Search Results (605)

Vitamin D₃ plays a pivotal role not only in bone health but also in the functioning of the nervous system, particularly in the context of age-related neurodegenerative diseases such as Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease. Vitamin D₃ deficiency has been associated with cognitive decline, heightened inflammation, and shortened leukocyte telomere length, which may contribute to accelerated cellular aging. Therapeutic interventions involving vitamin D₃ have been reported in selected clinical studies and meta-analyses to potentially enhance cognitive function, decrease amyloid β biomarkers, and prolong telomere length, although heterogeneity remains across study designs and populations. Furthermore, vitamin D₃ has been shown to influence the expression of genes implicated in DNA repair and oxidative stress response, including NRF2, OGG1, MYH, and MTH1. This narrative review synthesizes current knowledge on the molecular mechanisms of vitamin D₃ action in the context of neuroprotection and discusses potential directions for future research, including its possible therapeutic applications in neurodegenerative diseases. Full article

Background: Although telomere length maintenance is a common characteristic of hematological malignancies, the role of telomere length as a prognostic factor to stratify acute lymphoblastic leukemia (ALL) patients depending on their risk of relapse remains elusive. Methods: This knowledge gap motivated us to examine telomere length values in children with ALL at the time of diagnosis and after treatment using quantitative polymerase chain reaction (qPCR) (n = 35). To achieve high-resolution precision and cell specificity, a quantitative fluorescence in situ hybridization (qFISH) technique was developed (n = 5). Results: The results demonstrated statistically significant evidence of telomere shortening in the lymphoblasts of children with ALL but not in the lymphocytes of children after remission following treatment. Our findings also suggested a significant association between telomere shortening and a high risk of relapse disease. Last but not least, our preliminary results showed a trend that telomere shortening was more pronounced in children with B-ALL compared to those with T-ALL in a non-significant manner. Conclusions: Consequently, the current study provides preliminary insights into the potentially substantial prognostic value of telomere length in the progression of pediatric ALL, with the possibility of predicting treatment response. To clarify the application of telomere length as a possible biomarker for disease progression and treatment response in children with ALL, the telomere length values of additional participants need to be examined in further studies. Full article

Background and Objectives: Maternal telomere length (TL) has been proposed as a potential biomarker of biological aging and pregnancy outcomes, yet evidence in Central and Eastern European populations remains scarce. This study aimed to investigate the association between maternal TL and neonatal parameters in a clinically healthy cohort. Materials and Methods: We conducted a prospective observational study including 134 mother–infant pairs at the “Pius Brînzeu” Emergency County Clinical Hospital, Timișoara. All deliveries were performed by cesarean section for maternal indications unrelated to fetal condition. Maternal blood samples were collected at admission, and relative TL was measured by quantitative PCR. Neonatal outcomes included birth weight, length, head circumference, gestational age, and Apgar scores. Results: Longer maternal TL was positively correlated with birth weight (r = 0.515, p < 0.001), length (r = 0.559, p < 0.001), head circumference (r = 0.468, p < 0.001), gestational age (r = 0.444, p < 0.001), and Apgar scores at 1 (r = 0.714, p < 0.001) and 5 min (r = 0.684, p < 0.001). Logistic regression showed that shorter maternal TL independently predicted suboptimal 1 min Apgar (<8), with an adjusted odds ratio of 0.68 (95% CI: 0.51–0.91). Conclusions: Maternal TL is strongly associated with neonatal growth and vitality measures, supporting its potential as a simple, non-invasive biomarker for perinatal risk assessment. Full article

