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Telomeres are pivotal determinants of cell stemness, organismal aging, and lifespan. Herein, we examined similarities in telomeres of Arabidopsis thaliana, mice, and humans. We report the common traits, which include their composition in multimers of TTAGGG sequences and their protection by specialized proteins. Moreover, given the link between telomeres, on the one hand, and cell proliferation and stemness on the other, we discuss the counterintuitive convergence between plants and mammals in this regard, focusing on the impact of niches on cell stemness. Finally, we suggest that tackling the study of telomere function and cell stemness by taking into consideration both plants and mammals can aid in the understanding of interconnections and contribute to research focusing on aging and organismal lifespan determinants. [ABSTRACT FROM AUTHOR]

Background & aims: Sarcopenia is common in patients with liver disease and both sarcopenia and short telomeres are associated with mortality, however their relationship in patients with liver disease remains unknown. Methods: A cohort of 16,072 adults from the National Health and Nutrition Examination Survey from 1999 to 2006 was analyzed. Liver disease was defined by aminotransferases and classified into etiology-based categories. Sarcopenia was defined by dual-energy x-ray absorptiometry. All analyses were conducted separately on each multiple imputation data set and combined via Rubin's rules. P-values for group comparisons were calculated by testing logistic regression parameter estimates. Cox proportional hazards regression was used for mortality analysis with mortality data available until 2015. Results: Sarcopenia was present in 9.5% of patients with liver disease. Age, race, income, education, physical inactivity, and certain medical comorbidities were associated with sarcopenia. Patients with liver disease and sarcopenia had significantly shorter telomeres than patients with liver disease without sarcopenia when unadjusted for age. The interaction between telomere length and sarcopenia was significantly associated with all-cause mortality. Conclusions: The implications of telomere length on all-cause mortality in patients with liver disease varied by age and sarcopenia status. Shorter telomeres appear to be more highly associated with increased mortality in older patients without sarcopenia. [ABSTRACT FROM AUTHOR]

Background: 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. Goals: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Telomere 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. Methods: Using 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. Results: The 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 (훽 = -0.024; 95%CI: -0.050 to 0.001; P = 0.058), the Non-Hispanic White (훽 = -0.022; 95%CI: -0.045 to 0.002; P = 0.066), and other race (훽 = -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). Conclusions: This 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The bi- or multinucleated Reed–Sternberg cell (RS) is the diagnostic cornerstone of Epstein–Barr Virus (EBV)-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL is a germinal center (GC)-derived B-cell disease. Hodgkin cells (H) are the mononuclear precursors of RS. An experimental model has to fulfill three conditions to qualify as common pathogenic denominator: (i) to be of GC-derived B-cell origin, (ii) to be EBV-negative to avoid EBV latency III expression and (iii) to support permanent EBV-encoded oncogenic latent membrane protein (LMP1) expression upon induction. These conditions are unified in the EBV-, diffuse large B-Cell lymphoma (DLBCL) cell line BJAB-tTA-LMP1. 3D reconstructive nanotechnology revealed spatial, quantitative and qualitative disturbance of telomere/shelterin interactions in mononuclear H-like cells, with further progression during transition to RS-like cells, including progressive complexity of the karyotype with every mitotic cycle, due to BBF (breakage/bridge/fusion) events. The findings of this model were confirmed in diagnostic patient samples and correlate with clinical outcomes. Moreover, in vitro, significant disturbance of the lamin AC/telomere interaction progressively occurred. In summary, our research over the past three decades identified cHL as the first lymphoid malignancy driven by a disturbed telomere/shelterin/lamin AC interaction, generating the diagnostic RS. Our findings may act as trailblazer for tailored therapies in refractory cHL. [ABSTRACT FROM AUTHOR]

SUMMARY: Genome stability is significantly influenced by the precise coordination of chromatin complexes that facilitate the loading and eviction of histones from chromatin during replication, transcription, and DNA repair processes. In this study, we investigate the role of the Arabidopsis H3 histone chaperones ANTI‐SILENCING FUNCTION 1 (ASF1) and HISTONE REGULATOR A (HIRA) in the maintenance of telomeres and 45S rDNA loci, genomic sites that are particularly susceptible to changes in the chromatin structure. We find that both ASF1 and HIRA are essential for telomere length regulation, as telomeres are significantly shorter in asf1a1b and hira mutants. However, these shorter telomeres remain localized around the nucleolus and exhibit a comparable relative H3 occupancy to the wild type. In addition to regulating telomere length, ASF1 and HIRA contribute to silencing 45S rRNA genes and affect their copy number. Besides, ASF1 supports global heterochromatin maintenance. Our findings also indicate that ASF1 transiently binds to the TELOMERE REPEAT BINDING 1 protein and the N terminus of telomerase in vivo, suggesting a physical link between the ASF1 histone chaperone and the telomere maintenance machinery. [ABSTRACT FROM AUTHOR]

Characterization of long non-coding telomeric repeat-containing RNAs in sperm of normozoospermic and oligoasthenozoospermic men as new biomarker of idiopathic male infertility. We conducted an observational prospective study with two groups of men with normal or orligoasthenozoospermic spermiogram, aged 40 and above. Fertility parameters were analyzed in men undergoing intracytoplasmic sperm injection with donor oocytes, to avoid the female factor. Telomeric RNAs and telomere length were measured by quantitative fluorescent in situ hybridization. Data from seminal parameters and in-vitro fertilization were assessed according to IVIRMA protocols. Patients with oligoasthenozoospermia, who had worse seminal parameters, also obtained embryos with lower inner-cell-mass quality (p = 0.04), despite using donor oocytes. While mean levels of telomeric RNAs were similar for both groups, the percentage of spermatozoa with more than 3 foci was higher in oligoasthenozoospermic men (p = 0.02). Regarding telomere length, oligoasthenozoospermic men had shorter mean, a higher accumulation of short telomeres (15th percentile; p = 0.03) and a lower percentage of very-long telomeres (85th percentile; p = 0.01). Finally, a positive correlation was found between telomeric-RNAs intensity and total progressive motility in the spermatozoa of normozoospermic patients (r = 0.5; p = 0.03). Telomeric parameters were altered in the spermatozoa of the oligoasthenozoospermic group, which also showed lower quality embryos. Interestingly, in the normozoospermic group, a correlation was found between progressive motility and telomeric RNA levels, suggesting that they could be a good biomarker of sperm quality. Further studies are required to confirm these results and translate them into the clinical practice. Trial registration number: 1711-MAD-109-CB, 07/07/2021. [ABSTRACT FROM AUTHOR]

