Biomarkers Of Aging Research Articles

Modification of the telomerase gene with human regulatory sequences resets mouse telomeres to human length

Telomeres shorten with each cell division, serving as biomarkers of aging, with human tissues exhibiting short telomeres and restricted telomerase expression. In contrast, mice have longer telomeres and widespread telomerase activity, limiting their relevance as models for human telomere biology. To address this, we engineer a mouse strain with a humanized mTert gene (hmTert), replacing specific non-coding sequences with human counterparts. The hmTert gene, which is repressed in adult tissues except the gonads and thymus, closely mimics human TERT regulation. This modification rescues telomere dysfunction in mTert-knockout mice. Successive intercrosses of Terth/- mice stabilized telomere length below 10 kb, while Terth/h mice achieve a human-like average length of 10–12 kb, compared to 50 kb in wildtype mice. Despite shortened telomeres, Terth/h mice maintain normal body weight and cell homeostasis. These mice, with humanized telomere regulation, represent a valuable model to study human aging and cancer.

Protective effects and bioinformatic analysis of narciclasine on vascular aging via cross-talk between inflammation and metabolism through inhibiting skeletal muscle-specific ceramide synthase 1.

The senescence of smooth muscle is one of the independent risk factors in atherosclerosis progression in which the vascular inflammation plays an important role on vascular dysfunction. This study is designed to explore the novel vascular aging biomarkers and screen the potential molecular interventional targets through bioinformatic analysis. Transcriptional analysis was conducted based on the GSE16487 open access database, which included 15 human vascular tissue samples from two groups: young group (≤ 60 years old, n = 8) and aged group (≥ 75 years old, n = 7). There were 275 differential expression genes (119 upregulated and 156 downregulated genes) with minimum 1.5-fold change between two groups. 9 genes were mainly participated in inflammation-related signaling pathways, in which narciclasine was validated as the most effective candidate for modulation the ceramide synthesis. In vitro and animal study demonstrated that narciclasine reversed vascular aging by inhibiting skeletal muscle-specific ceramide synthase 1 (CerS1), reducing the ceramide level derived from CerS1, and improving fat deposition and circulating glycolipid metabolism. Narciclasine attenuates vascular aging and modulates the cross-talk between inflammation and metabolism via inhibiting skeletal muscle-specific ceramide synthase 1.

Greater residential greenness is associated with reduced epigenetic aging in adults

Potential pathways linking urban green spaces to improved health include relaxation, stress alleviation, and improved immune system functioning. Epigenetic age acceleration (EAA) is a composite biomarker of biological aging based on DNA methylation measurements; it is predictive of morbidity and mortality. This cross-sectional study of 116 adult residents of a metropolitan area in central North Carolina investigated associations between exposure to residential green spaces and EAA using four previously developed epigenetic age formulas. DNA methylation tests of white blood cells were conducted using Illumina MethylationEPIC v1.0 assays. EAA values were calculated as residuals from the linear regression model of epigenetic age on chronological age. Residential greenness was characterized using tree cover, total vegetated land cover, and normalized difference vegetation index (NDVI) data. An interquartile range (IQR) increase in distance-to-residence weighted average greenness within 500 m of residence was consistently associated with a reduced EAA adjusted for sociodemographic covariates, smoking status, white blood cell fractions, and the two-dimensional spline function of geographic coordinates. The reduction in the EAA estimates for the four EAA measures ranged from − 1.0 to − 1.6 years for tree cover, from − 1.2 to − 1.5 years for vegetated land cover, and from − 0.9 to − 1.3 years for the NDVI; 11 of the 12 associations were statistically significant (p < 0.05). This study produced new evidence linking reduced epigenetic aging to greater greenness near residences.

Applicability of tooth cementum thickness as an age marker: systematic review and meta-analysis.