Cadmium exposure has been associated with shortened telomeres, alterations in DNA methylation patterns, and increased mortality. However, the role of DNA methylation in mediating the relationship between cadmium and telomere dynamics is still unclear. Additionally, it is unknow how telomere dynamics and DNA methylation alterations may affect the association between cadmium exposure and mortality outcomes. We utilized data from 8716 National Health and Nutrition Examination Survey (NHANES) participants aged 18 and above, collected between 1999 and 2002, and linked these to mortality outcomes from the National Center for Health Statistics (NCHS) through 2019. In the final model, ln-blood cadmium was significantly and inversely associated with ln-T/S ratio (β = −0.043, 95% CI: −0.059 to −0.027, p < 0.001), while ln-Horvath DNAmTL was strongly and positively associated with ln-T/S ratio (β = 1.782, 95% CI: 1.467 to 2.097, p < 0.001). Moreover, ln-blood cadmium also showed a significant inverse association with ln-Horvath DNAmTL (β = −0.010, 95% CI: −0.014 to −0.006, p < 0.001). Structural equation modeling showed that the association between cadmium and T/S ratio was mediated by Horvath DNAmTL, with a total effect of −0.044, a direct effect of −0.027, and an indirect effect of −0.017. Furthermore, stratified analyses revealed that a 1-unit increase in ln-blood cadmium was associated with higher all-cause mortality, with hazard ratios (HR) of 1.47 for participants with T/S ratio below the median and 1.41 for those above. Similar patterns were observed for cardiovascular (HR = 1.68 vs. 1.30) and cancer mortality (HR = 1.75 vs. 1.42). For Horvath DNAmTL, the association was significant only for all-cause mortality (HR = 1.36 vs. 1.31). However, no significant interactions were detected. In conclusion, our findings suggest that Horvath DNAmTL is associated with the relationship between cadmium and telomere length, suggesting a potential DNA methylation pathway that warrants further longitudinal investigation. Individuals with lower T/S ratios or Horvath DNAmTL appear to be more susceptible to cadmium-related mortality. Further research is necessary to confirm these results. Full article

In this work, we provide an overview of the age determination methods of amphibians and reptiles, critically evaluating their methodological principles, utility (including range of applicability), as well as experimental and biological limitations. Potentially, the most reliable age estimation method is the capture–mark–recapture (CMR) technique, allowing a precise chronological age estimation of wild individuals. However, this is a time-consuming method and is not always applicable. Among the indirect methods of age estimation, skeletochronology is one of the most reliable techniques and has been successfully applied in numerous species of amphibians and reptiles. Skeletochronology is based on the interpretation of the growth marks (especially lines of arrested growth or LAGs) that form in hard-mineralized tissues. Other indirect methods such as the counting of growth marks on epidermal scutes, dermal scales, and claw sections have shown to be less reliable and/or have a more limited range of applicability. Recently, the estimation of chronological age using molecular methods has acquired new perspectives from different approaches. Among them, measurements of telomere length and DNA methylation represent promising and minimally invasive methods, but their effective use requires further refinement and testing on a larger number of species. Full article

Background: Emerging evidence suggests that polyphenols may contribute to the attenuation of telomere attrition and the upregulation of insulin-like growth factor 1 (IGF-1), primarily in animal and cell studies, and to a lesser extent in humans. Pomegranate extract, known for its high antioxidant capacity, has shown promise in preventing telomere shortening and enhancing IGF-1 levels, but evidence in humans is lacking. Objective: To investigate the effects of pomegranate extract on telomere length and serum IGF-1 levels in older adults aged 55–70 years. Methods: Participants took part in a two-arm double-blind parallel trial, receiving either placebo capsules (maltodextrin) or pomegranate extract (740 mg) daily for 12 weeks. At baseline, week 6 and week 12, anthropometric measurements, blood pressure readings and blood samples were collected. Telomere length and serum IGF-1 levels were assessed. Results: A total of 72 participants completed the study. Analysis showed a significant effect of treatment and time on IGF-1 ((F_2,136 = 3.43, p = 0.04), with levels significantly increasing in the pomegranate extract group at week 12. No significant effects on telomere length were noted. Weight status, physical activity, age, gender and energy intake did not impact the outcomes. Conclusions: Pomegranate extract significantly increased IGF-1 levels and could exert a positive role on vascular ageing. Further research is needed to replicate these findings and confirm its long-term benefits. Extended studies are required to elucidate its potential to counteract telomere shortening. Full article

Children are more vulnerable to the adverse effects of pesticides due to physiological factors and behavioral habits. This study aimed to evaluate the impact of pesticide exposure on telomere length (TL) and the enzymatic activity of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and β-glucuronidase (β-Glu) in children ages 6 to 12 from an agricultural area in Mexico. A cross-sectional, descriptive, and analytical study was conducted involving 471 children. Blood samples were collected to assess TL through qPCR and enzymatic activity using established protocols. A pesticide exposure index (PEI) was developed incorporating biomarker levels, urinary dialkylphosphates (DAP), and proximity to farmland. No significant differences were observed in AChE activity across communities; however, BuChE activity was significantly higher in agricultural communities, while β-Glu activity varied among communities. Notably, children aged 6 in agricultural areas showed TL values similar to 12-year-old children in the reference community. Adjusted regression models revealed significantly shorter TL in children from agricultural communities and in children with moderate to high PEI. The findings indicate that chronic pesticide exposure was associated with telomere shortening in children, suggesting accelerated biological aging and potential genomic instability during critical developmental periods. Full article