Telomeres undergo a progressive shortening process as individuals age, and it has been proposed that severely shortened and dysfunctional telomeres play a role in the aging process and the onset of age-related diseases in human beings. An emerging body of evidence indicates that the shortening of telomeres in cultured human cells is also influenced by other replication defects occurring within telomeric repeats. These abnormalities can be detected on metaphase chromosomes. Recent studies have also identified a set of serological markers for telomere dysfunction and DNA damage (elongation factor 1α [EF-1α], stathmin, and N-acetyl-glucosaminidase). With this study, the correlation between telomere abnormalities (by FISH) and these biomarkers as measured in blood serum (by ELISA) from a cohort of 22 healthy subjects at different ages (range 26–101 years) was analyzed. A strong positive correlation between aging and the presence of aberrant telomere structures, sister telomere loss (STL), and sister telomere chromatid fusions (STCF) was detected. When serum markers of telomere dysfunction were correlated with telomere abnormalities, we found that stathmin correlated with total aberrant telomeres structures (r = 0.431, p = 0.0453) and STCF (r = 0.533, p = 0.0107). These findings suggest that serum stathmin can be considered an easy-to-get marker of telomere dysfunction and may serve as valuable indicators of aging. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Telomeres are the protective caps at the ends of linear chromosomes of eukaryotic organisms. Telomere binding proteins, including the six components of the complex known as shelterin, mediate the protective function of telomeres. They do this by suppressing many arms of the canonical DNA damage response, thereby preventing inappropriate fusion, resection and recombination of telomeres. One way this is achieved is by facilitation of DNA replication through telomeres, thus protecting against a "replication stress" response and activation of the master kinase ATR. On the other hand, DNA damage responses, including replication stress and ATR, serve a positive role at telomeres, acting as a trigger for recruitment of the telomere-elongating enzyme telomerase to counteract telomere loss. We postulate that repression of telomeric replication stress is a shared mechanism of control of telomerase recruitment and telomere length, common to several core telomere binding proteins including TRF1, POT1 and CTC1. The mechanisms by which replication stress and ATR cause recruitment of telomerase are not fully elucidated, but involve formation of nuclear actin filaments that serve as anchors for stressed telomeres. Perturbed control of telomeric replication stress by mutations in core telomere binding proteins can therefore cause the deregulation of telomere length control characteristic of diseases such as cancer and telomere biology disorders. [ABSTRACT FROM AUTHOR]

G-quadruplexes refer to a large group of nucleic acid–based structures. In recent years, they have been attracting attention due to their biological roles in the telomeres and promoter regions. These structures show wide diversity in topology, however, development of methods for structural classification of G-quadruplexes has been evaded for a long time. There has been a limited number of studies aiming to bring forth a secondary structure classification method. The situation was even more complex than imagined, since the discovery of bulged and mismatched G-quadruplexes while most of the available tools fail to distinguish these non-canonical G-quadruplex motifs. Moreover, the interpretation of their analysis output still requires expert knowledge. In this study, we propose a new method for identification of unimolecular G-Quadruplexes and classification by secondary structures based on three-dimensional structural data. Briefly, coordinates of guanines are processed to identify tetrads, loops and bulges. Then, we present the secondary structure in the form of a depiction which shows the loop types, bulges, and guanines that participate in each tetrad. Moreover, CIIS-GQ identifies non-guanine nucleotides that joins the G-tetrads and forms multiplets. Finally, the results of our study are compared with DSSR and ElTetrado classification methods, and the advantages of the proposed depiction method for representing secondary structures were discussed. The source code of the method can be accessed via https://github.com/TugayDirek/CIIS-GQ. [ABSTRACT FROM AUTHOR]

Background: Biological aging is a complex process influenced by various factors, including reproductive status and castration. This study aimed to evaluate the impact of castration on biological aging in dogs. Method: Fifteen male crossbred dogs were randomly divided into a sham-operation control group (n = 5) and a castrated group (n = 10). Blood samples were collected at weeks 0, 4, 8, 12, 16, and 18 post-surgery. Malondialdehyde (MDA as indicator of Lipid peroxidation), C-reactive protein (as an indicator of inflammation), telomere length, mitochondrial DNA (mtDNA) copy number, and the expression of age-related (P16, P21, TBX2) and telomerase-related (TERT) genes were assessed in blood samples. Results: Plasma MDA levels were higher in the control group at weeks 16 and 18, while CRP levels were higher only at week 18. Telomere length and mtDNA copy number were lower in the control group at week 18. Gene expression analysis showed that P16 was lower in the control group at weeks 8 and 12, P21 and TERT were lower at weeks 16 and 18, and TBX2 was lower at weeks 16 and 18. The TBX2/P16 ratio was lower in the control group at weeks 16 and 18 but higher at week 12, while the TBX2/P21 ratio did not differ between groups. Conclusion: Castration appears to have a protective effect against biological aging in dogs, as evidenced by lower lipid peroxidation, inflammation, and age-related changes in telomere length, mtDNA copy number, and gene expression. [ABSTRACT FROM AUTHOR]

Telomeres are protective structures at the end of eukaryotic chromosomes that are strongly implicated in ageing and ill health. They attrition upon every cellular reproductive cycle. Evidence suggests that short telomeres trigger DNA damage responses that lead to cellular senescence. Accurate methods for measuring telomeres are required to fully investigate the roles that shortening telomeres play in the biology of disease and human ageing. The last two decades have brought forth several techniques that are used for measuring telomeres. This editorial highlights strengths and limitations of traditional and emerging techniques, guiding researchers to choose the most appropriate methodology for their research needs. These methods include Quantitative Polymerase Chain Reaction (qPCR), Omega qPCR (Ω-qPCR), Terminal Restriction Fragment analysis (TRF), Single Telomere Absolute-length Rapid (STAR) assays, Single TElomere Length Analysis (STELA), TElomere Shortest Length Assays (TESLA), Telomere Combing Assays (TCA), and Long-Read Telomere Sequencing. Challenges include replicating telomere measurement within and across cohorts, measuring the length of telomeres on individual chromosomes, and standardised reporting for publications. Areas of current and future focus have been highlighted, with recent methodical advancements, such as long-read sequencing, providing significant scope to study telomeres at an individual chromosome level. [ABSTRACT FROM AUTHOR]