The age estimation by tooth cementum thickness is a method that has been discussed regarding its applicability. The aim of this study was to conduct a systematic review on the use of tooth cementum thickness as a biomarker for age estimation in adults, as well as a meta-analysis to assess the method's reliability. The search was conducted on Embase, LILACS, PubMed/MEDLINE, SciELO, Scopus, and Web of Science databases. Two independent reviewers used inclusion and exclusion criteria to select and assess relevant studies. For bias risk assessment, a checklist proposed by the Joanna Briggs Institute was applied. Pearson and Spearman correlation coefficients were considered as effect measures for the meta-analysis between tooth cementum thickness and chronological age. Heterogeneity among studies was evaluated using Cochran's test ( ), I2index, and Graphic Display of Heterogeneity plot. Meta-analysis robustness was assessed using Baujat plots, and publication bias was checked using DOI plots and the Luis Furuya-Kanamori index. Most selected studies showed low risk of bias. Although not all studies were included in the meta-analysis, moderate heterogeneity was found among those included. The synthesized result indicated that tooth cementum thickness has a moderate correlation with chronological age, both when the outlier study is included ( ) and when the outlier is removed ( ). It is concluded that tooth cementum thickness represents a potential age biomarker that can be useful in age estimation methods for adults. However, the presented results should be considered cautiously, emphasizing the need for further primary studies.

A framework of biomarkers for skeletal muscle aging: a consensus statement by the Aging Biomarker Consortium

Abstract The skeletal muscle is an important organ for movement and metabolism in human body, and its physiological aging underlies the occurrence of muscle atrophy and sarcopenia. China has the largest aging population in the world and is facing a grand challenge with how to prevent and treat skeletal muscle aging-related diseases. To address this difficult problem, the Aging Biomarker Consortium (ABC) of China has reached an expert consensus on biomarkers of skeletal muscle aging by synthesizing literatures and insights from scientists and clinicians. This consensus attempts to provide a comprehensive assessment of biomarkers associated with skeletal muscle aging, and proposes a systematic framework to classify them into three dimensions: functional, structural, and humoral. Within each dimension, the experts recommend clinically relevant biomarkers for skeletal muscle aging. This consensus aims to lay the foundation for future research on skeletal muscle aging, facilitating precise prediction, diagnosis, and treatment of skeletal muscle aging and sarcopenia. It is anticipated to make significant contributions to healthy aging of skeletal muscle in the elderly population in China and around the world as well.

TimeFlies: an snRNA-seq aging clock for the fruit fly head sheds light on sex-biased aging.

Although multiple high-performing epigenetic aging clocks exist, few are based directly on gene expression. Such transcriptomic aging clocks allow us to extract age-associated genes directly. However, most existing transcriptomic clocks model a subset of genes and are limited in their ability to predict novel biomarkers. With the growing popularity of single-cell sequencing, there is a need for robust single-cell transcriptomic aging clocks. Moreover, clocks have yet to be applied to investigate the elusive phenomenon of sex differences in aging. We introduce TimeFlies, a pan-cell-type scRNA-seq aging clock for the Drosophila melanogaster head. TimeFlies uses deep learning to classify the donor age of cells based on genome-wide gene expression profiles. Using explainability methods, we identified key marker genes contributing to the classification, with lncRNAs showing up as highly enriched among predicted biomarkers. The top biomarker gene across cell types is lncRNA: roX1 , a regulator of X chromosome dosage compensation, a pathway previously identified as a top biomarker of aging in the mouse brain. We validated this finding experimentally, showing a decrease in survival probability in the absence of roX1 in vivo . Furthermore, we trained sex-specific TimeFlies clocks and noted significant differences in model predictions and explanations between male and female clocks, suggesting that different pathways drive aging in males and females.

