Telomere Length Research Articles

Immune response accelerated telomere shortening during early life stage of a passerine bird, the blue tit (Cyanistes caeruleus).

Dealing with infections is a daily challenge for wild animals. Empirical data show an increase in reactive oxygen species (ROS) production during immune response. This could have consequences on telomere length, the end parts of linear chromosomes, commonly used as proxy for good health and ageing. Telomere length dynamics may reflect the costs associated with physiological responses. In this study, immune system of blue tit (Cyanistes caeruleus) nestlings was experimentally challenged through a polyinosinic:polycytidylic acid (poly I:C) injection, a synthetic double-stranded RNA that mimics a virus, activating the pathway of immune response triggered via the toll-like receptors 3. This path is known to form ROS downstream. Immune response was quantified by white cell counts in blood, while brain lipoperoxidation has been evaluated as an indicator of oxidative damage. Finally, individuals' telomere length shortening between days 8 and 15 after hatching was measured in erythrocytes. Challenged nestlings showed increased leukocyte number when compared with control (treated with a saline solution), lower brain lipid peroxidation (likely as a result of a compensatory mechanism after oxidative stress burst) and accelerated telomere shortening. These findings support the 'ageing cost of infections pathway' hypothesis, which supposes a role for infections in quick biological ageing.

Association of polycystic ovary syndrome with endothelial health, cardiovascular risk, and cellular aging.

To study measures of endothelial health, cardiovascular risk, and cellular aging between patients with polycystic ovary syndrome (PCOS) and a reproductive age normative cohort. Cross-sectional study. Community-based patients with PCOS and a normative ovarian aging cohort as controls, aged ≤45 years at the time of evaluation. Noninvasive measure of endothelial health measured by the EndoPAT reactive hyperemia index. Reactive hyperemia index as measure of endothelial health. The secondary outcomes included Framingham score, telomere length, and mitochondrial deoxyribonucleic acid copy number from leukocyte cells. Our cohort included 63 participants with PCOS and 130 non-PCOS participants. The mean age was significantly lower in the PCOS cohort (33.1; standard deviation, 4.7 years) than in the non-PCOS cohort (40.8; standard deviation, 2.9 years). In multivariable-adjusted models, we found that PCOS was significantly associated with endothelial dysfunction as both categorical (odds ratio for PCOS, 0.31; 95% confidence interval [CI], 0.10-0.97) and continuous (PCOS coefficient, -0.37; 95% CI, -0.69 to -0.05) outcomes. For secondary outcomes, PCOS status was not significantly associated with mitochondrial deoxyribonucleic acid (PCOS coefficient, -48.1; 95% CI, -175.0 to 78.9), telomere length (PCOS coefficient, 0.05; 95% CI, -0.05 to 0.15), Framingham score (PCOS coefficient, 0.002; 95% CI, -0.01 to 0.02), or metabolic syndrome (odds ratio for PCOS, 1.29; 95% CI, 0.31-5.44). Our findings suggest that patients with PCOS have impaired endothelial function compared with non-PCOS patients, although measures of cellular aging and cardiovascular risk as measured by the Framingham score did not differ between the cohorts.

Yoga Practice as a Potential Sarcopenia Prevention Strategy in Indonesian Older Adults: A Cross-Sectional Study.

Sarcopenia is characterized by the progressive loss of skeletal muscle mass and poses a significant health challenge for older adults by increasing the risk of disability and decreasing quality of life. Yoga considers as a low-risk and beneficial exercise for older adults. This research aims to evaluate the potential of yoga practice as a preventive strategy against sarcopenia in Indonesian older adults. An observational cross-sectional research was conducted including 41 older adults aged 60-87 years. The research focused on key biomarkers and functional assessments, including serum insulin-like growth factor 1 (IGF-1) levels, telomere length, gait speed, hand grip strength, and SARC-F questionnaire scores. The results showed that participants aged 71-80 years who practiced yoga for more than a year had significantly higher IGF-1 levels (p=0.04). While improvements in gait speed, hand grip strength, and SARC-F scores were observed, these changes were not statistically significant, and no significant differences were found in telomere length. Yoga in older adults was associated with higher IGF-1 levels and potential improvements in upper and lower extremity strength, though these findings were not statistically significant and did not influence telomere length. Yoga practice shows potential as an emerging adjuvant option but can not be applied as a single strategy for sarcopenia prevention in older adults.

