Clinical biomarker-based biological aging and risk of benign prostatic hyperplasia: A large prospective cohort study.

Objective: Chronological age (CAge), biological age (BAge), and accelerated age (AAge) are all important for aging-related diseases. CAge is a known risk factor for benign prostatic hyperplasia (BPH); However, the evidence of association of BAge and AAge with BPH is limited. This study aimed to evaluate the association of CAge, Bage, and AAge with BPH in a large prospective cohort. Method: A total of 135,933 males without BPH at enrolment were extracted from the UK biobank. We calculated three BAge measures (Klemera-Doubal method, KDM; PhenoAge; homeostatic dysregulation, HD) based on 16 biomarkers. Additionally, we calculated KDM-BAge and PhenoAge-BAge measures based on the Levine method. The KDM-AAge and PhenoAge-AAge were assessed by the difference between CAge and BAge and were standardized (mean = 0 and standard deviation [SD] = 1). Cox proportional hazard models were applied to assess the associations of CAge, Bage, and AAge with incident BPH risk. Results: During a median follow-up of 13.150 years, 11,811 (8.690%) incident BPH were identified. Advanced CAge and BAge measures were associated with an increased risk of BPH, showing threshold effects at a later age (all P for nonlinearity <0.001). Nonlinear relationships between AAge measures and risk of BPH were also found for KDM-AAge (P = 0.041) and PhenoAge-AAge (P = 0.020). Compared to the balance comparison group (-1 SD < AAge < 1 SD), the accelerated aging group (AAge > 2 SD) had a significantly elevated BPH risk with hazard ratio (HR) of 1.115 (95% CI, 1.000-1.223) for KDM-AAge and 1.180 (95% CI, 1.068-1.303) for PhenoAge-AAge, respectively. For PhenoAge-AAge, subgroup analysis of the accelerated aging group showed an increased HR of 1.904 (95% CI, 1.374-2.639) in males with CAge <50 years and 1.233 (95% CI, 1.088-1.397) in those having testosterone levels <12 nmol/L. Moreover, AAge-associated risk of BPH was independent of and additive to genetic risk. Conclusions: Biological aging is an independent and modifiable risk factor for BPH. We suggest performing active health interventions to slow biological aging, which will help mitigate the progression of prostate aging and further reduce the burden of BPH.

Deciphering the Biological Ageing Impact on Alveolar Bone Loss: Insights from α-Klotho and Renal Function Dynamics.

Alveolar bone loss is generally considered as a chronological age-related disease. As biological ageing process is not absolutely determined by increasing age, whether alveolar bone loss associated with increasing chronological age or biological ageing remains unclear. Accurately distinguishing whether alveolar bone loss is chronological age-related or biological ageing-related is critical for selecting appropriate clinical treatments. This study aimed to identify the relationship between alveolar bone loss and body ageing. 3635 participants from National Health and Nutrition Examination Survey and 71 living kidney transplant recipients from Gene Expression Omnibus Datasets were enrolled. Multivariate regression analysis, smooth curve fittings and generalized additive models were used to explore the association among alveolar bone loss, age, serum α-Klotho level, renal function markers, as well as between preoperative creatinine and renal cortex related α-Klotho gene expression level. Meanwhile, a two-sample Mendelian randomization study was conducted to assess the causal relationship between α-Klotho and periodontal disease (4,376 individuals versus 361,194 individuals). As biological ageing related indicator, α-Klotho level was negatively correlated with impaired renal function and alveolar bone loss. Correspondingly, accompanied by decreasing renal function, it was manifested with down-regulated expression level of α-Klotho in renal cortex and aggravated alveolar bone loss. The MR analysis further identified the negative association between higher genetically predicted α-Klotho concentrations with alveolar bone loss susceptibility using the IVW (OR=0.999, P=0.005). However, an inversely U-shaped association was observed between chronological age and alveolar bone loss, which especially stable in men (the optimal cut-off values were both 62 years old). For male above 62 years old, increasing age converted to protective factor and accompanied by alleviated alveolar bone loss. Alveolar bone loss which directly associated to decreased renal function and α-Klotho level was related to biological ageing rather than chronological age. The renal-alveolar bone axis could provide new sight of clinical therapy in alveolar bone loss.

Radiological Evaluation of the Accuracy of Demirjian, Nolla, and Willems Methods for Dental Age Estimation in 3-17-Year-Old Iranian Children.