Ultrasensitive Chemiresistive Gas Sensors Based on Dual-Mesoporous Zinc Stannate Composites for Room Temperature Rice Quality Monitoring

The integration of dual-mesoporous structures, the construction of heterojunctions, and the incorporation of highly concentrated oxygen vacancies are pivotal for advancing metal oxide-based gas sensors. Nonetheless, achieving an optimal design that simultaneously combines mesoporous structures, precise heterojunction modulation, and controlled oxygen vacancies through a one-step process remains challenging. This study proposes an innovative method for fabricating zinc stannate semiconductors featuring dual-mesoporous structures and tunable oxygen vacancies via a direct solution precursor plasma spray technique. As a proof of concept, the resulting zinc stannate-based coatings are applied to detect 2-undecanone, a key biomarker for rice aging. Remarkably, the zinc oxide/zinc stannate heterojunctions with a well-defined secondary pore structure exhibit exceptional gas-sensing performance for 2-undecanone at room temperature. Furthermore, practical experiments indicate that the developed sensor effectively identifies adulteration in various rice varieties. These results underscore the potential of this method for designing metal oxides with tailored properties for high-performance gas sensors. The enhanced adsorption capacity and dual-mesoporous features of this semiconductor make it a promising candidate for sensing applications in agricultural food safety inspections.

Differential Gene Expression Analysis of Whole Blood Transcriptome Between Young and Old Border Collie Dogs

Aging is the most significant risk factor for many diseases and increased mortality, and it is influenced by both genetic and environmental factors. In this study, our primary goal was to investigate age-related gene expression changes in whole blood samples collected from dogs and identify potential biomarkers of healthy aging. We sequenced the mRNA fraction of whole blood samples from five young and five old border collie dogs and performed differential gene expression and differential transcript usage analyses. The raw sequencing data exhibited high quality. Multidimensional scaling analysis failed to differentiate age clusters. Moreover, we identified only a limited number of differentially expressed genes (n = 61) and 30 genes with differential transcript usage between the blood transcriptomes of young and old dogs. Our results align with publicly available data on dogs. However, studies on other species, such as wolves, have identified more significant age-related genes. In conclusion, while some of our findings are promising, further research is needed to standardize environmental factors affecting blood gene expression levels in dogs. Additionally, we recommend implementing pre-sequencing hemoglobin depletion to improve the analysis of whole blood in future studies.

Age-Related Changes in Caudate Glucose Metabolism: Insights from Normative Modeling Study in Healthy Subjects

Background: As the global population ages, the prevalence of neurodegenerative conditions, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), dementia with Lewy bodies, and frontotemporal dementia, continues to rise. Understanding the impact of aging on striatal glucose metabolism is pivotal in identifying potential biomarkers for the early detection of these disorders. Methods: We investigated age-related changes in striatal glucose metabolism using both region of interest (ROI)-based and voxel-wise correlation analyses. Additionally, we employed a normative modeling approach to establish age-related metabolic trajectories and assess individual deviations from these normative patterns. In vivo cerebral glucose metabolism was quantified using a molecular neuroimaging technique, 18F-FDG PET. Results: Our results revealed significant negative correlations between age and glucose metabolism in the bilateral caudate. Furthermore, the normative modeling demonstrated a clear, progressive decline in caudate metabolism with advancing age, and the most pronounced reductions were observed in older individuals. Conclusions: These findings suggest that metabolic reductions in the caudate may serve as a sensitive biomarker for normal aging and offer valuable insights into the early stages of neurodegenerative diseases. Moreover, by establishing age-specific reference values for caudate glucose metabolism, the normative model provides a framework for detecting deviations from expected metabolic patterns, which may facilitate the early identification of metabolic alterations that could precede clinical symptoms of neurodegenerative processes.

Mineral Stress Drives Loss of Heterochromatin: An Early Harbinger of Vascular Inflammaging and Calcification.