The RNA-binding protein CMSS1 promotes the progression of non-small cell lung cancer by regulating the telomerase protein subunit hTERT.

High telomerase activity has been detected in over 85 % of tumors, with the activation of hTERT being the most crucial mechanism for re-establishing telomerase activity. Activation of hTERT maintains telomere length in cells, enabling cancer cells to proliferate indefinitely. Nevertheless, the specific mechanism of telomerase activation in non-small cell lung cancer (NSCLC) remains unclear, and post-transcriptional regulation of hTERT could be a potential activation mechanism. We explored the regulatory impact of CMSS1 on hTERT expression in NSCLC cells using several methods: Yeast three-hybrid system, Reporter gene assay, Western blot, RNA decay assay, and Telomere length measurement. Our analysis revealed significant overexpression of CMSS1 in NSCLC, which correlated with poor prognosis, as determined by bioinformatics and tissue microarray techniques. RNA sequencing analysis showed that CMSS1 knockdown influenced the adhesion capabilities of NSCLC cells. Additionally, potential interacting proteins with CMSS1 were identified through mass spectrometry and co-immunoprecipitation experiments. We discovered that CMSS1 regulates hTERT expression in NSCLC cells by binding to the 5' UTR of hTERT mRNA, impacting its mRNA stability and thereby influencing NSCLC progression. RNA-Seq results and adhesion experiments indicated that CMSS1 knockdown disrupts cell adhesion. hTERT also affects cell adhesion in NSCLC, underscoring CMSS1's role as an upstream regulator of hTERT. Mass spectrometry and Co-IP studies suggest potential interactions between CMSS1, RBM34, and DDX5 that further modulate hTERT expression. These findings indicate that CMSS1 plays a crucial role in NSCLC progression through its interaction with hTERT, making it a promising therapeutic target.

Association of urban green and blue space with accelerated ageing: A cohort Study in the UK Biobank.

We investigated the associations between urban green and blue spaces and the incidence of accelerated ageing, which have rarely been studied. Analyzed UK Biobank data (2006-2010) on 440,785 participants, focusing on urban green and blue space (UGBS). General linear models and logistics models assessed links between UGBS and accelerated ageing (Klemera-Doubal method, telomere length and frailty). Mediation analysis examined the role of pollution and other factors. After controlling for random effects and various types of covariates, we found that 1) populations with higher levels of UGBS exposure are associated with accelerated ageing and slowing down; 2) UGBS has the greatest impact on accelerated ageing within a 1000-m street network buffer distance; 3) Participants living in heavily polluted areas should pay more attention to UGBS; 4) Intermediary analysis found that UGBS mainly accelerates aging by reducing harm, rather than affecting the population's ability to recover and build. UGBS with a composite weighted score showed a better correlation with accelerated ageing than green spaces. Other factors such as gender, race and lifestyle also influence the impact of the environment on accelerated ageing.

The Role of Optimism, Connectedness, and Neighborhood Collective Efficacy as Moderators of Harsh Parenting on Telomere Length

The Role of Optimism, Connectedness, and Neighborhood Collective Efficacy as Moderators of Harsh Parenting on Telomere Length

Clinical impact of donor telomere length after umbilical cord blood transplantation

Clinical impact of donor telomere length after umbilical cord blood transplantation

Great Tit (Parus major) Nestlings Have Longer Telomeres in Old-Growth Forests Than in Young Forests.

