Search Results (655)

Leukocyte telomere length (LTL) has been proposed as a molecular marker of biological aging reflecting cumulative cellular stress and replicative senescence. Multimorbidity represents a major challenge in aging populations and reflects the progressive accumulation of chronic diseases. However, the relationship between LTL and multimorbidity burden remains incompletely understood. We investigated the association between LTL and multimorbidity burden, assessed using Cumulative Illness Rating Scale (CIRS) indices, in a cohort of older nursing home residents. Sex-stratified analyses were performed to explore potential biological heterogeneity. In multivariate analyses, shorter LTL was significantly associated with higher multimorbidity burden among women, particularly when considering severity- and comorbidity-weighted CIRS indices [False discovery rate-adjusted q-values (qFDR < 0.01)], whereas no significant associations were observed in men. Adjustment for functional status partially attenuated but did not eliminate these associations. Organ-specific analyses indicated that these associations in women were primarily driven by cardiovascular, respiratory, gastrointestinal, and genitourinary domains, systems commonly characterized by chronic inflammatory and oxidative stress processes that may promote telomere attrition. Overall, these findings support a sex-specific relationship between telomere dynamics and clinically relevant multimorbidity patterns in very old adults. LTL may reflect biologically meaningful aspects of disease severity and systemic stress regulation rather than merely the accumulation of diagnoses. Full article

Background: Exposure of pregnant women to stress and endocrine-disrupting chemicals (EDCs) during pregnancy can have a substantial impact on mother and infant health. We investigated the concentrations of EDCs, such as parabens (PBs) and triclosan (TCS), as well as stress hormones (cortisone and cortisol), across pregnancy trimesters and examined their associations with maternal average telomere length (TL). Methods: Hair samples from 49 postpartum women were analyzed using liquid chromatography–mass spectrometry (LC-MS) to quantify EDCs and stress hormone concentrations. Results: The mean methyl paraben concentrations in the hair of postpartum women were prevalent across all pregnancy trimesters, while butyl paraben was detected at the lowest levels. The mean concentration of PBs followed the order methyl > propyl > ethyl > benzyl > butyl paraben across pregnancy trimesters. We found that ethyl paraben and triclosan were each positively and significantly associated with cortisol levels in postpartum women’s hair. Consistent with this, the mean cortisone concentration gradually increased from the first to the third pregnancy trimester, whereas cortisol reached the highest mean concentration at the second trimester. A significant positive association between cortisol and cortisone levels was observed. Further analyses revealed that mothers’ average TL was positively associated with ethylparaben and triclosan levels and inversely associated with benzylparaben levels. Last but not least, we found that cortisol/cortisone levels were positively associated with postpartum women’s TL in a statistically significant manner. Conclusions: In the present study, prenatal exposure to stress hormones and EDCs appears to exert a statistically significant impact on maternal TL dynamics. Full article

Leukocyte telomere length (LTL) is shortened in adults with type 1 diabetes (T1D), but less data is available concerning pediatric cases. Multiple factors affect LTL, namely genes, epigenetics, environmental factors, oxidation, and psychological stress. Children with T1D and their families experience chronic stress. This study aimed to investigate LTL in children with T1D (n = 35) aged 6–13 years old, in comparison to age-matched healthy counterparts (n = 35), and assess any correlation of LTL with perceived stress. Relative LTL (rLTL) was assessed through real-time qPCR. Morning serum cortisol, high-sensitivity C-Reactive Protein (hsCRP), and glycated hemoglobin (HbA1c) were measured. Children completed the validated questionnaires “Stress in Children” and “Pediatric Quality of Life”. Parents answered the “Perceived Stress Scale”. Children with T1D had a lower rLTL (p = 0.02) compared to age-matched healthy controls, higher hsCRP (p = 0.031), and a lower estimated quality of life (p = 0.01). RLTL was found to be lower in females with T1D (p < 0.001) and was positively related to the ‘gender–social support’ factor (p = 0.002) and diabetes duration (p = 0.045), adjusted for children’s age, parental age, and sociodemographic characteristics. These pilot findings indicate early emergence of shorter rLTL in T1D, pointing to a sexual dimorphism pattern. Insights into preventing LTL shortening in pediatric T1D can be gained from large-scale studies examining the impact of gender and social support. Full article