Mushrooms, renowned for their nutritional value and bioactive compounds, offer potential health benefits, including antioxidants and anti-aging properties. Aging, characterized by cellular and tissue decline, is often associated with autophagy dysfunction, a crucial cellular cleaning process. This study aimed to investigate the neuroprotective, hepatoprotective, and antimicrobial properties of extracts from four medicinal and edible mushrooms: Ganoderma lucidum, Hericium erinaceus, Pleurotus ostreatus, and Agaricus bisporus. The protein, total phenol, and flavonoid content of mushroom extracts were determined. Aging was induced with 120 mg/kg D-galactose and treated with 500 mg/kg mushroom extracts. The study evaluated liver enzyme levels, histopathological changes in liver and brain tissues, gene expression correlated to neurodegeneration (SEPT5-SV2B-ATXN2-PARK2), telomere length, and immunomodulatory and pro-inflammatory (IL-2-IL-4-IL-6) gene expression pathways. Additionally, the antimicrobial potential of mushroom extracts was assessed against several bacteria (Lysinibacillus odyssey, Lysinibacillus fusiformis, Klebsiella oxytoca, and Escherichia coli) using agar well diffusion and lowest minimum inhibitory concentration (MIC) methods. By exploring these diverse aspects, this study aimed to provide a foundation for a better understanding of the potential of mushrooms as natural neuroprotective, hepatoprotective, and antimicrobial agents and their potential applications in human health. Results indicated that all mushroom extracts effectively mitigated oxidative stress. Agaricus bisporus exhibited the highest protein and flavonoid content, and Pleurotus ostreatus displayed the highest phenolic content. Notably, Hericium erinaceus and Ganoderma lucidum extracts demonstrated significant neuroprotective and hepatoprotective properties against D-galactose-induced aging, as evidenced by histopathological examination. All extracts exhibited a significant decrease (p < 0.001) in liver function (serum levels of aspartate aminotransferase (GOT) and alanine aminotransferase (GPT)) and showed immunomodulatory and anti-inflammatory effects, characterized by upregulated IL-2 and IL-4 gene expression and downregulated IL-6 gene expression. Hericium erinaceus demonstrated the most pronounced upregulation (p < 0.001) of SEPT5, SV2B, and telomere length gene expression, suggesting potential anti-aging effects. Furthermore, all mushroom extracts displayed antimicrobial activity against the tested bacterial strains, except Hericium erinaceus, which exhibited antibacterial activity solely against E. coli. Agaricus bisporus exhibited the largest inhibition zones (22 ± 0.06 mm) against Lysinibacillus odyssey, while Hericium erinaceus displayed the largest inhibition zone against E. coli. The MIC value was observed with Agaricus bisporus extract against Lysinibacillus odyssey (1.95 ± 0.16 mg/mL). Lysinibacillus fusiformis exhibited the highest resistance to the tested mushroom extracts. These findings suggest that these edible and medicinal mushrooms possess a wide range of health-promoting properties, including neuroprotective, hepatoprotective, and antimicrobial activities. Further research is needed to fully understand the underlying mechanisms and optimize applications. However, our results provide a strong foundation for exploring these mushrooms as potential natural agents that promote overall health and combat age-related decline. Full article

Research on the post-deployment reintegration needs of women veterans is limited. Non-traditional support may enhance mental health. Relationships with animals and volunteering may aid those with post-traumatic stress disorder (PTSD). Using the biopsychosocial model, we examined whether participation in an 8-week service dog training program (SDTP) affected telomere length (TL), heart rate variability (HRV), PTSD symptom severity, perceived stress, and anxiety in female veterans with PTSD, as well as whether combat exposure influenced these relationships. Female veterans (ages 32–72, M = 45.9, SD = 11.8) with PTSD were randomized to either the SDTP group (n = 13) or a comparison group (n = 15) that received dog training video content. The interventions lasted one hour weekly for 8 weeks. Outcomes were assessed pre-, mid-, and post-intervention. Linear mixed models with random intercepts examined changes from pre- to post-intervention and compared changes by group and combat exposure. TL changes differed [F(1,11.65) = 3.543, p = 0.085] by intervention. In the SDTP group, TL increased, indicating reduced cellular senescence (i.e., slower biological aging), whereas TL decreased in the CI group. Combat exposure moderated these changes [F(1,12.36) = 5.41, p = 0.038]. HRV changed by intervention group [F(1,389.08) = 10.623, p = 0.001]. HRV decreased (stress increased) in the SDTP group but not in the CI group. Combat exposure did not moderate HRV changes. PTSD symptom severity [F(1,48.04) = 19.22, p < 0.001], perceived stress [F(1,48.48) = 14.65, p < 0.001], and anxiety [F(1,47.30) = 6.624, p = 0.013] decreased significantly from pre- to post-interventions; the decreases did not differ by intervention or combat exposure. Full article