Vascular calcification is a detrimental aging pathology markedly accelerated in patients with chronic kidney disease. Prelamin A is a biomarker of vascular smooth muscle cell aging that accelerates calcification however the mechanisms remain undefined. Vascular smooth muscle cells were transduced with prelamin A using an adenoviral vector and epigenetic modifications were monitored using immunofluorescence and targeted polymerase chain reaction array. Epigenetic findings were verified in vivo using immunohistochemistry in human vessels, in a mouse model of inducible prelamin A expression, and in a rat model of chronic kidney disease-induced calcification. Transcriptomic and chromatin immunoprecipitation followed by sequencing analyses were used to identify gene targets impacted by changes in the epigenetic landscape. Molecular tools and antibody arrays were used to monitor the effects of mineral dysregulation on heterochromatin, inflammation, aging, and calcification. Here, we report that depletion of the repressive heterochromatin marks, H3K9me3 and H3K27me3, is an early hallmark of vascular aging induced by both nuclear lamina dysfunction and dysregulated mineral metabolism, which act to modulate the expression of key epigenetic writers and erasers. Global analysis of H3K9me3 and H3K27me3 marks and pathway analysis revealed deregulation of insulin signaling and autophagy pathways as well as cross-talking DNA damage and NF-κB (nuclear factor κB) inflammatory pathways consistent with early activation of the senescence-associated secretory phenotype. Expression of prelamin A in vivo induced loss of heterochromatin and promoted inflammation and osteogenic differentiation which preceded aging indices, such as DNA damage and senescence. Vessels from children on dialysis and rats with chronic kidney disease showed prelamin A accumulation and accelerated loss of heterochromatin before the onset of calcification. Dysregulated mineral metabolism drives changes in the epigenetic landscape and nuclear lamina dysfunction that together promote early induction of inflammaging pathways priming the vasculature for downstream pathological change.

Combination of Biological Aging and Genetic Susceptibility Helps Identifying At-Risk Population of Venous Thromboembolism: A Prospective Cohort Study of 394 041 Participants.

Phenotypic age acceleration (PhenoAgeAccel) is a novel clinical aging indicator. This study was carried out to investigate the relationship between PhenoAgeAccel and the incidence of VTE, as well as to integrate PhenoAgeAccel with genetic susceptibility to improve risk stratification of VTE. The study included 394 041 individuals from the UK Biobank. Phenotypic age was calculated based on actual age and clinical biomarkers. PhenoAgeAccel presents the residual obtained from a linear regression of phenotypic age against actual age, reflecting the rate of aging. Significant associations were observed between PhenoAgeAccel and higher risk of VTE (Hazard ratio [HR] 1.37, 95% CI: 1.32-1.42), deep vein thrombosis (DVT, HR 1.35, 95% CI: 1.29-1.42), and PE (pulmonary embolism, HR 1.41, 95% CI: 1.34-1.48) in the findings. PhenoAgeAccel exhibited a significant additive interaction with genetic susceptibility. Biologically older participants with high genetic risk have a 3.83 (95% CI: 3.51-4.18) folds risk of VTE, a 3.59 (95% CI: 3.21-4.03) folds risk of DVT, and 4.39 (95% CI: 3.88-4.98) folds risk of PE, in comparison to biologically younger participants with low genetic risk. Mediation analyses indicated that PhenoAgeAccel mediated approximately 6% of the association between cancer and VTE, and about 20% of the association between obesity and VTE. Our study indicated that PhenoAgeAccel is significantly associated with higher risk of VTE, and can be combined with genetic risk to improve VTE risk stratification. Additionally, PhenoAgeAccel holds promise as a clinical biomarker for guiding targeted prevention and treatment strategies for VTE.

Placental trophoblast aging in advanced maternal age is related to increased oxidative damage and decreased YAP.