Appropriate repair of damaged DNA and the suppression of DNA damage responses at telomeres are essential to preserve genome stability. DNA damage response (DDR) signaling consists of cascades of kinase-driven phosphorylation events, fine-tuned by proteolytic and regulatory ubiquitination. It is not fully understood how crosstalk between these two major classes of post-translational modifications impact DNA repair at deprotected telomeres. Hence, we performed a functional genetic screen to search for ubiquitin system factors that promote KAP1S824 phosphorylation, a robust DDR marker at deprotected telomeres. We identified that the OTU family deubiquitinase (DUB) OTUD5 promotes KAP1S824 phosphorylation by facilitating ATM activation, through stabilization of the ubiquitin ligase UBR5 that is required for DNA damage-induced ATM activity. Loss of OTUD5 impairs KAP1S824 phosphorylation, which suppresses end-joining mediated DNA repair at deprotected telomeres and at DNA breaks in heterochromatin. Moreover, we identified an unexpected role for the heterochromatin factor KAP1 in suppressing DNA repair at telomeres. Altogether our work reveals an important role for OTUD5 and KAP1 in relaying DDR-dependent kinase signaling to the control of DNA repair at telomeres and heterochromatin. Ubiquitination factors play crucial roles in DNA repair. The authors show that deubiquitinase OTUD5 facilitates ATM-dependent DNA damage signalling via the UBR5-ATMIN axis. OTUD5 loss results in DNA repair defects at heterochromatin and deprotected telomeres due to insufficient KAP1S824 phosphorylation. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory bowel disease (IBD) remains a major public health challenge worldwide. In recent years, it has been discovered that a link between telomere shortening and disease progression in IBD patients has been present. However, there is controversy as to whether telomere shortening precipitates disease progression or disease progression causes telomere shortening. There is also a shortage of systematic reviews and data synthesis to explain the association between telomere shortening and disease progression in individuals with IBD. We aimed to systematically review the association between telomere shortening and disease advancement in individuals with IBD to inform future studies. Methods and analysis: We will undertake a thorough search of the electronic database from the beginning until December 31, 2023. We will search the databases: MEDLINE/PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), VIP, Wanfang Database (Wanfang), CMB, Cochrane Library, Cochran Clinical Trials Registry, and the World Health Organization International Clinical Trials Registry Platform. Two reviewers will assess the discovered citations for eligibility based on the title and abstract before proceeding to the full-text and data extraction phases. These reviewers will debate and settle any conflicts that arise during the inclusion process; a third reviewer will settle any issues that remain. The validated data extraction form will be used to collect data for eligible research. The included studies will undergo a quality and bias check and will proceed meta-analysis. Discussion: This systematic review and meta-analysis will reveal a positive correlation between illness progression and telomere shortening in individuals with IBD, perhaps demonstrating three causal links between them. This study will conduct the first systematic review and meta-analysis examining the correlation between telomere shortening and illness advancement in individuals with IBD. Exploring the connection between these two situations can enhance the comprehension of the development and advancement of IBD. Systematic review registration: PROSPERO registration number: CRD42024501171. [ABSTRACT FROM AUTHOR]

Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome, caused by genetic mutations that principally affect telomere biology. Approximately 35% of cases remain uncharacterised at the genetic level. To explore the genetic landscape, we conducted genetic studies on a large collection of clinically diagnosed cases of DC as well as cases exhibiting features resembling DC, referred to as 'DC-like' (DCL). This led us to identify several novel pathogenic variants within known genetic loci and in the novel X-linked gene, POLA1. In addition, we have also identified several novel variants in POT1 and ZCCHC8 in multiple cases from different families expanding the allelic series of DC and DCL phenotypes. Functional characterisation of novel POLA1 and POT1 variants, revealed pathogenic effects on protein-protein interactions with primase, CTC1-STN1-TEN1 (CST) and shelterin subunit complexes, that are critical for telomere maintenance. ZCCHC8 variants demonstrated ZCCHC8 deficiency and signs of pervasive transcription, triggering inflammation in patients' blood. In conclusion, our studies expand the current genetic architecture and broaden our understanding of disease mechanisms underlying DC and DCL disorders. Synopsis: The evolving genetic landscape of inherited bone marrow failure syndrome dyskeratosis congenita reveals new pathogenic variants that broadens our understanding of current genetic and molecular mechanisms underlying this disorder. Several novel pathogenic variants within known susceptibility loci, as well as in the novel X-linked locus POLA1, are part of the evolving DC and DCL genetic landscape. Telomere maintenance is impacted by novel variants in POLA1 and POT1, while pervasive transcription and inflammation are caused by ZCCHC8 variants. Current knowledge on disease mechanisms beyond the regulation of long non-coding RNA TERC is extended by the clinical, genetic, and molecular similarity between DC and DCL cases. The evolving genetic landscape of inherited bone marrow failure syndrome dyskeratosis congenita reveals new pathogenic variants that broadens our understanding of current genetic and molecular mechanisms underlying this disorder. [ABSTRACT FROM AUTHOR]

Opsariichthys bidens is an endemic minnow, mainly distributed in China as an emerging aquaculture species. In this study, O. bidens collected from Yangzte River (YR), Pearl River (PR) and Qiantang River (QR) basins were used for karyotypic study and genome sequencing. Using PacBio long reads and Hi-C data, we assembled high-quality O. bidens genomes of 852.41 Mb (YR), 843.11 Mb (PR) and 840.94 Mb (QR) with scaffold N50 lengths of 21.01 Mb, 23.62 Mb and 24.75 Mb, respectively, of which 90.39%, 95.67% and 99.01% were anchored to 37, 38 and 39 chromosomes, respectively. 26,556 (YR), 25,036 (PR) and 26,283 (QR) protein-coding genes were predicted, respectively. The karyotype of O. bidens from YR, PR and QR were 2 N = 74 (6 m + 6sm + 4st + 58t), 2 N = 76 (4 m + 6sm + 4st + 62t) and 2 N = 78 (4 m + 4sm + 4st + 66t), respectively. Collinearity analysis and telomere predictions indicated that the observed chromosomal evolution was driven by Robertsonian translocation. These genome assemblies facilitate cryptic species determination, evolutionary study and genetic breeding of genus Opsariichthys. [ABSTRACT FROM AUTHOR]

Cancer cells have the ability to undergo an unlimited number of cell divisions, which gives them immortality. Thus, the cancer cell can extend the length of its telomeres, allowing these cells to divide unlimitedly and avoid entering the state of senescence or cellular apoptosis. One of the main effects of photobiomodulation (PBM) is the increase in the production of adenosine triphosphate (ATP) and free radicals, mainly reactive oxygen species (ROS). Existent data indicates that high levels of ROS can cause shortening and dysfunctional telomeres. Therefore, a better understanding of the effects induced by PBM on cancer cell telomere maintenance is needed. This work aimed to evaluate the effects of low-power red laser (658 nm) and blue LED (470 nm) on the TRF1 and TRF2 mRNA levels and telomere length in human breast cancer cells. MCF-7 and MDA-MB-231 cells were irradiated with a low-power red laser (69 J cm-2, 0.77 W/cm-2) and blue LED (482 J cm-2, 5.35 W/cm-2), alone or in combination, and the relative mRNA levels of the genes and telomere length were assessed by quantitative reverse transcription polymerase chain reaction. The results suggested that exposure to certain red laser and blue LED fluences decreased the TRF1 and TRF2 mRNA levels in both human breast cancer cells. Telomere length was increased in MCF-7 cells after exposure to red laser and blue LED. However, telomere length in MDA-MB-231 was shortened after exposure to red laser and blue LED at fluences evaluated. Our research suggests that photobiomodulation induced by red laser and low-power blue LED could alter telomere maintenance and length. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: To verify whether shorter telomere length is associated with anorexia of ageing in community‐dwelling older people. Methods: Conducted as a cross‐sectional investigation, the study enrolled 448 participants residing in an urban area of a municipality in Brazil. Relative telomere length in blood samples was measured using quantitative polymerase chain reaction (qPCR), whereas the presence of anorexia of ageing was determined using the Simplified Appetite Nutritional Questionnaire. Data analysis employed multiple logistic regression. Results: Among the 448 older individuals surveyed, 70.69% were female, and the predominant age bracket ranged from 60 to 69 years (45.08%). Approximately 25% exhibited the shortest telomeric length, with a corresponding anorexia of ageing prevalence of 41.16%. Older individuals with diminished telomere lengths displayed an increased likelihood of experiencing anorexia of ageing (odds ratio [OR] = 1.92; 95% confidence interval [CI] = 1.12–3.29), independent of factors such as gender, age group, depressive symptoms, pain and performance in basic daily life activities. Conclusions: The observed association between anorexia of ageing and a telomeric biomarker underscores the imperative to meticulously evaluate the nutritional dimensions of older people, with a view to implementing interventions that may enhance their overall health status. Highlights: Older people with shorter telomere length are more likely to have anorexia of ageing.The association between shorter telomere length and anorexia of ageing is independent of sex, age group, depressive symptoms, pain and performance in basic activities of daily living. [ABSTRACT FROM AUTHOR]

