability and telomere length (i.e., shelterin and TERRA). Considering the epidemiological findings and accumulating research highlighting that exercise significantly reduces the risk of many types of cancers and the anti-carcinogenic effects of exercise on tumour growth in vitro, investigating the governing molecular mechanisms of telomerase control in context with exercise and cancer may provide important new insights to explain these findings. Specifically, the molecular mechanisms controlling telomerase in both healthy cells and tumours after exercise could reveal novel therapeutic targets for tumour-specific telomere maintenance and offer important evidence that could refine current physical activity and exercise guidelines for all stages of cancer care.

Effect of obesity and NAFLD on leukocyte telomere length and hTERT gene MNS16A VNTR variant.

It is known that telomere length (TL) (evaluated with T/S ratio) is shortened in the presence of obesity. In this study, we aimed to investigate how obesity in adolescents and non-alcoholic liver disease (NAFLD) within the obese group affect TL and the clinical significance of the human telomerase reverse transcriptase (hTERT) gene MNS16A VNTR variant in terms of NAFLD. Adolescents with exogenous obesity and healthy controls (aged 10-19 years) who applied to our adolescent outpatient clinic between May-October 2023 were included in this study. We performed upper abdominal ultrasonography to investigate the presence of NAFLD in adolescents with obesity and divided into two groups: those without hepatosteatosis (obese NAFLD (-)) and those with hepatosteatosis (obese NAFLD (+)). We recorded body weight, height, waist circumference, and blood pressure measurements and measured the T/S ratio (telomere sequence copy number/gene single copy number) by the Quantitative Polymerase Chain Reaction method. The groups were compared using frequentist and Bayesian methods. Eighty-three obese adolescents [63 NAFLD(+) 20 NAFLD(-)] and 69 lean controls were included in the study. Pairwise comparisons revealed that T/S ratio was significantly lower in the obese NAFLD (-) group than the obese NAFLD (+) and the control group (p = 0.025, p = 0.007, respectively). T/S ratio was lower in the LL allele group than in the other alleles (p = 0.022) and slightly higher in the obese group with metabolic syndrome compared to the obese group without metabolic syndrome (p = 0.072). hTERT-MNS16A-VNTR gene variant LL allele had a negative correlation with T/S ratio among the obese adolescent group. Patients with LL alleles had higher ALT, GGT, HOMA-IR, and ALT/AST. Diastolic blood pressure had a significant correlation with the T/S ratio. The T/S ratio was shorter in the obese adolescent group compared to healthy ones but was higher in the NAFLD (+) obese compared to the NAFLD (-) obese. ALT level and ALT/AST ratio were higher, T/S ratio was lower in the hTERT MNS16A VNTR variant LL allele group among obese adolescents. In addition, there was a significant correlation between the T/S ratio and diastolic blood pressure in obese adolescents.

Elevated 1-Hour Post Load Glucose as a Predictor for Telomere Attrition: a study based on a Chinese Community population.

CONTEXT: 1-hour post-load glucose (1h-PG) detects dysglycemia-related disorders more effectively than traditional glycemic parameters. Hyperglycemia accelerates aging, whether 1h-PG outperforms in predicting aging remains unclear. OBJECTIVE: To Compare the effectiveness of 1h-PG with other glycemic parameters in identifying and predicting telomere attrition. METHODS: We conducted a cross-sectional and longitudinal study based on a Chinese community cohort. Multivariate linear regression and logistic regression were used to analyze the associations between glycemic parameters and telomere length. The area under the receiver operating characteristic (AUROC) curve were used to compare the differentiating and predictive ability. Populations were regrouped by glucose tolerance status and 1h-PG to compare telomere length. Analyses were separately conducted in non-diabetic and diabetic populations. RESULTS: The cross-sectional study included 715 participants. Only 1h-PG was significantly negatively associated with RTL in both non-diabetic (ß = -0.106, 95%CI -0.068 to -0.007, P = 0.017) (odds ratio [OR] = 1.151, 95% CI 1.069 to 1.239, P = 0.005) and diabetic (ß = -0.222, 95%CI -0.032 to -0.007, P = 0.002) (OR = 1.144, 95% CI 1.041 to 1.258, P = 0.035) populations. The longitudinal study recruited 437 populations and 112 remained in 7-years follow-up. 1h-PG was associated with telomere shortening in the non-diabetic group (ß = -0.314, 95%CI -0.276 to -0.032, P = 0.016) (OR = 2.659, 95% CI 1.158 to 6.274, P = 0.021). AUROC analysis showed that 1h-PG outperformed other glycemic parameters in identifying and predicting telomere attrition. Reclassification revealed that normal glucose tolerance and prediabetic individuals with elevated 1h-PG had telomere lengths comparable to prediabetic and diabetic populations, respectively. CONCLUSIONS: 1h-PG outperforms other glycemic parameters in predicting telomere attrition and can be a valuable marker for early aging detection.