The advanced maternal age (AMA) pregnancies escalate rapidly, which are frequently linked to higher risks of adverse outcomes. Advanced maternal age (AMA) placenta exhibited premature aging, presumably resulting in trophoblast dysfunction, inadequate placentation. However, the precise reasons and mechanisms of trophoblast aging in AMA placenta remain unclear, posing a significant limitation to provide effective guidance for prenatal healthcare in clinical settings. Notably, the organism shows heightened vulnerability to oxidative damage as it ages. YAP (Yes-associated protein) was reported to play a critical role in regulation of aging and resisting oxidative damage, yet these roles had not been elucidated in the placenta. Therefore, this study explored the relationship between trophoblast cell aging and oxidative injury and YAP in AMA pregnancy, which not only provided an insight into the mechanisms of trophoblast cell aging, but also provide valuable directions for healthcare during AMA pregnancy. In this study, human term placentas were collected from AMA and normal pregnancies for the analysis of aging, oxidative damage and YAP level. HTR8/SVneo cells were manipulated with (hydrogen peroxide) H2O2 to explore the effects of oxidative damage on trophoblast cell senescence and YAP levels. YAP expression in HTR8/SVneo cells was manipulated to investigate its role in trophoblastic senescence and oxidative damage. Compared with the control group, the AMA placenta exhibits increased aging biomarkers, which is coupled with an elevation in oxidative damage within placental trophoblast cells and a notable decline in YAP levels. Cellular experiments demonstrated that oxidative damage from H2O2 triggered trophoblast cell senescence and resulted in a reduction of YAP levels. Furthermore, employing molecular modification to silence YAP expression in these cells led to an induction of aging. Conversely, overexpressing YAP ameliorated both trophoblast cell aging and the associated DNA oxidative damage that arised from H2O2. The decline of YAP in AMA pregnancy should be responsible for the increased oxidative injury and premature placenta aging, indicating that YAP plays a significant role in combating oxidative damage and delaying aging, thereby providing a new guidance for prenatal care in AMA pregnancies. Maintaining YAP levels or implementing anti-oxidative stress interventions could potentially mitigate the incidence of complications involved AMA pregnancy.

DNA methylation clocks struggle to distinguish inflammaging from healthy aging, but feature rectification improves coherence and enhances detection of inflammaging.

Biological age estimation from DNA methylation and determination of relevant biomarkers is an active research problem which has predominantly been tackled with black-box penalized regression. Machine learning is used to select a small subset of features from hundreds of thousands of CpG probes and to increase generalizability typically lacking with ordinary least-squares regression. Here, we show that such feature selection lacks biological interpretability and relevance in the clocks of the first and next generations and clarify the logic by which these clocks systematically exclude biomarkers of aging and age-related disease. Moreover, in contrast to the assumption that regularized linear regression is needed to prevent overfitting, we demonstrate that hypothesis-driven selection of biologically relevant features in conjunction with ordinary least squares regression yields accurate, well-calibrated, generalizable clocks with high interpretability. We further demonstrate that the interplay of inflammaging-related shifts of predictor values and their corresponding weights, which we term feature shifts, contributes to the lack of resolution between health and inflammaging in conventional linear models. Lastly, we introduce a method of feature rectification, which aligns these shifts to improve the distinction of age predictions for healthy people vs. patients with various chronic inflammation diseases.

Characterizing biomarkers of ageing in Singaporeans: the ABIOS observational study protocol.

Ageing is the primary driver of age-associated chronic diseases and conditions. Asian populations have traditionally been underrepresented in studies understanding age-related diseases. Thus, the Ageing BIOmarker Study in Singaporeans (ABIOS) aims to characterise biomarkers of ageing in Singaporeans, exploring associations between molecular, physiological, and digital biomarkers of ageing. This is a single-centre, cross-sectional study that recruits healthy community-dwelling adults (≥ 21 years) from three different ethnic groups (Chinese, Malay, and Indian). Molecular biomarkers of ageing include multi-omics approaches, such as DNA methylation analysis and metabolic and inflammatory proteomic profiling in blood, saliva, and stool. Physiological biomarkers of ageing include bone density, body composition, skin autofluorescence, arterial stiffness, physical performance (e.g., muscle strength and flexibility), cognition, and nutritional status. Digital biomarkers of ageing include three-dimensional facial morphology and objectively measured physical activity. Additional measures, such as habitual physical activity, dietary patterns, and medical history, are also examined. The associations between the molecular, physiological, and digital phenotypes will be explored. This study is expected to generate a comprehensive profile of molecular, physiological, and digital biomarkers of ageing in Chinese, Malay, and Indian populations in Singapore. By integrating diverse age-related biomarkers, clinical indicators, and lifestyle factors, ABIOS will offer unique insights into the ageing process specific to Southeast Asian populations. These findings can help identify markers of biological ageing, uncover ethnic-specific patterns, and reveal modifiable lifestyle factors for healthier ageing. The results could inform evidence-based health policies, personalized interventions, and future cross-ethnic comparative studies to enhance understanding of ageing biology across diverse populations.

