Search Results (398)

Porcine somatic cell nuclear transfer (SCNT) demonstrates significant potential for application in biomedical research, agricultural breeding, and xenotransplantation. However, compared to in vivo fertilized embryos, SCNT embryos exhibit suboptimal developmental capacity, higher rates of abortion, and neonatal abnormalities, which collectively hinder the large-scale application of this technology. Such developmental anomalies arise from a complex interplay of interconnected factors, primarily incomplete epigenetic reprogramming (the core driver), telomere shortening, mitochondrial dysfunction, and technical manipulation-related damage—all of which disrupt the spatiotemporal regulation of gene expression and embryonic lineage commitment. This article provides a critical and integrated review of porcine SCNT research, establishing a coherent conceptual framework that links biological mechanisms, developmental defects, diagnostic tools, and improvement strategies. We emphasize mechanistic insights into key barriers, evaluate the efficacy and limitations of existing diagnostic and therapeutic approaches, and highlight pig-specific biological features that distinguish porcine SCNT from other mammalian models. This review aims to offer a novel perspective on unresolved questions in the field and provide a rigorous reference for in-depth studies on porcine SCNT embryo development. Full article

Background/Objectives: Mitochondrial DNA (mtDNA) variations are linked to psychiatric disorders, but their association with internet gaming addiction (IGA) remains unexplored. We investigated mitochondrial D-loop D310 and D514 regions and mtDNA copy number (mtCN) in male adolescents with and without IGA, exploring their associations with leukocyte telomere length (LTL). Methods: Questionnaires assessed IGA in 206 male adolescents. Blood samples were analyzed for (C)_n repeats at D310 and (CA)_n repeats at D514. Relative mtCN and LTL were measured using quantitative PCR. Results: D310 polymorphism distribution differed significantly between the IGA and non-IGA groups (p = 0.040). Among the (C)_n repeats, (C)₈ frequency at D310 was significantly lower in the IGA group than in the non-IGA group (p = 0.017). Multivariable logistic regression initially identified the (C)₈ polymorphism as an independent predictor reducing IGA likelihood (OR = 0.474, p = 0.014), although this nominal association did not remain statistically significant after formal Bonferroni correction. mtCN differences were not significant (p = 0.247). Notably, LTL was significantly shorter in the IGA group among carriers of (C)₈ and (CA)₅ polymorphisms (both p = 0.001). Multivariable linear regression confirmed that IGA remained robustly associated with shorter LTL (B = −40.180, p < 0.001), while (C)₈ and (CA)₅ repeats were not independently associated with LTL shortening. Conclusions: While the (C)₈ polymorphism’s direct genetic contribution to IGA susceptibility remains preliminary and hypothesis-generating due to multiple testing attenuation, IGA exhibits a robust, independent association with LTL shortening. Mitochondrial genomic backgrounds may play a subtle, modulatory role in behavioral addiction pathways, warranting further longitudinal validation. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent condition in both adults and children. Dysregulated telomere maintenance has been proposed as a mechanism underlying disease progression, although pediatric evidence remains limited and controversial. This study aimed to investigate the relationship between telomere length (TL) and hepato-metabolic features in children with MASLD. A total of 212 pediatric patients with biopsy-proven MASLD and 40 controls were enrolled. Telomere length in leukocytes (LTL) and liver tissue (HTL) was measured using quantitative polymerase chain reaction, and telomerase reverse transcriptase (TERT) mRNA and protein expression were also evaluated. Associations between TL and clinical, metabolic, and perinatal variables were analyzed. Children with MASLD showed significantly shorter LTL and HTL compared to controls. Shorter LTL was observed in more advanced steatohepatitis (MASH) and was associated with fibrosis severity. TERT expression was reduced in patients. LTL was also associated with perinatal factors, including preterm birth and low birthweight. Multivariable analysis identified MASH, fibrosis, and small-for-gestational-age status as independently associated with shorter LTL. In conclusion, LTL is associated with disease severity in pediatric MASLD, particularly fibrosis. These findings support a potential role of telomere dynamics in disease progression, although causal relationships require confirmation in longitudinal studies. Full article

Spinocerebellar ataxia type 7 (SCA7) is a hereditary disorder characterized by degeneration of the cerebellum and retina. SCA7 is caused by the expansion of a polyQ tract in the ATXN7 gene, leading to protein misfolding, transcriptional dysregulation, and neuronal/glial degeneration. Recently, altered DNA damage response (DDR) was revealed in SCA7, which may contribute to disease pathogenesis. Impaired DDR causes DNA damage, which in turn triggers cellular senescence. Consistently, senescent cells were identified in the cerebellum Purkinje layer of an SCA7 mouse model. In this study a Müller glial model (MIO-M1) expressing normal (10Q) or expanded (64Q) ataxin-7 was utilized to ascertain whether mutant protein induces genomic instability and consequently the emergence of senescence. PolyQ ataxin-7 elicits nuclear lamina disorganization, γH2AX foci (DDR marker), micronuclei and telomere shortening, which indicate genomic instability. Furthermore, 64Q cells expressing polyQ ataxin-7 exhibited senescence hallmarks, including heterochromatin loss and increased senescence-associated β-galactosidase activity, but not p21 nor p53 expression. Instead of the senescence-associated enlargement of nucleoli, these cells exhibited nucleolar disaggregation. Together, these findings indicate that the expression of polyQ ataxin-7 disrupts the nuclear architecture, thereby inducing genomic instability. This, in turn, results in a senescence-like phenotype, a phenomenon that may contribute to glial pathogenesis. Full article