Background/Objectives: Fetal telomere length (FTL) at birth is considered a key marker of early biological aging and future disease risk. While chronic inflammation is known to accelerate telomere attrition in adults, limited evidence exists on how maternal inflammation during pregnancy impacts FTL. This study aimed to investigate the association between maternal systemic inflammatory status in late pregnancy and FTL at birth. Methods: We conducted a prospective cohort study including 150 clinically healthy pregnant women recruited in the third trimester. Participants were stratified post hoc into an inflammation group (n = 67) and a control group (n = 83) based on circulating inflammatory markers: high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), TNF-α, and IL-10. Umbilical cord blood was collected at birth, and telomere length was quantified using real-time PCR. Correlation and multivariable linear regression analyses were performed to evaluate associations between maternal inflammation and FTL. Results: Mothers in the inflammation group had significantly elevated hsCRP, IL-6, and TNF-α levels, and lower IL-10 concentrations. FTL was significantly shorter in this group compared to the controls. Unlike previous investigations that relied on single pro-inflammatory markers, our study tests a composite immune-balance index (IL-6/IL-10 ratio) together with hsCRP in a prospectively followed cohort of clinically healthy pregnancies. Using its correlation coefficient, the IL-6/IL-10 ratio alone explained approximately 28% of the total variance in fetal telomere length—almost double the variance captured by IL-6 assessed in isolation. IL-6 and hsCRP emerged as independent negative predictors of FTL in multivariable models (β = −0.37 and −0.29, respectively). The IL-6/IL-10 ratio showed the strongest inverse correlation with FTL (r = −0.53, p < 0.001). Conclusions: Subclinical systemic inflammation in late pregnancy is independently associated with shorter fetal telomere length at birth, highlighting maternal immune imbalance (especially IL-6/IL-10 ratio) as a modifiable determinant of early biological aging. These findings underscore the need to consider maternal inflammatory profiling in pregnancy as a potential target for early-life preventive strategies. Full article

Telomeres are protective DNA sequences located at chromosome ends, essential to maintaining genomic stability. This narrative review examines how maternal lifestyle factors during pregnancy influence fetal telomere length (TL). Positive associations have been identified between offspring’s TL and maternal consumption of nutrients such as vitamins C and D, folate, and magnesium. Additionally, adherence to a Mediterranean diet and regular physical activity during pregnancy are correlated with increased placental TL, supporting fetal genomic integrity. Conversely, maternal dietary patterns high in carbohydrates, fats, or alcohol, as well as exposure to triclosan and sleep-disordered breathing, negatively correlate with offspring’s TL. Maternal infections may also shorten TL through heightened inflammation and oxidative stress. However, evidence regarding the impact of other lifestyle factors—including maternal stress, smoking, caffeine intake, polyunsaturated fatty acid consumption, obesity, and sleep quality—remains inconsistent. Given that shorter telomere length has been associated with cardiovascular, pulmonary, and neurodegenerative diseases, as well as certain types of cancer, these findings highlight the vital importance of maternal health during pregnancy in order to prevent potential adverse effects on the fetus. Further studies are required to elucidate the precise timing, intensity, and interplay of these influences, enabling targeted prenatal interventions to enhance offspring health outcomes. Full article

Acute myeloid leukemia (AML) is a malignant hematological tumor with a high prevalence in elderly people, and circular RNA (circRNA) plays an important role in age-related diseases. Induction of cancer cell senescence is a highly promising therapeutic strategy; however, the presence of senescence-associated circRNAs in AML remains to be elucidated. Here, we show that the expression patterns of circRNAs differed between elderly AML patients and healthy volunteers. circSATB1 was significantly overexpressed in elderly patients and AML cells. Knockdown of circSATB1 resulted in the inhibition of proliferation and arrest of the cell cycle in the G0/G1 phase; no effect on apoptosis or DNA integrity was observed, and precocious cellular senescence was promoted, characterized by no change in telomere length. Database analysis revealed that there may be two miRNA and nine RNA-binding proteins (RBPs) involved in regulating the cellular functions of circSATB1. Our observations uncover circSATB1-orchestrated cell senescence in AML, which provides clues for finding more modest therapeutic targets for AML. Full article