Beneficial Effects of a Moderately High-Protein Diet on Telomere Length in Subjects with Overweight or Obesity.

Telomere length (TL) is a key biomarker of cellular aging, with shorter telomeres associated with age-related diseases. Lifestyle interventions mitigating telomere shortening are essential for preventing such conditions. This study aimed to examine the effects of two weight loss dietary strategies, based on a moderately high-protein (MHP) diet and a low-fat (LF) diet on TL in individuals with overweight or obesity. A total of 164 participants, aged 18-65 years from the OBEKIT trial received the MHP (n = 83) or the LF diet (n = 81) for 4 months and had TL data for analyses. TL was measured at baseline and after 4 months of the intervention using monochrome multiplex quantitative polymerase chain reaction (MMqPCR). Both groups experienced significant improvements in anthropometric and biochemical parameters after the dietary intervention (p < 0.001). The MHP group showed an increase in TL (+0.16 ± 0.13) compared to the LF group (-0.05 ± 0.13) in multiple-adjusted models (p = 0.016). An interaction was observed between the sex and dietary group, where women in the MHP group had increased TL (+0.23 ± 0.16) after 4 months compared to women in the LF group (-0.13 ± 0.15; p = 0.001); no differences between dietary groups were found in men. This increase in TL for women was associated with an increase in protein intake (p = 0.006), measured through dietary questionnaires. This study shows that a MHP diet may have a protective effect on TL during weight loss, particularly in women, potentially contributing to healthier aging. These results highlight the importance of considering macronutrient composition in dietary interventions aimed at preserving TL.

Examining the Relationship Between Weekend Catch-Up Sleep and Phenotypic Age Acceleration: Insights From a Cross-Sectional Study.

Phenotypic age acceleration (PhenoAgeAccel) is a potential aging biomarker. While weekend catch-up sleep (WCS) is commonly practiced to compensate for weekday sleep deficits, its relationship with PhenoAgeAccel remains unclear. In this cross-sectional study, we analyzed data from 7 683 participants in the National Health and Nutrition Examination Survey. WCS duration was calculated as weekend sleep duration minus weekday sleep duration, and WCS was further defined as WCS duration >0 hour. Multivariable logistic regression adjusted for confounders and subgroup analyses by weekday sleep duration were employed to examine the relationship of WCS with PhenoAgeAccel. WCS is associated with a modulated risk of PhenoAgeAccel, contingent on the amount of WCS and regular weekday sleep. Specifically, engaging in 0-1 hour of WCS was associated with significantly lower odds of PhenoAgeAccel (odds ratio = 0.80, 95% confidence interval: 0.68-0.94, p = .007) compared to no WCS, particularly among individuals who averaged 7-8 hours of sleep on weekdays (odds ratio = 0.67, 95% confidence interval: 0.49-0.93, p = .016). Conversely, those sleeping less than 6 hours on weekdays benefited from extending WCS beyond 2 hours (odds ratio = 0.65, 95% confidence interval: 0.44-0.97, p = .036). No benefits were observed for those with more than 8 hours of weekday sleep. WCS is associated with a reduced likelihood of PhenoAgeAccel among individuals with inadequate weekday sleep, particularly those sleeping less than 6 hours or between 7 and 8 hours on weekdays.

Development and Validation of a Predictive Model Based on Serum Silent Information Regulator 6 Levels in Chinese Older Adult Patients: Cross-Sectional Descriptive Study.