Telomeres—special DNA–protein structures at the ends of linear eukaryotic chromosomes—define the proliferation potential of cells. Extremely short telomeres promote a DNA damage response and cell death to eliminate cells that may have accumulated mutations after multiple divisions. However, telomere elongation is associated with the increased proliferative potential of specific cell types, such as stem and germ cells. This elongation can be permanent in these cells and is activated temporally during immune response activation and regeneration processes. The activation of telomere lengthening mechanisms is coupled with increased proliferation and the cells' need for energy and building resources. To obtain the necessary nutrients, cells are capable of finely regulating energy production and consumption, switching between catabolic and anabolic processes. In this review, we focused on the interconnection between metabolism programs and telomere lengthening mechanisms during programmed activation of proliferation, such as in germ cell maturation, early embryonic development, neoplastic lesion growth, and immune response activation. It is generally accepted that telomere disturbance influences biological processes and promotes dysfunctionality. Here, we propose that metabolic conditions within proliferating cells should be involved in regulating telomere lengthening mechanisms, and telomere length may serve as a marker of defects in cellular functionality. We propose that it is possible to reprogram metabolism in order to regulate the telomere length and proliferative activity of cells, which may be important for the development of approaches to regeneration, immune response modulation, and cancer therapy. However, further investigations in this area are necessary to improve the understanding and manipulation of the molecular mechanisms involved in the regulation of proliferation, metabolism, and aging. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Telomeres, repetitive sequences located at the extremities of chromosomes, play a pivotal role in sustaining chromosomal stability. Telomerase is a complex enzyme that can elongate telomeres by appending telomeric repeats to chromosome ends and acts as a critical factor in telomere dynamics. The gradual shortening of telomeres over time is a hallmark of cellular senescence and cellular death. Notably, telomere shortening appears to result from the complex interplay of two primary mechanisms: telomere shelterin complexes and telomerase activity. The intricate interplay of genetic, environmental, and lifestyle influences can perturb telomere replication, incite oxidative stress damage, and modulate telomerase activity, collectively resulting in shifts in telomere length. This age-related process of telomere shortening plays a considerable role in various chronic inflammatory and oxidative stress conditions, including cancer, cardiovascular disease, and rheumatic disease. Existing evidence has shown that abnormal telomere shortening or telomerase activity abnormalities are present in the pathophysiological processes of most rheumatic diseases, including different disease stages and cell types. The impact of telomere shortening on rheumatic diseases is multifaceted. This review summarizes the current understanding of the link between telomere length and rheumatic diseases in clinical patients and examines probable telomere shortening in peripheral blood mononuclear cells and histiocytes. Therefore, understanding the intricate interaction between telomere shortening and various rheumatic diseases will help in designing personalized treatment and control measures for rheumatic disease. [ABSTRACT FROM AUTHOR]

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 (β: 0.29; 95%CI: 0.12 to 0.44; P < 0.001) and the Global Cognitive Function domain (β: 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 (β: 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. [ABSTRACT FROM AUTHOR]

A telomere is a repetitive DNA sequence located at the end of human chromosomes, and its length shortens with age. Research has demonstrated that estrogen is associated with the aging of various types of cells, including brain, muscle, and bone cells. This study explored the cross-sectional association between estrogen usage and telomere length, utilizing data from the US National Health and Nutrition Examination Survey (NHANES) 1999-2002. The final number of participants included in this study was 491. This study's bivariate Rao-Scott χ2 test revealed a significant association between telomere length and gender (p < 0.01). Females have longer telomeres than males, indicated by a rate ratio of 1.72. A positive relationship between estrogen usage and telomere length was observed among female participants, yielding a rate ratio of 1.44. The mosaic diagram and Pearson residuals confirmed the statistical significance of this difference (p < 0.001). This suggests that estrogen administration may preserve telomeres and contribute to healthy aging. In conjunction with the findings from the literature, this study supports the need for further investigations into the effects of estrogen administration on telomere length. [ABSTRACT FROM AUTHOR]

Life history theory predicts increased parental investment comes with fitness costs, often expressed as negative effects on survival and future reproduction. To better understand the costs of reproduction and life history trade‐offs, we evaluated calcium supplementation at a high‐elevation site in Colorado as a novel approach to experimentally alter reproductive investment in nesting female Tachycineta bicolor (tree swallow). Calcium is a nutrient critical to avian reproduction as the intake of natural calcium is essential for egg production, embryo development, and nestling growth. Altering calcium availability exclusively during the breeding season allowed examination of individual biological responses to experimental modification of reproduction, as well as the reproductive costs associated with egg production and laying an entire clutch. As a functional endpoint and proxy for fitness and longevity, telomere length was measured at the beginning and end of each breeding season. Telomeres—protective "caps" at the ends of chromosomes—have been shown to shorten with aging and a variety of stressors, including higher reproductive output. Results demonstrate that tree swallow mothers supplemented with calcium during the breeding season experience higher reproductive output and produce offspring with longer telomeres, which came at the cost of relatively shorter telomeres during the reproductive season. These findings provide additional support for reproductive trade‐offs, and also challenge previous calcium supplementation studies that suggest excess calcium reduces the cost of reproduction. [ABSTRACT FROM AUTHOR]

Background/Objectives: Emerging evidence suggests that patients suffering from COVID-19 may experience neurocognitive symptoms. Furthermore, other studies indicate a probable association between leukocyte telomere length (LTL) and neurocognitive changes in subjects with post-COVID-19 condition. Our study was designed to determine the correlation between telomere length and cognitive changes in post-COVID-19 subjects. Methods: This study included 256 subjects, categorized based on SARS-CoV-2 infection from 2020 to 2023. In addition, subjects with a psychiatric diagnosis were considered. Moreover, the MoCA and MMSE scales were applied. Telomere length was determined using a polymerase chain reaction, and statistical analysis was employed using ANOVA and X2 tests. Results: We identified a decrease in LTL in individuals with post-COVID-19 conditions compared to those without SARS-CoV-2 infection (p ≤ 0.05). However, no association was found between LTL and cognitive impairment in the subjects post-COVID-19. Conclusions: The findings suggest that LTL is affected by SARS-CoV-2 infection. Nonetheless, this important finding requires further research by monitoring neurological changes in subjects with post-COVID condition. [ABSTRACT FROM AUTHOR]