Modification and deterioration of old-growth forests by industrial forestry have seriously threatened species diversity worldwide. The loss of natural habitats increases the concentration of circulating glucocorticoids and incurs chronic stress in animals, influencing the immune system, growth, survival, and lifespan of animals inhabiting such areas. In this study, we tested whether great tit (Parus major) nestlings grown in old-growth unmanaged coniferous forests have longer telomeres than great tit nestlings developing in young managed coniferous forests. This study showed that the patches of young managed coniferous forests had lower larval biomass than old-growth forests. Since insect larvae are the preferred food for great tit nestlings, the shortage of food may divert energy resources away from growth, which can show up as physiological stress, often raising the heterophil/lymphocyte (H/L) ratio. The H/L ratio revealed a significant difference in stress levels, being the highest in great tit nestlings developing in young-managed pine forests. We also found that the development of great tit nestlings in young managed forests had significantly shorter telomeres than in old-growth forests. Although nestling survival did not differ between the habitats, nestlings growing up in old-growth forests had greater telomere lengths, which can positively affect their lifespan. Our results suggest that the forest habitats affected by industrial forestry may represent ecological traps, as the development of young birds in deteriorated environments can affect the age structure of populations.

Biomolecular Condensates in Telomere Maintenance of ALT Cancer Cells.

Alternative Lengthening of Telomeres (ALT) pathway is a telomerase-independent mechanism that utilizes homology-directed repair (HDR) to sustain telomere length in specific cancers. Biomolecular condensates, such as ALT-associated promyelocytic leukemia nuclear bodies (APBs), have emerged as critical players in the ALT pathway, supporting telomere maintenance in ALT-positive cells. These condensates bring together DNA repair proteins, telomeric repeats, and other regulatory elements. By regulating replication stress and promoting DNA synthesis, ALT condensates create an environment conducive to HDR-based telomere extension. This review explores recent advancements in ALT, focusing on understanding the role of biomolecular condensates in ALT and how they impact telomere dynamics and stability.

Drivers of sperm telomere length variability in a wild bird

Drivers of sperm telomere length variability in a wild bird

Deciphering the bidirectional impact of leukocyte telomere length on multiple sclerosis progression: A Mendelian randomization study.

Observational studies have suggested a link between leukocyte telomere length (LTL) and multiple sclerosis (MS) progression, but the causal relationship remains uncertain. This study investigates the causal association between LTL and MS progression using a bidirectional two-sample Mendelian randomization (MR) approach. We analyzed genome-wide association summary statistics data from 472,174 individuals for LTL and 12,584 MS patients for disease progression. The primary method was the inverse variance weighted (IVW) approach, supported by sensitivity analyses to ensure robustness. The forward analysis revealed a significant positive causal relationship between LTL and MS progression (β = 0.107, 95 % CI = 0.006 to 0.209, P = 0.037). Conversely, the reverse analysis indicated a negative causal relationship (β = -0.010, 95 % CI = -0.020 to -0.001, P = 0.037). No heterogeneity or horizontal pleiotropy was found, and the sensitivity analyses confirmed consistent results. These findings suggest that telomere dynamics play a complex role in MS progression and highlight their potential as therapeutic targets. Further research is essential to uncover the biological mechanisms underlying the influence of telomeres on MS progression.

Oral intake of degalactosylated whey protein increases peripheral blood telomere length in young and aged mice

In order to elucidate novel actions of degalactosylated whey protein (D-WP) in comparison with intact whey protein (WP), the effects of oral intake of D-WP on peripheral blood telomere length and telomerase were examined in young and aged mice. In young mice, peripheral blood telomere length was significantly elongated following oral intake of D-WP for 4 weeks. mRNA expression of both telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) was significantly increased in the peripheral blood following oral intake of D-WP for 4 weeks. In aged mice, peripheral blood telomere length was significantly decreased as compared with that of young mice, and significantly restored to the level of young mice drinking water by the oral intake of D-WP for 4 weeks. The mRNA expression of peripheral blood TERT and TERC mRNA in aged mice significantly decreased as compared with the level in young mice drinking water, and was significantly restored to the level of expression of young mice drinking water by oral intake of D-WP for 4 weeks. These results suggest that D-WP, but not WP, potently increases peripheral blood telomere length accompanied by increased mRNA expression of TERT and TERC in both young and aged mice.