Genomic instability markers are important hallmarks of aging, as previously evidenced within the European study of biomarkers of human aging, MARK-AGE; however, establishing the specific metabolic determinants of vascular aging is challenging. The objective of the present study was to evaluate the impact of the susceptibility to oxidation of serum LDL particles (LDLox) and the plasma metabolization products of nitric oxide (NOx) on relevant genomic instability markers. The analysis was performed on a MARK-AGE cohort of 1326 subjects (635 men and 691 women, 35–75 years old) randomly recruited from the general population. The Inverse Probability of Treatment Weighting causal inference algorithm was implemented in order to assess the potential causal relationship between the LDLox and NOx octile-based thresholds and three genomic instability markers measured in mononuclear leukocytes: the percentage of telomeres shorter than 3 kb, the initial DNA integrity, and the DNA damage after irradiation with 3.8 Gy. The results showed statistically significant telomere shortening for LDLox, while NOx yielded a significant impact on DNA integrity. Overall, the effect on the genomic instability markers was higher than for the confirmed vascular aging determinants, such as low HDL cholesterol levels, indicating a meaningful impact even for small changes in LDLox and NOx values. Full article

Blood bacterial DNA (BB-DNA) has been identified as a novel biomarker for metabolic dysfunction, yet its relationship with epigenetic features in type 2 diabetes mellitus (DM2) patients remains largely unexplored. This study investigated the relationship between BB-DNA and epigenetic, inflammatory, and aging-related markers in 285 elderly both with and without DM2. BB-DNA levels were higher in DM2 patients than in non-diabetic subjects, with the highest levels in those with severe renal impairment. BB-DNA showed a positive association with plasma IL-1β, linking bacterial DNA to systemic inflammation. Epigenetic analysis revealed a negative correlation between BB-DNA and DNA methylation-based leukocyte telomere length, suggesting accelerated aging in DM2. Additionally, BB-DNA was positively associated with DNAm-based biological age estimators, particularly DNAmPhenoAge and DNAmAge Skin Blood Clock. BB-DNA also correlated with DNAmVEGFA and DNAmCystatin C, key markers of diabetic nephropathy and vascular dysfunction. Furthermore, BB-DNA levels were associated with hypomethylation of genes involved in inflammation (e.g., IL1β, TNFα, IFNγ), cellular senescence (p16, p21, TP53), and metabolic regulation (e.g., IGF1, SREBF1, ABCG1, PDK4). These associations suggest that increased BB-DNA may reflect and potentially promote a pro-inflammatory and pro-senescent epigenetic profile in DM2. Importantly, many of these associations remained significant after adjusting for diabetes status, supporting BB-DNA as a robust biomarker across clinical subgroups. These findings provide new insights into the relationship between BB-DNA, inflammation, and epigenetic aging in DM2, highlighting BB-DNA as a potential biomarker for disease progression and complications, particularly in relation to renal dysfunction and systemic inflammation. Full article

Background/Objectives: This study aimed to examine the association between leukocyte telomere length (TL) measured at ages 4 and 8 and emotional and behavioral problems at age 8. We also explored whether changes in leukocyte TL between ages 4 and 8 were associated with outcomes. Methods: Data were obtained from a population-based birth cohort and included 647 children with TL at age 4 and emotional and behavioral assessments at age 8, 673 with TL and outcomes at age 8, and 315 with TL measured at both ages. TL was determined using quantitative PCR on blood samples and converted into z-scores for analysis. Emotional and behavioral problems—including internalizing, externalizing, and total difficulties—were assessed using the Strengths and Difficulties Questionnaire. Regression models were conducted using zero-inflated and negative binomial, adjusting for sociodemographic and lifestyle covariates. Results: No statistically significant associations were observed between leukocyte TL at ages 4 or 8, or TL changes over this period, and emotional and behavioral outcomes at age 8. Conclusions: Although no significant associations were found, further longitudinal research is warranted to clarify the role of TL as a potential psychobiomarker of emotional and behavioral disorders in childhood. Full article