Karyotype divergence may strongly affect the degree of hybridization between species. Western Palearctic slow worms (Anguis) are legless lizards forming different types of secondary contact zones. To identify the level of chromosomal variation in slow worms, we examined karyotype in multiple populations of all species except one and Pseudopus apodus as an outgroup. We applied conventional and molecular cytogenetic methods and whole-chromosome painting using macrochromosome probes from Varanus komodoensis to interpret results within the evolutionary framework of the common clade Anguiformes. All Anguis species and P. apodus have conserved karyotype structures composed of 44 chromosomes. Despite the conserved chromosome morphology, the phylogenetically oldest Anguis cephallonica living in partial sympatry with Anguis graeca , and parapatric Anguis colchica vs. Anguis fragilis exhibit distinct patterns of constitutive heterochromatin distribution and telomeric repeat accumulation. In contrast, the sister species A. colchica and A. graeca living in allopatry display highly similar karyotype features. Our findings thus indicate karyotype stasis in Anguis and Pseudopus for > 20 Myr, with fixed species-specific differences present in sympatric and parapatric species. These differences in repetitive DNA patterns may play a role as intrinsic factors co-maintaining species divergence. They may also be used as cytotaxonomic markers to identify slow worm species in practice. [ABSTRACT FROM AUTHOR]

Iron is essential for organ system development, DNA replication, and metabolic processes. Excessive iron storage can lead to oxidative stress, which can cause age-related conditions. Telomere length is a biomarker for aggregate oxidative stress and biological ageing, linked to age-related diseases and ailments. High body iron status may cause oxidative stress, leading to the loss of telomeric sequences. However, no research has been conducted on the relationship between telomere length and iron profile in South Canara residents. Understanding this association can help devise protocols to recover neonatal outcomes. The aim of this study is to determine the relationship between iron profile status and telomere length in cord blood. 73 cord blood sample was collected at the time of birth from participants visiting the outpatient Department of Obstetrics and Gynaecology. Demographic, anthropometric information and baseline characteristics of the consented study participants was obtained. Iron profile status and Telomere length was assessed by standardised protocol. In this study, positive association was observed between serum ferritin and rTL, groups adjusted based on birth mode and diagnosis of hyperbilirubinemia also showed a positive association between rTL and ferritin, while negative association between rTL and serum iron in cord blood of neonates birthed through LSCS. In conclusion, this study found significant relationships between relative telomere length, telomerase activity and iron profile status in cord blood. In conclusion, compared to relative telomere length, Telomerase is strongly associated with iron profile in the cord blood. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) has been receiving a lot of attention from scientists and clinicians because it is an extremely common clinical condition. Due to its special hemodynamic changes, AF has a high rate of disability and mortality. So far, although AF has some therapeutic means, it is still an incurable disease because of its complex risk factors and pathophysiologic mechanisms, which is a difficult problem for global public health. Age is an important independent risk factor for AF, and the incidence of AF increases with age. To date, there is no comprehensive review on aging‐associated AF. In this review, we systematically discuss the pathophysiologic evidence for aging‐associated AF, and in particular explore the pathophysiologic mechanisms of mitochondrial dysfunction, telomere attrition, cellular senescence, disabled macroautophagy, and gut dysbiosis involved in recent studies with aging‐associated AF. We hope that by exploring the various dimensions of aging‐associated AF, we can better understand the specific relationship between age and AF, which may be crucial for innovative treatments of aging‐associated AF. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer affects millions worldwide, with gastrointestinal cancers being notably common. This review explores the potential of telomeres and telomerase as biomarkers for diagnosing and predicting these cancers. Telomeres are protective caps at chromosome ends that shorten with cell division, while telomerase helps extend them. Changes in these markers could indicate cancer risk and progression. Despite efforts to prevent cancer through lifestyle changes, gastrointestinal cancers such as colorectal and gastric cancer remain prevalent. Current detection methods like endoscopy are invasive, driving interest in non-invasive alternatives. By consolidating research on telomere length and telomerase activity, this review aims to highlight how these biomarkers could enhance early diagnosis and monitoring. Understanding these mechanisms better could lead to improved diagnostic tools and therapeutic strategies, potentially refining how gastrointestinal cancers are managed and improving patient outcomes. 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. [ABSTRACT FROM AUTHOR]

Background and Objectives: The association between neurological disability, prognosis, and telomere length (TL) in patients with stroke has been investigated in various ways. However, analysis of the type of stroke and ischemic stroke subgroups is limited. In this study, we aimed to determine the association between TL and neurological disability according to stroke type. Materials and Methods: This prospective study included patients with stroke who visited a single-center emergency department (ED) between January 2022 and December 2023. The association between TL and neurological disabilities, using the Modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS), was evaluated according to the patient's stroke type and subgroup of ischemic stroke. Multivariate analysis was performed to determine the association between neurological disabilities in patients with ischemic stroke and the subgroups. Results: A total of 271 patients with stroke were enrolled. The NIHSS score was found to be higher at the time of ED visit (adjusted odds ratio [OR], 5.23; 95% confidence interval [CI], 1.59–17.2, p < 0.01) and 1 day later (adjusted OR, 7.78; 95% CI, 1.97–30.70, p < 0.01) in the ischemic stroke group with a short TL. In the other determined etiology (OD) or undetermined etiology (UD) group, the NIHSS was higher in the short TL group at the ED visit (adjusted OR, 7.89; 95% CI, 1.32–47.25, p = 0.02) and 1 day after (adjusted OR, 7.02; 95% CI, 1.14–43.47, p = 0.04). Conclusions: TL is associated with neurological disability in early ischemic stroke and is prominent in the UD and OD subgroups. [ABSTRACT FROM AUTHOR]

Telomere length is a putative biomarker of aging and is associated with multiple age-related diseases. There are limited data on the landscape of rare genetic variations in telomere length. Here, we systematically characterize the rare variant associations with leukocyte telomere length (LTL) through exome-wide association study (ExWAS) among 390,231 individuals in the UK Biobank. We identified 18 robust rare-variant genes for LTL, most of which estimated effects on LTL were significant (> 0.2 standard deviation per allele). The biological functions of the rare-variant genes were associated with telomere maintenance and capping and several genes were specifically expressed in the testis. Three novel genes (ASXL1, CFAP58, and TET2) associated with LTL were identified. Phenotypic association analyses indicated significant associations of ASXL1 and TET2 with cancers, age-related diseases, blood assays, and cardiovascular traits. Survival analyses suggested that carriers of ASXL1 or TET2 variants were at increased risk for cancers; diseases of the circulatory, respiratory, and genitourinary systems; and all-cause and cause-specific deaths. The CFAP58 carriers were at elevated risk of deaths due to cancers. Collectively, the present whole exome sequencing study provides novel insights into the genetic landscape of LTL, identifying novel genes associated with LTL and their implications on human health and facilitating a better understanding of aging, thus pinpointing the genetic relevance of LTL with clonal hematopoiesis, biomedical traits, and health-related outcomes. [ABSTRACT FROM AUTHOR]