Telomere length and telomerase activity in men and non-pregnant women with and without metabolic syndrome: a systematic review and bootstrapped meta-analysis.

We performed a systematic review and meta-analysisto examine the associations between telomere length and telomerase activity in subjects with and without metabolic syndrome (MetS). The meta-analysis protocol was registered in the PROSPERO database. The PubMed, Embase, Cochrane Library, and LILACS databases were searched for studies reporting telomere length or telomerase activity in adult men and non-pregnant women with and without MetS. The risk of bias was assessed with the Newcastle-Ottawa Scale. Random effects and inverse variance methods were used to meta-analyze associations. We conducted a bootstrapped analysis to test the accuracy of clinical results. Five studies reported telomere length and two studies telomerase activity. There was no significant difference in telomere length (standardized mean difference [SMD]: 0.10, 95% confidence interval [CI]: -0.07, 0.28, I 2: 54%), between subjects of similar age (mean difference: 2.68, 95%CI: -0.04, 5.40 years) with and without the MetS. Subjects with MetS displayed significantly higher body mass index, triglycerides, and blood pressure, and lower HDL-cholesterol values than subjects without the syndrome. A bootstrapping mediation analysis of telomere length confirmed the clinical results. There was no significant difference in telomerase activity (SMD: 1.19, 95% CI -0.17, 2.55, I 2: 93%) between subjects with and without the MetS. There were no significant differences of telomere length and telomerase activity in patients with MetS and subjects of similar age without the syndrome. The online version contains supplementary material available at 10.1007/s40200-024-01513-4.

Telomere length sensitive regulation of interleukin receptor 1 type 1 (IL1R1) by the shelterin protein TRF2 modulates immune signalling in the tumour microenvironment

Telomeres are crucial for cancer progression. Immune signalling in the tumour microenvironment has been shown to be very important in cancer prognosis. However, the mechanisms by which telomeres might affect tumour immune response remain poorly understood. Here, we observed that interleukin-1 signalling is telomere-length dependent in cancer cells. Mechanistically, non-telomeric TRF2 (telomeric repeat binding factor 2) binding at the IL-1-receptor type-1 (IL1R1) promoter was found to be affected by telomere length. Enhanced TRF2 binding at the IL1R1 promoter in cells with short telomeres directly recruited the histone-acetyl-transferase (HAT) p300, and consequent H3K27 acetylation activated IL1R1. This altered NF-kappa B signalling and affected downstream cytokines like IL6, IL8, and TNF. Further, IL1R1 expression was telomere-sensitive in triple-negative breast cancer (TNBC) clinical samples. Infiltration of tumour-associated macrophages (TAM) was also sensitive to the length of tumour cell telomeres and highly correlated with IL1R1 expression. The use of both IL1 Receptor antagonist (IL1RA) and IL1R1 targeting ligands could abrogate M2 macrophage infiltration in TNBC tumour organoids. In summary, using TNBC cancer tissue (>90 patients), tumour-derived organoids, cancer cells, and xenograft tumours with either long or short telomeres, we uncovered a heretofore undeciphered function of telomeres in modulating IL1 signalling and tumour immunity.

From cells to recapture rates: responses and recovery of a wild fish after an experimental exposure to a widely used herbicide.

Freshwater environments are biodiversity hotspots under multiple pressures, including pesticide exposure. S-metolachlor, a widely used herbicide, can induce genotoxic, cytotoxic and physiological effects in captive fish, but we have a limited understanding of the effects of exposure to S-metolachlor in free-living vertebrates. We carried out an original field experiment using integrative approaches across biological levels and temporal scales. The implantation of slow-release implants, an approach to mimic increasing exposure to S-metolachlor of wildlife in realistic multistress conditions, was coupled to a capture-mark-recapture monitoring of bullheads (Cottus perifretum) living in an agriculturally impacted stream. Thanks to our long-term monitoring programme, we evidenced high levels of metolachlor and its metabolites (metolachlor ESA and metolachlor OXA) in water bodies with strong monthly variations. S-metolachlor levels did not differ between treated and control fish and were moderate in bullhead tissues, likely because of xenobiotic metabolism and excretion. S-metolachlor exposure increased erythrocyte abnormalities and the neutrophil/lymphocyte (N/L) ratios. These cellular and physiological damages were observed at 2weeks, but not at 3months after the manipulation. This suggests a recovery, likely owing to cell turnover. We also found an increase of body mass of treated fish compared to control fish, and this mass gain persisted at 3months, suggesting obesogenic effects of S-metolachlor. Antioxidant levels, telomere length and recapture rate were not affected by the experimental treatment. In conclusion, we provide evidence for transient and specific cellular alterations induced by low concentrations of S-metolachlor and long-term mass gain in a wild vertebrate. This study paves the way for integrative field experiments to better understand the impacts of pollutants on fish populations.