Hypertension Control Is Associated with Telomere Length in Older Adults.

Hypertension is the leading risk for cardiovascular disease and worldwide mortality. Uncontrolled blood pressure worsens with age and its control is part of public health strategies especially for older adults. Telomere length (TL) has been associated with hypertension, with age and sex as relevant confounding factors, but it is not clear whether hypertension control in older adults impacts on TL and if this relationship is consistently age and sex dependent. TL was assessed in leukocytes of 369 hypertensive patients. Individuals were >60 years male (169) and female (200) and have been diagnosed and treated for hypertension for at least four years. TL was measured by RT-PCR using a commercial probe. Regression models were developed considering systolic and diastolic blood pressure control as dependent variables and age, sex, glucose, and lipid levels as confounding factors. TL showed a mean of 7.5 ± 5.1 Kb, and no difference between males and females was observed. We identified a significant association between systolic blood pressure control and TL (p value = 0.039) and a trend for diastolic blood pressure (p value = 0.061). These observations confirm and expand previous reports showing that hypertension control can have an impact on TL and consequently on other factors of healthy aging.

A Natural Astragalus-Based Nutritional Supplement Lengthens Telomeres in a Middle-Aged Population: A Randomized, Double-Blind, Placebo-Controlled Study.

Telomeres are ribonucleoprotein structures that form a protective buffer at the ends of chromosomes, maintaining genomic integrity during the cell cycle. A decrease in average telomere length is associated with with age and with aging-related diseases such as cancer and cardiovascular disease. In this study, we conducted a randomized, double-blind, placebo-controlled trial over six months to compare the effects of the Astragalus-based supplement versus a placebo on telomere length (TL) in 40 healthy volunteers (mean age 56.1 ± 6.0 years). Twenty subjects received the supplement, and 20 received placebo capsules. All participants completed the study, and no adverse side effects were reported at six months. Subjects taking the Astragalus-based supplement exhibited significantly longer median TL (p = 0.01) and short TL (p = 0.004), along with a lower percentage of short telomeres, over the six-month period, while the placebo group showed no change in TL. This trial confirmed that the supplement significantly lengthens both median and short telomeres by increasing telomerase activity and reducing the percentage of short telomeres (<3 Kbp) in a statistically and possibly clinically significant manner. These results align with a previous open prospective trial, which found no toxicity associated with the supplement's intake. These findings suggest that this Astragalus-based supplement warrants further investigation for its potential benefits in promoting health, extending life expectancy, and supporting healthy aging.

Obesity-Senescence-Breast Cancer: Clinical Presentation of a Common Unfortunate Cycle.

There are few convincing studies establishing the relationship between endogenous factors that cause obesity, cellular aging, and telomere shortening. Without a functional telomerase, a cell undergoing cell division has progressive telomere shortening. While obesity influences health and longevity as well as telomere dynamics, cellular senescence is one of the major drivers of the aging process and of age-related disorders. Oxidative stress induces telomere shortening, while decreasing telomerase activity. When progressive shortening of telomere length reaches a critical point, it triggers cell cycle arrest leading to senescence or apoptotic cell death. Telomerase activity cannot be detected in normal breast tissue. By contrast, maintenance of telomere length as a function of human telomerase is crucial for the survival of breast cancer cells and invasion. Approximately three-quarters of breast cancers in the general population are hormone-dependent and overexpression of estrogen receptors is crucial for their continued growth. In obesity, increasing leptin levels enhance aromatase messenger ribonucleic acid (mRNA) expression, aromatase content, and its enzymatic activity on breast cancer cells, simultaneously activating telomerase in a dose-dependent manner. Meanwhile, applied anti-estrogen therapy increases serum leptin levels and thus enhances leptin resistance in obese postmenopausal breast cancer patients. Many studies revealed that shorter telomeres of postmenopausal breast cancer have higher local recurrence rates and higher tumor grade. In this review, interlinked molecular mechanisms are looked over between the telomere length, lipotoxicity/glycolipotoxicity, and cellular senescence in the context of estrogen receptor alpha-positive (ERα+) postmenopausal breast cancers in obese women. Furthermore, the effect of the potential drugs, which are used for direct inhibition of telomerase and the inhibition of human telomerase reverse transcriptase (hTERT) or human telomerase RNA promoters as well as approved adjuvant endocrine therapies, the selective estrogen receptor modulator and selective estrogen receptor down-regulators are discussed.