Cellular senescence is a hallmark of aging characterized by irreversible growth arrest and functional decline. Progressive telomeric DNA shortening in dividing somatic cells, programmed during development, leads to critically short telomeres that trigger replicative senescence and thereby contribute to aging. Therefore, protecting telomeres from DNA damage is essential in order to avoid entry into senescence and organismal aging. In several organisms, including mammals, telomeres are protected by a protein complex named shelterin that prevents DNA damage at the chromosome ends through the specific function of its subunits. Here, we reveal that the nuclear protein levels of shelterin components TRF1 and TRF2 decline in fibroblasts reaching senescence. Notably, we identify α-terpineol as an activator that effectively enhances TRF1 and TRF2 levels in a telomerase-independent manner, counteracting the senescence-associated decline in these crucial proteins. Moreover, α-terpineol ameliorates the cells' response to oxidative DNA damage, particularly at the telomeric regions, thus preserving telomere length and delaying senescence. More importantly, our findings reveal the significance of the PI3K/AKT pathway in the regulation of shelterin components responsible for preserving telomere integrity. In conclusion, this study deepens our understanding of the molecular pathways involved in senescence-associated telomere dysfunction and highlights the potential of shelterin components to serve as targets of therapeutic interventions, aimed at promoting healthy aging and combating age-related diseases. [ABSTRACT FROM AUTHOR]

Aging, an independent risk factor for cardiometabolic diseases, refers to a progressive deterioration in physiological function, characterized by 12 established hallmarks. Vascular aging is driven by endothelial dysfunction, telomere dysfunction, oxidative stress, and vascular inflammation. This study investigated whether aged gut microbiome promotes vascular aging and metabolic impairment. Fecal microbiome transfer (FMT) was conducted from aged (>75 weeks old) to young C57BL/6 mice (8 weeks old) for 6 weeks. Wire myography was used to evaluate endothelial function in aortas and mesenteric arteries. ROS levels were measured by dihydroethidium (DHE) staining and lucigenin-enhanced chemiluminescence. Vascular and intestinal telomere function, in terms of relative telomere length, telomerase reverse transcriptase expression and telomerase activity, were measured. Systemic inflammation, endotoxemia and intestinal integrity of mice were assessed. Gut microbiome profiles were studied by 16S rRNA sequencing. Some middle-aged mice (40–42 weeks old) were subjected to chronic metformin treatment and exercise training for 4 weeks to evaluate their anti-aging benefits. Six-week FMT impaired glucose homeostasis and caused vascular dysfunction in aortas and mesenteric arteries in young mice. FMT triggered vascular inflammation and oxidative stress, along with declined telomerase activity and shorter telomere length in aortas. Additionally, FMT impaired intestinal integrity, and triggered AMPK inactivation and telomere dysfunction in intestines, potentially attributed to the altered gut microbial profiles. Metformin treatment and moderate exercise improved integrity, AMPK activation and telomere function in mouse intestines. Our data highlight aged microbiome as a mechanism that accelerates intestinal and vascular aging, suggesting the gut-vascular connection as a potential intervention target against cardiovascular aging and complications. [ABSTRACT FROM AUTHOR]

Telomeres, the ends of eukaryotic linear chromosomes, are composed of repeated DNA sequences and specialized proteins, with the conserved telomeric Cdc13/CTC1-Stn1-Ten1 (CST) complex providing chromosome stability via telomere end protection and the regulation of telomerase accessibility. In this study, SIZ1, coding for a SUMO E3 ligase, and TOP2 (a SUMO target for Siz1 and Siz2) were isolated as extragenic suppressors of Saccharomyces cerevisiae CST temperature-sensitive mutants. ten1-sz, stn1-sz and cdc13-sz mutants were isolated next due to being sensitive to intracellular Siz1 dosage. In parallel, strong negative genetic interactions between mutants of CST and septins were identified, with septins being noticeably sumoylated through the action of Siz1. The temperature-sensitive arrest in these new mutants of CST was dependent on the G2/M Mad2-mediated and Bub2-mediated spindle checkpoints as well as on the G2/M Mec1-mediated DNA damage checkpoint. Our data suggest the existence of yet unknown functions of the telomeric Cdc13-Stn1-Ten1 complex associated with mitotic spindle positioning and/or assembly that could be further elucidated by studying these new ten1-sz, stn1-sz and cdc13-sz mutants. [ABSTRACT FROM AUTHOR]

Objectives To investigate the potential role of shelterin dysfunction in naïve CD4+ T cells in the pathogenesis of Behçet's disease (BD). Methods Naïve CD4+ T cells were isolated from 40 BD patients and 40 sex- and age-matched healthy controls (HC). Senescent profiles, shelterin subunits expression, telomere length, telomerase activity and critical DNA damage response (DDR) were evaluated. Telomere repeat factor-2 (TRF2) silencing was conducted for further validation. Results Compared with HC, BD patients had significantly decreased naïve CD4+ T cells, increased cell apoptosis, senescence, and productions of TNF-α and IFN-γ upon activation. Notably, BD naïve CD4+ T cells had shortened telomere, impaired telomerase activity, and expressed lower levels of shelterin subunits TRF2, TRF1- and TRF2-Interacting Nuclear Protein 2 (TIN2) and Repressor/Activator Protein 1 (RAP1). Furthermore, BD naïve CD4+ T cells exhibited significantly increased DDR, evidenced by elevated phosphorylated ataxia telangiectasia (AT) mutated (pATM), phosphorylated p53 (pp53) and p21. Finally, TRF2 silencing markedly upregulated DDR, apoptosis and proinflammatory cytokines production in HC naïve CD4+ T cells. Conclusion Our study demonstrated that TRF2 deficiency in BD naïve CD4+ T cells promoted cell apoptosis and senescence, leading to proinflammatory cytokines overproduction. Therefore, restoring TRF2 might be a promising therapeutic strategy for BD. [ABSTRACT FROM AUTHOR]

In this paper, we have performed an in-depth study of the complete set of the satellite DNA (satDNA) families (i.e. the satellitomes) in the genome of two barley species of agronomic value in a breeding framework, H. chilense (H1 and H7 accessions) and H. vulgare (H106 accession), which can be useful tools for studying chromosome associations during meiosis. The study has led to the analysis of a total of 18 satDNA families in H. vulgare, 25 satDNA families in H. chilense (accession H1) and 27 satDNA families in H. chilense (accession H7) that constitute 46 different satDNA families forming 36 homology groups. Our study highlights different important contributions of evolutionary and applied interests. Thus, both barley species show very divergent satDNA profiles, which could be partly explained by the differential effects of domestication versus wildlife. Divergence derives from the differential amplification of different common ancestral satellites and the emergence of new satellites in H. chilense, usually from pre-existing ones but also random sequences. There are also differences between the two H. chilense accessions, which support genetically distinct groups. The fluorescence in situ hybridization (FISH) patterns of some satDNAs yield distinctive genetic markers for the identification of specific H. chilense or H. vulgare chromosomes. Some of the satellites have peculiar structures or are related to transposable elements which provide information about their origin and expansion. Among these, we discuss the existence of different (peri)centromeric satellites that supply this region with some plasticity important for centromere evolution. These peri(centromeric) satDNAs and the set of subtelomeric satDNAs (a total of 38 different families) are analyzed in the framework of breeding as the high diversity found in the subtelomeric regions might support their putative implication in chromosome recognition and pairing during meiosis, a key point in the production of addition/substitution lines and hybrids.Key message: Several satDNAs have been identified in the subtelomeres of wild and cultivated barley species that might contribute to the specificity of these distal chromosome regions during homologous recognition and pairing in meiosis. [ABSTRACT FROM AUTHOR]