Serum levels of silent information regulator 6 (SIRT6), a key biomarker of aging, were identified as a predictor of coronary artery disease (CAD), but whether SIRT6 can distinguish severity of coronary artery lesions in older adult patients is unknown. This study developed a nomogram to demonstrate the functionality of SIRT6 in assessing severity of coronary artery atherosclerosis. Patients aged 60 years and older with angina pectoris were screened for this single-center clinical study between October 1, 2022, and March 31, 2023. Serum specimens of eligible patients were collected for SIRT6 detection by enzyme-linked immunosorbent assay. Clinical data and putative predictors, including 29 physiological characteristics, biochemical parameters, carotid artery ultrasonographic results, and complete coronary angiography findings, were evaluated, with CAD diagnosis as the primary outcome. The nomogram was derived from the Extreme Gradient Boosting (XGBoost) model, with logistic regression for variable selection. Model performance was assessed by examining discrimination, calibration, and clinical use separately. A 10-fold cross-validation technique was used to compare all models. The models' performance was further evaluated on the internal validation set to ensure that the obtained results were not due to overoptimization. Eligible patients (n=222) were divided into 2 cohorts: the development cohort (n=178) and the validation cohort (n=44). Serum SIRT6 levels were identified as both an independent risk factor and a predictor for CAD in older adults. The area under the receiver operating characteristic curve (AUROC) was 0.725 (95% CI 0.653-0.797). The optimal cutoff value of SIRT6 for predicting CAD was 546.384 pg/mL. Predictors included in this nomogram were serum SIRT6 levels, triglyceride glucose (TyG) index, and apolipoprotein B. The model achieved an AUROC of 0.956 (95% CI 0.928-0.983) in the development cohort. Similarly, in the internal validation cohort, the AUROC was 0.913 (95% CI 0.828-0.999). All models demonstrated satisfactory calibration, with predicted outcomes closely aligning with actual results. SIRT6 shows promise in predicting CAD, with enhanced predictive abilities when combined with the TyG index. In clinical settings, monitoring fluctuations in SIRT6 and TyG may offer valuable insights for early CAD detection. The nomogram for CAD outcome prediction in older adult patients with angina pectoris may aid in clinical trial design and personalized clinical decision-making, particularly in institutions where SIRT6 is being explored as a biomarker for aging or cardiovascular health.

Klotho protein: A key modulator of aging and COVID-19 severity.

The COVID-19 pandemic has drawn significant attention to factors affecting disease severity, especially in older adults. This study explores the relationship between Klotho, an anti-aging protein, and COVID-19 severity. Conducted at Tehran's Firouzgar Hospital, this case-control study involved 279 participants, assessing serum levels of Klotho, inflammatory markers (C-reactive protein (CRP), Interleukin 6 (IL-6)), and Vitamin D. The findings indicate significantly lower Klotho levels in COVID-19 patients, especially those in the ICU, which correlate with elevated inflammatory markers and reduced Vitamin D levels. This inverse relationship between Klotho levels and disease severity underscores the protein's potential modulatory role in the inflammatory response to COVID-19. The study not only highlights the importance of Klotho as a biomarker for aging and disease severity but also suggests its potential therapeutic value in managing COVID-19, offering a novel perspective on targeting aging-related pathways to mitigate the impact of the disease. These insights open new avenues for research and intervention strategies to leverage anti-aging mechanisms to combat COVID-19 and potentially other age-related diseases.

Identify biological Alzheimer's disease using a novel nucleic acid-linked protein immunoassay.