Positive mental health (PMH) has recently become a key topic in biomedical research. Previous studies have explored the correlation between biological and psychological measures, but only a few have focused on the relationship between PMH and aging. This study aimed: (i) to explore the association between PMH and biological aging; (ii) to determine if and to what extent the observed association could be explained by shared genetic and environmental effects. A total of 401 twins (age 19–81 years, 32% male) from the Italian Twin Registry were recruited, and the twin study design was applied. A self-report psychological test battery was used to evaluate several PMH components. Blood samples were collected from participants to determine telomere length (TL) and mitochondrial DNA copy number (mtDNAcn). TL was negatively associated with attachment anxiety (r = −0.11, p = 0.037). A bivariate twin model provided heritability estimates of 0.14 (95% CI 0.001–0.43) for TL and 0.32 (0.16–0.45) for attachment anxiety, and a substantial negative genetic correlation [r_g = −0.55 (−1.00–0.00)] between them. Under the limitations of a cross-sectional study with a self-report wellbeing assessment, these results suggest that anxiety in the relationship with a partner may contribute to accelerated TL shortening, and shared genetic factors may underlie this link. Full article

Telomerase reverse transcriptase subunit (TERT) is a key factor involved in telomere maintenance and genome stability, and the decline in its expression is closely related to cellular senescence. In this study, we established TERT monoallelic knockout (TERT+/−) and TERT overexpression (TERT-Over) cell lines in porcine iliac artery endothelial cells (PIEC) using CRISPR/Cas9 and PiggyBac systems to compare the effects of TERT monoallelic knockout versus overexpression on cellular biology. TERT expression and telomere length were assessed via qPCR and Western blot analysis. Cellular proliferation and senescence were evaluated using CCK-8 assays, cell cycle analysis, and SA-β-gal staining. Furthermore, the expression of key genes involved in cell proliferation, metabolism, and related signaling pathways was quantified using q-PCR. The results showed that the TERT mRNA level and telomere length decreased in TERT+/− cells. Meanwhile, we also observed that TERT+/− cells exhibited G1 phase arrest in the cell cycle, with suppressed proliferation and increased SA-β-gal-positive cells. This was accompanied by downregulation of cell cycle and proliferation-related genes, including c-Myc, the E2F family, and Ki-67, as well as downregulation of cell metabolism-related genes, including HIF1α, HK2, GLUT1, the SMAD family, FOXO1, and ATF4. In addition, cytochrome C was downregulated, suggesting activation of mitochondrial apoptotic signaling. Together, these findings indicate impaired proliferative and metabolic activity and are consistent with cellular senescence associated with telomere shortening. In TERT-overexpressing cells, the TERT gene expression and telomere length increase, cell proliferation accelerates, and the survival rate significantly increases under H₂O₂ treatment. This indicated that the overexpression of TERT can enhance resistance to oxidative stress, thus showing a kind of anti-aging phenotype. In conclusion, TERT monoallelic knockout induces cellular senescence-associated phenotypes in porcine endothelial cells, whereas TERT overexpression enhances proliferation and resistance to oxidative stress under the experimental conditions used in this study. The two porcine cell models established here may provide useful experimental materials for studying aging-related mechanisms and evaluating anti-aging interventions in large animals. Further studies are needed to directly determine their effects on cellular replicative lifespan. Full article

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, yet the association between folic acid (FA) intake and CRC risk remains controversial. This study investigated the effects of varying dietary FA levels on colorectal carcinogenesis and the underlying mechanisms. Methods: BALB/c mice were fed diets containing FA at <0.1, 2.0, 6.0, 8.0, or 20.0 mg/kg for 14 weeks. After 4 weeks, colorectal tumorigenesis was induced using the azoxymethane/dextran sulfate sodium (AOM/DSS) protocol. Tumor multiplicity, maximum tumor diameter, tumor volume, colorectal length, histopathology, and cell proliferation were assessed. Mechanistic assessments included uracil misincorporation, thymidylate synthase (TS), telomere attrition, genome-wide DNA methylation, RAP1 signaling, immune-related markers, and inflammatory cytokines in colorectal tissues. Results: Both FA deficiency (<0.1 mg/kg) and excess (8.0/20.0 mg/kg) increased colorectal tumor burden, with increased tumor number, larger maximum diameter, greater tumor volume, shortened colorectal length, and enhanced cell proliferation, whereas the 6.0 mg/kg diet group showed the lowest tumor burden. FA deficiency reduced TS expression, elevated deoxyuridine monophosphate (dUMP) levels, decreased deoxythymidine monophosphate (dTMP) levels, increased uracil misincorporation, and exacerbated telomere attrition, as evidenced by shortened telomeres and increased damage. In contrast, excessive FA intake induced Rap1 GTPase-activating protein (RAP1GAP) hypermethylation, reduced Rap1GAP expression, enhanced RAP1 activity, and upregulated programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) expression. Conclusions: Dietary FA can exhibit a U-shaped association with colorectal carcinogenesis, with protective effects observed within an optimal range. FA deficiency and excess may drive tumor development through distinct molecular pathways involving uracil misincorporation-induced telomere attrition and DNA methylation-mediated immunosuppression, respectively. Full article