Mammalian DNA replication relies on various DNA helicase and nuclease activities to ensure accurate genetic duplication, but how different helicase and nuclease activities are properly directed remains unclear. Here, we identify the ubiquitin-specific protease, USP50, as a chromatin-associated protein required to promote ongoing replication, fork restart, telomere maintenance, cellular survival following hydroxyurea or pyridostatin treatment, and suppression of DNA breaks near GC-rich sequences. We find that USP50 supports proper WRN-FEN1 localisation at or near stalled replication forks. Nascent DNA in cells lacking USP50 shows increased association of the DNA2 nuclease and RECQL4 and RECQL5 helicases and replication defects in cells lacking USP50, or FEN1 are driven by these proteins. Consequently, suppression of DNA2 or RECQL4/5 improves USP50-depleted cell resistance to agents inducing replicative stress and restores telomere stability. These data define an unexpected regulatory protein that promotes the balance of helicase and nuclease use at ongoing and stalled replication forks. Mammalian DNA replication relies on various helicases and nucleases to ensure accurate genetic duplication, but how these enzymes are properly directed is unclear. Here, the authors identify USP50 as a key protein for promoting ongoing replication, restarting stalled forks, maintaining telomeres, and ensuring cell survival. [ABSTRACT FROM AUTHOR]

Telomere lengths and telomere dynamics can correlate with lifespan, behaviour and individual quality. Such relationships have spurred interest in understanding variation in telomere lengths and their dynamics within and between populations. Many studies have identified how environmental processes can influence telomere dynamics, but the role of genetic variation is much less well characterized. To provide a novel perspective on how telomeric variation relates to genetic variability, we longitudinally sampled individuals across a narrow hybrid zone (n = 127 samples), wherein two Manacus species characterized by contrasting genome‐wide heterozygosity interbreed. We measured individual (n = 66) and population (n = 3) differences in genome‐wide heterozygosity and, among hybrids, amount of genetic admixture using RADseq‐generated SNPs. We tested for population differences in telomere lengths and telomere dynamics. We then examined how telomere lengths and telomere dynamics covaried with genome‐wide heterozygosity within populations. Hybrid individuals exhibited longer telomeres, on average, than individuals sampled in the adjacent parental populations. No population differences in telomere dynamics were observed. Within the parental population characterized by relatively low heterozygosity, higher genome‐wide heterozygosity was associated with shorter telomeres and higher rates of telomere shortening—a pattern that was less apparent in the other populations. All of these relationships were independent of sex, despite the contrasting life histories of male and female manakins. Our study highlights how population comparisons can reveal interrelationships between genetic variation and telomeres, and how naturally occurring hybridization and genome‐wide heterozygosity can relate to telomere lengths and telomere dynamics. [ABSTRACT FROM AUTHOR]

Simple Summary: Telomere length (TL) may influence the carcinogenesis process. Short telomeres lead to genomic instability, which is an important event in tumor initiation, while long telomeres may promote cell division and immortality influencing tumor promotion/progression. Despite the numerous observational epidemiological studies available, the association between TL in leukocytes (LTL) and lung cancer risk is currently still uncertain. Therefore, we conducted this systematic review and meta-analysis of prospective studies to summarize the evidence and derive a more accurate estimate of the effect of LTL on lung cancer occurrence. Longer LTL could be a marker to identify subjects at high risk of developing lung cancer. This may help to focus secondary prevention (screening) on specific groups of subjects. Although numerous epidemiological studies are available, the relationship between leukocyte telomere length (LTL) and lung cancer risk is still controversial. This systematic review and meta-analysis, performed according to the PRISMA statement and MOOSE guidelines, aims to summarize the evidence and calculate the risk of lung cancer associated with LTL. The literature search was performed on PubMed, Web of Science, and Scopus databases through May 2024. A random-effects model was used to calculate the pooled risk. Heterogeneity was assessed using I2 and Cochran's Q statistic. Begg's and Egger's tests were used to detect publication bias. Based on 8055 lung cancer cases and 854,653 controls (nine prospective studies), longer LTL was associated with a significant 42% increment in all types of lung cancer risk (OR 1.42, 95% CI 1.24–1.63). The effect was even more evident for adenocarcinomas (OR 1.98, 95% CI 1.69–2.31), while no association was observed for squamous cell carcinoma (OR 0.87, 95% CI 0.72–1.06). Significantly, no association was found for current smokers (OR 1.08, 95% CI 0.90–1.30), while it remained high for both never-smokers (OR 1.92, 95% CI 1.62–2.28) and former smokers (OR 1.34, 95% CI 1.11–1.62). No significant publication bias was evidenced. Longer LTL is associated with an increment in lung cancer risk particularly in never-smoker subjects. [ABSTRACT FROM AUTHOR]

Shortening of telomere length (TL) is correlated with many age-related disorders and is a hallmark of biological aging. This study used proteome-wide Mendelian randomization to identify the protein biomarkers associated with telomere length. Protein quantitative trait loci (pQTL) were derived from two studies, the deCODE Health study (4907 plasma proteins) and the UK Biobank Pharma Proteomics Project (2923 plasma proteins). Summary data from genome-wide association studies (GWAS) for TL were obtained from the UK Biobank (472,174 cases) and GWAS Catalog (418,401 cases). The association between proteins and TL was further assessed using colocalization and summary data-based Mendelian randomization (SMR) analyses. The protein–protein network, druggability assessment, and phenome-wide MR were used to further evaluate the potential biological effects, druggability, and safety of the target proteins. Proteome-wide MR analysis identified 22 plasma proteins that were causally associated with telomere length. Five of these proteins (APOE, SPRED2, MAX, RALY, and PSMB1) had the highest evidence of association with TL and should be prioritized. This study revealed telomere length-related protein biomarkers, providing new insights into the development of new treatment targets for chronic diseases and anti-aging intervention strategies. [ABSTRACT FROM AUTHOR]

This document discusses the health effects of low-dose-rate radiation exposure with cumulative doses. It challenges the linear no-threshold (LNT) paradigm, which asserts that any dose of radiation carries some risk of harm, and argues that low doses of radiation may actually have beneficial effects and stimulate protective biological responses. The document highlights research on animals and populations exposed to radiation, which suggests a possible threshold or hormetic response. It emphasizes the need for further research on low-dose-rate radiation exposure with cumulative doses to inform policymaking and reduce public anxiety. The document also mentions the consequences of improper evacuation during nuclear accidents, particularly for vulnerable populations. Overall, the document suggests that investigating the health effects of low-dose-rate irradiation with cumulative threshold doses is a promising area of research with significant scientific, social, and economic value. [Extracted from the article]