Telomere length sensitive regulation of interleukin receptor 1 type 1 (IL1R1) by the shelterin protein TRF2 modulates immune signalling in the tumour microenvironment.

Telomeres are crucial for cancer progression. Immune signalling in the tumour microenvironment has been shown to be very important in cancer prognosis. However, the mechanisms by which telomeres might affect tumour immune response remain poorly understood. Here, we observed that interleukin-1 signalling is telomere-length dependent in cancer cells. Mechanistically, non-telomeric TRF2 (telomeric repeat binding factor 2) binding at the IL-1-receptor type-1 (IL1R1) promoter was found to be affected by telomere length. Enhanced TRF2 binding at the IL1R1 promoter in cells with short telomeres directly recruited the histone-acetyl-transferase (HAT) p300, and consequent H3K27 acetylation activated IL1R1. This altered NF-kappa B signalling and affected downstream cytokines like IL6, IL8, and TNF. Further, IL1R1 expression was telomere-sensitive in triple-negative breast cancer (TNBC) clinical samples. Infiltration of tumour-associated macrophages (TAM) was also sensitive to the length of tumour cell telomeres and highly correlated with IL1R1 expression. The use of both IL1 Receptor antagonist (IL1RA) and IL1R1 targeting ligands could abrogate M2 macrophage infiltration in TNBC tumour organoids. In summary, using TNBC cancer tissue (>90 patients), tumour-derived organoids, cancer cells, and xenograft tumours with either long or short telomeres, we uncovered a heretofore undeciphered function of telomeres in modulating IL1 signalling and tumour immunity.

The Role of Leukocyte Telomere Length in Cognitive Function, Symptom Severity, and Sdg-Related Health Goals Among Batak Schizophrenia Patients

Objective: To assess the relationship between leukocyte telomere length, cognitive function, and symptom severity in Batak tribe schizophrenia patients, with a focus on telomere length as a potential biomarker for disease progression and its relevance to Sustainable Development Goal (SDG) 3: Good Health and Well-being. Theoretical Framework: This study builds on findings linking leukocyte telomere shortening to accelerated aging, cognitive decline, and increased risks of neurodegenerative diseases and cancer. These connections underscore the importance of telomere length as a marker of symptom severity in schizophrenia and its alignment with global health objectives under the SDGs. Method: A 6-month cross-sectional study design with numerical correlation tests was used from January to June 2023. Eighty-five patients from the Batak tribe diagnosed with schizophrenia were recruited from Regional Mental Hospital Prof. Dr. M. Ildrem Medan, and telomere length analysis was conducted at Prodia Private Clinical Laboratory in Medan. Results and Discussion: The sample included 85 patients, mostly male (80%) with a mean age of 30.38 years (SD: 3.2). Cognitive function showed a mean MoCA-Ina score of 17.33 (SD: 5.4), and symptom severity showed a mean PANSS score of 48.87 (SD: 9.73). Leukocyte telomere length ratios were 0.92 (SD: 0.04) for β-globin T/S and 0.99 (SD: 0.05) for B4AU T/S. No significant link was found between telomere length and cognitive function (p>0.05), but shorter telomeres correlated with more severe symptoms (β-globin T/S: p=0.034, r=-0.23; B4AU T/S: p=0.037, r=-0.227). Research Implications: Findings indicate that leukocyte telomere length could serve as a biomarker for schizophrenia symptom severity, offering valuable insights for disease progression and contributing to health monitoring strategies aligned with SDG 3. Originality/Value: By focusing on the Batak tribe, this study highlights telomere length as a biomarker for prognosis and underscores the importance of diverse population studies to achieve SDG-related health outcomes.