Telomerase reverse transcriptase (TERT) plays a key role in tumorigenesis by maintaining telomere length, promoting chromosomal stability, and enabling cells to evade replicative senescence. TERT promoter mutations have been detected in various types of tumor; however, their prevalence in ameloblastoma has not been verified. This study aimed to determine the frequency of TERT promoter mutations in ameloblastoma. This retrospective study included formalin-fixed, paraffin-embedded (FFPE) tissue specimens and corresponding medical records from patients who underwent surgical treatment for jaw ameloblastoma at the Department of Oral and Maxillofacial Surgery, Kyungpook National University (Daegu, Republic of Korea) between January 2011 and December 2024. Clinical data were reviewed through January 2026. Of the 49 patients included, genomic DNA was extracted from two 5 μm thick FFPE tissue sections using the PANAMAX™ FFPE Plus DNA Extraction Kit (HLB PANAGENE, Daejeon, Republic of Korea), according to the manufacturer’s instructions. Hotspot TERT promoter mutations (C228T and C250T) were analyzed using the PNAClamp™ TERT Mutation Detection Kit (HLB PANAGENE, Daejeon, Republic of Korea). From a total of 73 TERT promoter mutation analyses performed in 49 patients, one of the recurrent cases harbored both C228T and C250T hotspot mutations. In the non-recurrent group, one case exhibited a C250T mutation. These findings indicate that TERT promoter mutations are rare in ameloblastoma. Full article

Chronic lymphocytic leukemia (CLL) exhibits marked clinical heterogeneity that is closely associated with genomic instability. Although cytogenetic abnormalities are widely used for risk stratification, they do not fully capture the biological complexity of the disease. Telomere dysfunction and alterations in DNA damage response pathways have been implicated in disease progression, but their relationship with cytogenetic risk in CLL remains incompletely characterized. In this study, peripheral blood mononuclear cells (PBMCs) from 48 CLL patients were analyzed. The analyzed PBMC fractions were enriched in leukemic B cells, with an estimated median tumor content above 85–90%. Cytogenetic profiles were obtained by conventional karyotyping following in vitro immunostimulation with DSP30 and interleukin-2 and classified according to ERIC and Döhner criteria. Telomere length was assessed by quantitative PCR, and CHEK1 and CHEK2 expression levels were quantified by RT–qPCR. Molecular parameters were compared across cytogenetic risk groups. Distinct molecular profiles were observed across cytogenetic categories. Favorable-risk CLL cases showed preserved telomere length, low CHEK1 expression, and maintained CHEK2 levels. Intermediate-risk cases, predominantly characterized by trisomy 12, exhibited moderate telomere shortening accompanied by increased CHEK1 expression and partial reduction of CHEK2. High-risk CLL cases, defined by del(11q), del(17p), or complex karyotypes, displayed pronounced telomere shortening, marked CHEK1 upregulation, and strong suppression of CHEK2. Telomere length was inversely correlated with cytogenetic risk (Spearman’s ρ = −0.68, p < 0.0001), and the CHEK1/CHEK2 expression ratio increased progressively with genomic complexity. These findings indicate that telomere length and CHEK1/CHEK2 expression patterns are closely associated with cytogenetic risk in CLL and may provide complementary biological information for risk stratification. Full article

Age estimation is an important component of forensic investigation, with applications in criminal casework, immigration assessments, and disaster victim identification. Determining whether an individual is a minor or an adult, or estimating the age at death of unidentified remains, can have significant legal and humanitarian implications. Traditional forensic age estimation methods rely primarily on anthropological and radiological assessment of skeletal development and degeneration; however, these approaches may be limited by subjectivity, population-specific reference standards, and reduced precision in adult age estimation. In recent years, molecular biomarkers have emerged as promising complementary tools for age prediction. Molecular approaches, including DNA methylation profiling, Y-chromosome-associated markers, RNA-based biomarkers, mitochondrial DNA alterations, proteomic signatures, and telomere length analysis, reflect biological processes associated with aging and may provide objective indicators that can be measured from biological samples. Among these methods, DNA methylation-based models currently demonstrate the strongest predictive performance and represent the most extensively studied molecular strategy for forensic age estimation. Nevertheless, several challenges remain before widespread forensic implementation can be achieved, including tissue specificity, environmental influences on biomarker stability, population variability, and the need for robust validation across laboratories and forensic sample types. This review summarises the current molecular approaches investigated for forensic age estimation, evaluates their biological basis and methodological limitations, and discusses their potential integration into forensic workflows. While molecular techniques offer promising avenues for improving age estimation, further standardisation, validation, and careful interpretation are required before they can be routinely applied in forensic practice. Full article