The "Mlx" and "Myc" transcription factor networks cross‐communicate and share many common gene targets. Myc's activity depends upon its heterodimerization with Max, whereas the Mlx Network requires that the Max‐like factor Mlx associate with the Myc‐like factors MondoA or ChREBP. The current work demonstrates that body‐wide Mlx inactivation, like that of Myc, accelerates numerous aging‐related phenotypes pertaining to body habitus and metabolism. The deregulation of numerous aging‐related Myc target gene sets is also accelerated. Among other functions, these gene sets often regulate ribosomal and mitochondrial structure and function, genomic stability, and aging. Whereas "MycKO" mice have an extended lifespan because of a lower cancer incidence, "MlxKO" mice have normal lifespans and a higher cancer incidence. Like Myc, the expression of Mlx, MondoA, and ChREBP and their control over their target genes deteriorate with age in both mice and humans. Collectively, these findings underscore the importance of lifelong and balanced cross‐talk between the two networks to maintain proper function and regulation of the many factors that can affect normal aging. [ABSTRACT FROM AUTHOR]

Lettuce (Lactuca sativa L., Asteraceae) is one of the most important vegetable crops, known for its various horticultural types and significant morphological variation. The first reference genome of lettuce, a crisphead type (L. sativa var. capitata cv. Salinas), was previously released. Here, we reported a near-complete chromosome-level reference genome for looseleaf lettuce (L. sativa var. crispa). PacBio high-fidelity sequencing, Oxford Nanopore, and Hi-C technologies were employed to produce genome assembly. The final assembly is 2.59 Gb in length with a contig N50 of 205.47 Mb, anchored onto nine chromosomes, containing 14 recognizable telomeres and only 11 gaps. Repetitive sequences account for 77.11% of the genome, and 41,375 protein-coding genes were predicted, with 99.10% of these assigned functional annotations. This chromosome-level genome enriched genomic resources for various horticultural types of lettuce and will facilitate the characterization of morphological variation and genetic improvement in lettuce. [ABSTRACT FROM AUTHOR]

Introduction: Alternative lengthening of telomeres (ALT) occurs in sarcomas and ALT cancers share common mechanisms of therapy resistance or sensitivity. Telomeric DNA C-circles are self-primed circular telomeric repeats detected with a PCR assay that provide a sensitive and specific biomarker exclusive to ALT cancers. We have previously shown that 23% of high-risk neuroblastomas are of the ALT phenotype. Here, we investigate the frequency of ALT in Ewing's family sarcoma (EFS), rhabdomyosarcoma (RMS), and osteosarcoma (OS) by analyzing DNA from fresh frozen primary tumor samples utilizing the real-time PCR C-circle Assay (CCA). Methods: We reviewed prior publications on ALT detection in pediatric sarcomas. DNA was extracted from fresh frozen primary tumors, fluorometrically quantified, C-circles were selectively enriched by isothermal rolling cycle amplification and detected by real-time PCR. Results: The sample cohort consisted of DNA from 95 EFS, 191 RMS, and 87 OS primary tumors. One EFS and 4 RMS samples were inevaluable. Using C-circle positive (CC+) cutoffs previously defined for high-risk neuroblastoma, we observed 0 of 94 EFS, 5 of 187 RMS, and 62 of 87 OS CC+ tumors. Conclusions: Utilizing the ALT-specific CCA we observed ALT in 0% of EFS, 2.7% of RMS, and 71% of OS. These data are comparable to prior studies in EFS and OS using less specific ALT markers. The CCA can provide a robust and sensitive means of identifying ALT in sarcomas and has potential as a companion diagnostic for ALT targeted therapeutics. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to investigate the causal effect and potential mechanisms between telomere length and abdominal aortic aneurysm (AAA). Methods: Summary statistics of telomere length and AAA were derived from IEU open genome-wide association studies and FinnGen R9, respectively. Bidirectional Mendelian randomization (MR) analysis was conducted to reveal the causal relationship between AAA and telomere length. Three transcriptome datasets were retrieved from the Gene Expression Omnibus database and telomere related genes was down-loaded from TelNet. The overlapping genes of AAA related differentially expressed genes (DEGs), module genes, and telomere related genes were used for further investigation. Telomere related diagnostic biomarkers of AAA were selected with machine learning algorisms and validated in datasets and murine AAA model. The correlation between biomarkers and immune infiltration landscape was established. Results: Telomere length was found to have a suggestive negative associations with AAA [IVW, OR 95%CI = 0.558 (0.317-0.701), P < 0.0001], while AAA showed no suggestive effect on telomere length [IVW, OR 95%CI = 0.997 (0.990-1.004), P = 0.4061]. A total of 40 genes was considered as telomere related DEGs of AAA. PLCH2, PRKCQ, and SMG1 were selected as biomarkers after multiple algorithms and validation. Immune infiltration analysis and single cell mRNA analysis revealed that PLCH2 and PRKCQ were mainly expressed on T cells, while SMG1 predominantly expressed on T cells, B cells, and monocytes. Murine AAA model experiments further validated the elevated expression of biomarkers. Conclusion: We found a suggestive effect of telomere length on AAA and revealed the potential biomarkers and immune mechanism of telomere length on AAA. This may shed new light for diagnosis and therapeutics on AAA [ABSTRACT FROM AUTHOR]

Background: Psychological and trauma-related factors are associated with many diseases and mortality. However, a comprehensive assessment of the association between psycho-trauma exposures and aging acceleration is currently lacking. Methods: Using data from 332,359 UK Biobank participants, we calculated biological aging acceleration, indexed by the presence of leukocyte telomere length (LTL) deviation (i.e., the difference between genetically determined and observed LTL > 0). The acceleration of facial aging (i.e., looking older than the chronological age) was assessed using a self-report question. Then, we estimated the associations of each psycho-trauma factor with biological and facial aging acceleration, using logistic regression models adjusted for multiple important covariates. Furthermore, restricted to 99,180 participants with complete psychological and trauma-related data, we identified clusters of individuals with distinct psycho-trauma patterns using the latent class analysis method and assessed their associations with aging acceleration using similar models. Results: We observed most of the studied psycho-trauma factors were associated with biological and facial aging acceleration. Compared to the "Absence of trauma and psychopathology" cluster, the "adverse childhood experiences (ACEs) with psychopathology" cluster showed strong associations with those aging measurements (odds ratio [OR] = 1.13 [1.05 − 1.23] for biological and 1.52 [1.18 − 1.95] for facial aging acceleration), while no such association was observed for the "ACEs without psychopathology" cluster (1.04 [0.99 − 1.09] and 1.02 [0.84 − 1.24]. Conclusions: Our study demonstrated significant associations of psycho-trauma factors with both biological and facial aging acceleration. The differential aging consequences observed among ACEs exposed individuals with and without psychopathology prompt interventions aimed to improve individuals' psychological resilience to prevent aging acceleration. [ABSTRACT FROM AUTHOR]