Brucellosis and tuberculosis (TB) are chronic infectious diseases of international public health importance, with developing countries being most affected. The diagnosis of brucellosis and tuberculosis co-infection remains challenging because both diseases present with overlapping nonspecific clinical manifestations, such as prolonged fever, fatigue, and weight loss, and elicit similar cell-mediated immune and inflammatory responses, which can complicate differential diagnosis, particularly in endemic regions. Recently, it has been shown that chronic infections affect cell stress pathways such as oxidative stress and telomere function. The current literature review provides an overview of the relationship between brucellosis and TB at a molecular level, focusing on telomere biology, oxidative stress and the mechanisms of antimicrobial resistance. Due to chronic immune response in brucellosis and TB patients, an increase in reactive oxygen species (ROS) levels is observed, leading to DNA damage and subsequent telomere shortening and alteration of telomerase activity. These alterations might be responsible for immune senescence, weakened defense response and persistent infection. In addition, different methods of drug resistance have been discovered among brucellae and mycobacteria, such as mutation in target sites, efflux systems and intracellular persistence, making their eradication difficult. Finally, the potential role of telomere-related genes and biomarkers of oxidative stress in diagnosis and prognosis is also highlighted. Insights into these interrelated pathways would allow us to have a better understanding of host–pathogen interactions and hence offer a possible means of developing new strategies in the fight against co-infection by finding new biomarkers. Full article

Background/Objectives: Telomeres are critical biomarkers of biological aging, with shortened leukocyte telomere length strongly linked to all-cause mortality and age-related disease risk. Although exercise modulates telomere dynamics, the field’s evolution from descriptive measurements to mechanistic inquiries involving redox biology and epigenetics remains incompletely mapped. This study systematically characterized the global research landscape of telomere–exercise science over 25 years to establish a strategic evidence base for precision exercise prescription. Methods: A bibliometric analysis was conducted on 858 publications from the Web of Science Core Collection (2000–2025). CiteSpace and VOSviewer were used for keyword co-occurrence analysis, strategic thematic mapping, and citation burst detection to visualize global research trends and identify emerging frontiers. Results: Annual publication volume grew from 2 (2000) to 71 (2025), with a compound annual growth rate of 15.4%. China emerged as one of the leading global contributors. Thematic analysis revealed a paradigm shift from descriptive leukocyte telomere length studies toward mechanistic investigations of oxidative stress, mitochondrial homeostasis, and epigenetic clocks. Keyword network analysis confirmed oxidative stress and inflammation as central hubs, mediating telomere protection via redox regulation and non-canonical telomerase functions. Conclusions: Exercise preserves telomere integrity primarily through redox–mitochondrial homeostasis, hormesis-driven antioxidant upregulation, and non-canonical telomerase activation. For aging populations and individuals at metabolic risk, aerobic training and high-intensity interval training (HIIT) are recommended as first-line non-pharmacological interventions for healthspan extension. Leukocyte telomere length and telomerase activity should be integrated as biomarkers in preventive medicine practice. Future large-scale randomized controlled trials incorporating multi-omics approaches and sex-stratified analyses are warranted to establish individualized dose–response guidelines for precision exercise prescription. Full article

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally among older adults. Similar to humans, age-related declines in cardiac function are observed in C57BL/6 mice. Angiotensin-converting enzyme 2 (ACE2), a key component of the renin–angiotensin system (RAS), counteracts detrimental RAS effects by converting angiotensin II (Ang II) to angiotensin-(1-7) (Ang-(1-7)), thereby playing a critical role in mitigating CVD pathogenesis. Here, we utilized transgenic K18-hACE2 mice to investigate the protective effects of ACE2 against cardiac aging. Histological and morphometric analyses revealed significant reductions in heart weight and improvements in cardiac structure in K18-hACE2 mice compared to wild-type controls. Furthermore, aged C57BL/6 mice exhibited progressive cardiac aging phenotypes, including mitochondrial dysfunction, telomere shortening, and immune dysregulation—all of which were significantly attenuated in K18-hACE2 mice. These findings demonstrate the protective role of ACE2 in cardiac aging and highlight its potential as a therapeutic target for anti-aging interventions. Full article