The rapid expansion of cardiac imaging has substantially increased patient and occupational exposure to low-dose ionizing radiation. Evidence suggests that cumulative exposures below 100 mSv may contribute to long-term risks of cancer and non-cancer diseases, including cardiovascular disease. However, establishing causality at these dose levels is challenging, as epidemiological studies are limited by heterogeneous endpoints, uncertainties in dose reconstruction, and incomplete control of confounding factors. Molecular biomarkers offer a promising strategy to bridge the gap between radiation exposure and clinically manifest disease, enabling more precise individualized risk assessment and targeted preventive strategies. This review summarizes current evidence on genetic and epigenetic biomarkers for evaluating the biological effects of radiation in cardiac imaging and interventional cardiology and examines their potential role in risk stratification and occupational surveillance. Genetic markers—including γ-H2AX foci, micronucleus assays, and telomere length alterations—alongside epigenetic modifications such as DNA methylation changes and microRNA expression profiles provide sensitive indicators of radiation-induced cellular damage. Integrating biomarker profiling with individualized dosimetry and longitudinal follow-up may improve risk prediction, enhance occupational protection, and support safer, more sustainable imaging practices in contemporary cardiovascular care. Full article

Maternal stress during lifetime and pregnancy may influence offspring epigenetic age, impacting long-term health. We conducted a systematic review and meta-analysis of associations between maternal stress and epigenetic aging markers: telomere length (TL) and DNA methylation (DNAm) age acceleration. The systematic search was performed according to PRISMA guidelines and registered on PROSPERO (ref. CRD42023474640). Fixed and random effect meta-analyses were carried out, stratified by stress type and marker type (TL, DNAm). Sixteen studies met inclusion criteria; 12 were meta-analyzed (10 TL, 2 DNAm). Due to high heterogeneity, restricted maximum likelihood meta-analysis suggested significant inverse associations between maternal stress and offspring TL. Perceived stress was associated with shorter TL (p-value = 7 × 10⁻⁴, β = −0.085, 95%CI [−0.135, −0.036]), as was lifetime stress/trauma (p-value = 0.01, β = −0.209, 95%CI [−0.370, −0.049]). In contrast, maternal stress showed no significant associations with DNAm age acceleration (p-value = 0.32). Both perceived maternal stress and maternal stress were associated with shorter offspring TL, suggesting that stress exposure across the maternal lifespan influences offspring biological aging markers. No significant association was observed with DNAm-based aging clocks. Further studies with larger sample sizes and more homogeneous settings are needed to confirm and expand upon our observations. Full article

The spotted seal (Phoca largha) is an ice-associated pinniped in the Northwest Pacific and is a subject of conservation concern under increasing environmental and anthropogenic pressures; however, genomic studies have been constrained by the absence of a high-quality reference genome. Here, we present a near-telomere-to-telomere (near-T2T), gap-free genome assembly of P. largha spanning 2.39 Gb and comprising 16 chromosome-length sequences, with a scaffold N50 of 184.39 Mb and high completeness (99.34% complete BUSCOs). Compared with the previous chromosome-level assembly, the new genome improves contiguity and gene-space completeness. Comparative analyses across 20 carnivoran species resolve P. largha as sister to Phoca vitulina with an estimated divergence time of ~2.1 Ma. Branch-site positive-selection analyses and gene-family evolution analyses identify lineage-associated changes, and enrichment results motivate focused investigation of integument-related gene families. Targeted analyses of keratin (KRT) and matrix metalloproteinase (MMP) families reveal contrasting chromosomal organisation and evolutionary dynamics: KRTs form large chromosomal clusters with broadly conserved synteny across Carnivora but lineage-dependent remodelling within clusters, whereas MMPs are dispersed and display largely conserved orthologous correspondence. This high-quality genome provides a high-quality resource for pinniped comparative genomics and for elucidating the genomic architecture of skin and fur adaptation. Full article