Blood-based biomarkers have been revolutionizing the detection, diagnosis and screening of Alzheimer's disease. Specifically, phosphorylated-tau variants (p-tau181, p-tau217 and p-tau231) are promising biomarkers for identifying Alzheimer's disease pathology. Antibody-based assays such as single molecule arrays immunoassays are powerful tools to investigate pathological changes indicated by blood-based biomarkers and have been studied extensively in the Alzheimer's disease research field. A novel proteomic technology-NUcleic acid Linked Immuno-Sandwich Assay (NULISA)-was developed to improve the sensitivity of traditional proximity ligation assays and offer a comprehensive outlook for 120 protein biomarkers in neurodegenerative diseases. Due to the relative novelty of the NULISA technology in quantifying Alzheimer's disease biomarkers, validation through comparisons with more established methods is required. The main objective of the current study was to determine the capability of p-tau variants quantified using NULISA for identifying abnormal amyloid-β and tau pathology. We assessed 397 participants [mean (standard deviation) age, 64.8 (15.7) years; 244 females (61.5%) and 153 males (38.5%)] from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort where participants had plasma measurements of p-tau181, p-tau217 and p-tau231 from NULISA and single molecule arrays immunoassays. Participants also underwent neuroimaging assessments, including structural MRI, amyloid-PET and tau-PET. Our findings suggest an excellent agreement between plasma p-tau variants quantified using NULISA and single molecule arrays immunoassays. Plasma p-tau217 measured with NULISA shows excellent discriminative accuracy for abnormal amyloid-PET (area under the receiver operating characteristic curve = 0.918, 95% confidence interval = 0.883 to 0.953, P < 0.0001) and tau-PET (area under the receiver operating characteristic curve = 0.939; 95% confidence interval = 0.909 to 0.969, P < 0.0001). It also presents the capability for differentiating tau-PET staging. Validation of the NULISA-measured plasma biomarkers adds to the current analytical methods for Alzheimer's disease diagnosis, screening and staging and could potentially expedite the development of a blood-based biomarker panel.

One-carbon metabolism-related compounds are associated with epigenetic aging biomarkers: Results from National Health and Nutrition Examination Survey (NHANES) 1999-2002.

One-carbon metabolism (OCM), a biochemical pathway dependent on micronutrients including folate and vitamin B12, plays an essential role in aging-related physiological processes. DNA methylation-based aging biomarkers may be influenced by OCM. This study investigated associations of OCM-related biomarkers with epigenetic aging biomarkers in the National Health and Nutrition Examination Survey (NHANES). Blood DNA methylation was measured in adults aged ≥50 years in the 1999-2000 and 2001-2002 cycles of NHANES. The following epigenetic aging biomarkers were included: Horvath1, Horvath2, Hannum, PhenoAge, GrimAge2, DunedinPoAm, and DNA methylation telomere length (DNAmTL). We tested for associations of serum folate, red blood cell (RBC) folate, vitamin B12, homocysteine, and methylmalonic acid concentrations with epigenetic age deviation (EAD) among 2,346 participants with epigenetic and nutritional status biomarkers using survey weighted general linear regression models adjusting for sociodemographics, BMI, and behavioral factors. A doubling of serum folate concentration was associated with -0.82 years (95% confidence interval (CI) = -1.40, -0.23) lower GrimAge EAD, -0.13 SDs (-0.22, -0.03) lower DunedinPoAm, and 0.02 kb (0.00, 0.04) greater DNAmTL EAD. Associations were attenuated after adjusting for smoking status and alcohol intake, folate antagonists. Conversely, a doubling in homocysteine concentration was associated with 1.05 years (0.06, 2.04) greater PhenoAge EAD, 1.93 years (1.16, 2.71) greater GrimAge2 EAD, and 0.26 SDs (0.10, 0.41) greater DunedinPoAm. Associations with GrimAge2 EAD and DunedinPoAm were robust to alcohol and smoking adjustment. In a nationally representative sample of U.S. adults, greater folate, a carbon donor, was associated with lower EAD, and greater homocysteine, an indicator of OCM deficiencies, was associated with greater EAD; however, some associations were influenced by smoking status. Future research should focus on high-risk populations. Randomized controlled trials with long-term follow-up are also needed to established causality and investigate the clinical relevance of changes in EAD.