Lipid Profiles, Telomere Length, and the Risk of Malignant Tumors: A Mendelian Randomization and Mediation Analysis.

Background/Objectives: The relationship between lipid profiles, telomere length (TL), and cancer risk remains unclear. Methods: This study employed two-sample Mendelian randomization (MR) with mediation analysis to investigate their causal relationships, examining lipid profiles as exposure, TL as mediator, and nine cancer types as outcomes. We conducted our analysis using two-stage least squares (2SLS) regression integrated with inverse variance weighted (IVW) methods to address potential endogeneity and strengthen our causal inference. Results: we found that unfavorable lipid profiles were causally linked to increased TL (p < 0.05). TL showed positive causal associations with lung and hematologic cancers (OR > 1, p < 0.05). Direct associations were observed between total and low-density lipoprotein (LDL) cholesterol and gastric cancer (OR < 1, p < 0.05), and between remnant cholesterol and colorectal cancer (OR > 1, p < 0.05). Mediation analysis revealed TL as a significant mediator in the pathway from lipid profiles to cancer development (p < 0.05). No horizontal pleiotropy was detected. Conclusions: Our findings suggest that lipid metabolism disorders may influence cancer development through telomere regulation, particularly in lung and hematologic cancers. This emphasizes the importance of lipid management in cancer prevention and treatment, especially for these cancer types.

Biological Aging and Venous Thromboembolism: A Review of Telomeres and Beyond.

Although venous thromboembolism (VTE) is the third most common cardiovascular disease, and the risk of VTE increases sharply with advancing age, approximately 40% of VTE cases are currently classified as unprovoked, highlighting the importance of risk factor research. While chronological aging is associated with the risk of VTE, the association with biological aging remains unclear. Biological aging is highly complex, influenced by several dysregulated cellular and biochemical mechanisms. In the last decade, advancements in omics methodologies provided insights into the molecular complexity of biological aging. Techniques such as high-throughput genomics, epigenomics, transcriptomics, proteomics, and metabolomics analyses identified and quantified numerous epigenetic markers, transcripts, proteins, and metabolites. These methods have also revealed the molecular alterations organisms undergo as they age. Despite the progress, there is still a lack of consensus regarding the methods for assessing and validating these biomarkers, and their application lacks standardization. This review gives an overview of biomarkers of biological aging, including telomere length, and their potential role for VTE. Furthermore, we critically examine the advantages and disadvantages of the proposed methods and discuss possible future directions for investigating biological aging in VTE.

A novel method for telomere length detection in fission yeast.

Fission yeast is the ideal model organism for studying telomere maintenance in higher eukaryotes. Telomere length has been directly correlated with life expectancy and the onset of aging-related diseases in mammals. In this study, we developed a novel simple, and reproducible method to measure the telomere length, by investigating the effect of caffeine and cisplatin on the telomere length in fission yeast. Hydroxyurea-synchronized fission yeast cells were exposed to 62 µM cisplatin and 8.67mM caffeine treatments for 2 h, then their telomere lengths were evaluated with two different methods. First, the quantitative polymerase chain reaction (qPCR) assay was used as a confirmative method, where telomere length was determined relative to a single-copy gene in the genome. Second, the newly developed method standard polymerase chain reaction (PCR)/ImageJ assay assessed the telomere length based on the amplified PCR band intensity using a set of telomere primers, reflecting telomeric sequence availability in the genome. Both methods show a significant decrease and a notable telomere lengthening in response to cisplatin and caffeine treatments, respectively. The finding supports the accuracy and productivity of the standard PCR/ImageJ assay as it can serve as a quick screening tool to study the effect of suspected chemotherapeutic and antiaging drugs on telomere length in fission yeast.