Background: Inflammatory and metabolic risk factors are associated with adverse health outcomes among aging women. Physical activity may reduce these detrimental changes, helping to promote healthier aging. Methods: Seventy-nine non-obese women, aged 20–50 years, completed a supervised 4–8 week aerobic training program with measurements obtained before and after the intervention. The 20–30-year group (n = 29) completed a 4-week training program, with 13 participants fasting during training, while the 30–50-year group (n = 50) completed an 8-week program. Fasting blood sugar (FBS), lipid profile, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA IR), body composition, multiple cytokines, oxidative stress markers and leukocyte telomere length were assessed. Mixed-effects linear models were used to test age-by-activity (before versus after) interactions, adjusting for body mass index (BMI), fasting status and training duration. Results: Physical activity was associated with a higher superoxide dismutase (SOD) activity, lower tumor necrosis factor alpha (TNF α) concentrations, increased weekly Metabolic Equivalent of Task (METs) and a modest reduction in high-density lipoprotein (HDL) cholesterol. Significant age-by-activity interactions were identified for fat-free mass, total cholesterol, HDL cholesterol, FBS and TNF α, exhibiting attenuated or reversed age-related slopes for these traits after training. Specifically, older active women exhibited less age-related increases in FBS and TNF α and greater age-related reductions in total cholesterol, whereas the preservation of fat-free mass was more pronounced among younger participants. Conclusions: A short moderate-intensity aerobic program was sufficient to improve antioxidant defenses and inflammatory status and reshape age-group-specific responses to the training of selected glycemic, lipid, inflammatory and functional markers in healthy women, partly mitigating adverse age-associated changes, particularly in older participants. By modeling age-by-activity interactions across various metabolic and inflammatory risk factors, this study provides evidence that short-term moderate aerobic training can reshape age-group-specific cardiometabolic responses to training. Full article

Traditional Chinese medicine plays an important role in human health, but due to the complexity of its active fraction, its therapeutic mechanism still needs further clarification. Polygalae Radix is one of the traditional Chinese medicines, which was recorded in Shennong Classic of Materia Medica with the effect of prolonging life. In the present study, we isolated a small molecule compound with anti-aging effects, 3,6′-disinapoyl sucrose (DISS), from Polygalae Radix under the guidance of the replicative lifespan assay of K6001 yeast strain. It extended the lifespan of yeast and alleviated etoposide-induced aging in 3T3 cells. Furthermore, this compound increased the telomerase activity and the length of telomeres, and targeted the SIRT1 signaling pathway, respectively. In addition, it improved the survival ability of yeast under oxidative stress conditions, decreased ROS and MDA levels, and increased the activity of SOD, CAT and GPx enzymes. Moreover, DISS enhanced autophagic flux, as demonstrated by assay of the YOM38-GFP-ATG8 yeast strain. In conclusion, DISS from Polygalae Radix exerts anti-aging effects by protecting telomeres, regulating the SIRT1/p53/p21 signaling pathway, mitigating oxidative stress and modulating autophagy. Thus, this study provides scientific evidence for the use of Polygalae Radix as an anti-aging herb. Full article

Rapid pain progression in knee osteoarthritis (OA) is heterogeneous and may reflect redox-related mechanisms. We performed an exploratory analysis in Osteoarthritis Initiative (OAI) participants, combining nuclear genome-wide association, mitochondrial DNA (mtDNA) haplogroups, and leukocyte telomere length. Rapid pain progression was defined using the rescaled Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain (0–100) within 24-month windows. An additive genome-wide association study (GWAS) in 2946 participants tested 7,762,204 imputed variants, adjusting for age, sex, body mass index (BMI) and three principal components. Haplogroups were analysed in 3357 participants, and telomere length (telomere-to-single-copy gene, T/S, ratio) was analysed in 301 participants. No variant reached genome-wide significance (p < 5 × 10⁻⁸), but six loci were suggestive (p < 5 × 10⁻⁶), with minimal inflation (λ = 0.995). mtDNA haplogroup H was nominally associated with rapid pain progression (odds ratio, OR = 1.179, p = 0.023). Rapid pain progressors had shorter baseline telomeres (0.825 ± 0.268 vs. 0.985 ± 0.375; p < 0.001), and telomere length was inversely associated with progression (OR per 1-unit T/S = 0.260, p = 0.007). These preliminary, hypothesis-generating findings are compatible with a redox-related interpretation of rapid pain progression and require external validation in independent cohorts, while providing candidates for future mechanistic studies. Full article