Environmental pollution has emerged as one of the most significant threats to human and ecosystem health, with growing evidence suggesting that chronic exposure to toxic substances may accelerate aging. The concept of gerontogens, toxic compounds capable of accelerating this biological process, has gained increasing attention in toxicological research, particularly in the context of global demographic shifts toward older populations. Current research on gerontogens relies heavily on invertebrate models with short lifespans, such as Caenorhabditis elegans, Drosophila melanogaster, and Saccharomyces cerevisiae, which are valuable for studying conserved mechanisms in aging pathways, but present significant limitations for translational accuracy to many aspects of vertebrate biology. Vertebrate models traditionally employed in toxicology, including mice and zebrafish, require substantially longer experimental timelines and higher financial investments, making lifetime exposure and aging assays particularly challenging. In this context, the turquoise killifish Nothobranchius furzeri emerges as a highly promising vertebrate model for aging toxicology research. Recognized as the shortest-lived vertebrate species maintained under laboratory conditions, N. furzeri reaches sexual maturity within 14 days and displays complete senescence by 4 months of age, at which point individuals are considered elderly, offering a decisive advantage over conventional vertebrate models. Furthermore, its capacity for embryonic diapause enables practical embryo storage, long-distance transport, and synchronized hatching, greatly facilitating experimental designs. Although N. furzeri is well established in gerontological research, with studies addressing hallmarks of aging such as telomere shortening, neurodegeneration, and cellular senescence, its application in ecotoxicology remains remarkably limited, with fewer than 10 published studies to date. This article argues that N. furzeri may represent a critical bridge between toxicology and aging research, offering an efficient and translationally relevant platform for investigating the effects of environmental contaminants on vertebrate aging. Current limitations of the model, such as lack of husbandry standardization, are also discussed. Expanding its use in this field holds considerable potential for advancing evidence-based strategies in public health and environmental conservation related to chronic exposure to contaminants. Full article

Telomere length (TL) is a key determinant of cellular aging and genomic stability, influenced by genetic, molecular, and environmental factors. Progressive telomere shortening has been associated with degenerative and cardiovascular diseases, whereas longer telomeres have been linked to an increased risk of cancer, highlighting a dual and context-dependent relationship between TL and disease susceptibility. Evidence from genome-wide association studies (GWAS) and Mendelian randomization analyses indicates that TL is a highly heritable and polygenic trait, regulated by variants in genes such as TERT, TERC, RTEL1, and POT1, as well as components of the shelterin and CST complexes. This study integrates genetic variants associated with telomere shortening and elongation, including their functional classification, proposed molecular mechanisms, and ACMG/AMP categorization, together with global and Latin American allele frequency data. These variants may participate in key processes such as telomerase activity, telomerase RNA stability, and telomere replication, thereby influencing susceptibility to multiple diseases. However, current evidence is largely derived from European and Asian populations. Given the highly admixed nature of Latin American populations, population-specific studies are required to identify unique genetic determinants and to improve the application of precision medicine. Full article

Aging is the primary biological driver of progressive cellular dysfunction and a major risk factor for disease development. The lungs and kidneys are highly vulnerable to cellular damage during aging due to their continuous exposure to environmental and metabolic stressors. Increasing evidence supports the existence of a bidirectional communication axis between the lungs and kidneys. In this review, we propose an integrative mechanistic framework that links alterations in cell turnover along this axis during aging. Based on the literature reviewed, we found that age-related cellular changes induce cellular senescence. Senescent cells undergo irreversible cell cycle arrest; furthermore, telomere shortening limits cell proliferation and promotes resistance to apoptosis. However, apoptosis can increase when a critical damage threshold is reached. In this context, senescent cells acquire a senescence-associated secretory phenotype (SASP) and release circulating mediators that can transmit damage signals between the lungs and kidneys. Taken together, these processes promote a pathological feedback loop in which age-related changes in one organ can exacerbate dysfunction in another, reinforcing a bidirectional axis of damage that increases susceptibility to developing lung and kidney diseases. Full article

Aging is a multifactorial biological process characterized by a progressive decline in functional capacity at the molecular, cellular, tissue, and organismal levels. The aim of this review is to summarize current concepts of aging mechanisms and the prevention of age-related pathologies from a lymphological perspective, taking into account contemporary literature data and the results of our own studies. Currently, two major concepts dominate in gerontology: programmed aging, which considers aging as a genetically determined process, and damage accumulation theories, which associate aging with the progressive accumulation of molecular and cellular damage. The hallmarks of aging include genomic instability, telomere shortening, epigenetic alterations, impaired proteostasis and macroautophagy, dysregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, dysbiosis, hormonal imbalance, and disturbances in interstitial humoral transport and lymphatic outflow. At the tissue and organ levels, impairment of lymphatic drainage is of particular importance, leading to interstitial fluid stagnation and the accumulation of toxic metabolites, which exacerbate cellular and subcellular dysfunction. Phytotherapeutic agents containing flavonoids, phenolic compounds, terpenoids, glycosides, polysaccharides, and other biologically active substances exhibit antioxidant, anti-inflammatory, and cytoprotective properties. They inhibit lipid peroxidation, reduce excessive nitric oxide production, and contribute to the restoration of interstitial humoral transport and lymphatic outflow. Interstitial humoral transport and the lymphatic system, together with renal mechanisms, play key roles in maintaining body fluid homeostasis. Targeted regulation of lymphatic system function may help reduce tissue congestion, maintain physiological homeostasis, and improve quality of life in the elderly. 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