Background: The stage of tooth formation is one of the most reliable indicators for predicting a patient's developmental age by radiographs. This study compared the accuracy of three distinct dental age estimation methods (Demirjian, Nolla, and Willems) in children aged 3-17 in the northern Iranian population. Methods: This cross-sectional study examined panoramic radiographs of 434 children aged 3-17 from Mazandaran Province, Iran, who had teeth 31-37 present on the left mandible. This study employed the Demirjian, Nolla, and Willems methods to estimate the dental age of the sample and compare it with the chronological age. The data were analyzed using SPSS v16. A paired t-test was used to compare chronological and dental ages. The Pearson correlation was used to correlate the chronological and dental ages. The errors of different methods were compared using the Wilcoxon test. P values < 0.05 were considered significant for all tests except Wilcoxon. For Wilcoxon, a P value < 0.017 was considered significant. Results: The three methods presented differing mean estimated ages. The Demirjian method delivered the highest mean, and all three methods differed significantly when compared in pairs. The results showed that the Demirjian method overestimated chronological age by 0.25 years (P < 0.001) in girls and 0.09 years (P = 0.28) in boys. The Willems method underestimated chronological age by 0.05 years (P = 0.47) in girls and 0.12 years (P = 0.13) in boys. The Nolla method underestimated chronological age by 0.41 years (P < 0.001) in girls and 0.40 years (P < 0.001) in boys. The accuracy of each method varied with the patient's age. Conclusion: According to the findings, the Willems method outperformed the Demirjian method, and the Demirjian method exceeded the Nolla method for estimating dental age in Iranian children aged 3-17. Overall, the Demirjian method overestimated the age of the study population, whereas the other two underestimated it.

Mitigating against relative age effects in youth Track & Field: Validating corrective adjustment procedures across multiple events.

OBJECTIVES: With the aim to better identify talented Track & Field performance development, this study estimated the relationships between chronological (decimal) age with 60-m sprint, high jump, triple jump, and pole vault performance. Then, to mitigate against expected Relative Age Effects (RAEs), Corrective Adjustment Procedures (CAPs) were applied to an independent sample. DESIGN: Mixed-longitudinal design examining public data between 2005 and 2019. METHODS: The performances of 5339 Italian sprinters and jumpers (53.1 %) spanning 11.01-17.99 years of age were examined, with trendlines between chronological age and performance established. Related to an independent sample (N = 40,306; female 45.5 %), trendlines were then utilised to apply CAPs and adjust individual performance. Considering raw and adjusted performance data, RAE distributions were examined for the top 25 % and 10 % performers. RESULTS: For all male and female events, quadratic models best summarised the relationships between chronological age and performance (R2 = 0.74-0.89). When examining independent athletes in similar event, RAEs were more pronounced in males (Cramer's V = 0.35-0.14) than females (Cramer's V = 0.29-0.07). For both sexes, RAE magnitude decreased with age and increased according to performance level (i.e., Top25%-Top10%). However, following CAP applications, RAEs were reduced or removed within annual age groups and performance levels. CONCLUSIONS: With RAEs prevalent across Italian youth Track & Field events, findings validate CAPs as a strategy to account for the influence of relative age differences on athletic performance. CAPs help establish a more equitable strategy for performance evaluation and could help improve the efficacy of long-term athlete development programming.

Association between biological aging and diabetic retinopathy.

The impact of aging on diabetic retinopathy (DR) remains underestimated. The current study aimed to investigate the association between biological aging and DR, in contrast to chronological age (CA). Using the National Health and Nutrition Survey data from 2005 to 2008. Biological aging was evaluated through the biological age (BA) and phenotypic age (PA), which were calculated from clinical markers. DR was identified in participants with diabetes mellitus (DM) when they exhibited one or more retinal microaneurysms or retinal blot hemorrhages under retinal imaging, with or without the presence of more severe lesions. Survey-weighted multivariable logistic regression was performed, and the regression model was further fitted using restricted cubic splines. The discriminatory capability and clinical utility of the model were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Based on weighted analyses, of the 3100 participants included in this study, of which 162 had DR. In the adjusted model, BA (odds ratio [OR] = 1.12, 95% CI, 1.06-1.18) and PA (OR = 1.11, 95% CI, 1.07-1.14) were associated with DR, while CA was not significantly (OR = 1.01, 95% CI, 0.99-1.03). Narrowing the analysis to DM participants and adjusting for factors like insulin showed similar results. ROC and DCA analyses indicate that BA/PA predicted DR better than CA and offer greater clinical utility. The positive association between BA/PA and DR was consistent across subgroups despite potential interactions. Biological aging heightens DR risk, with BA/PA showing a stronger association than CA. Our findings underscored the importance of timely anti-aging interventions for preventing DR.

Age-related patterns in mandibular third molar eruption: presenting new forensic age assessment reference data from a Chinese population.

Valid reference data are essential for reliable forensic age assessment procedures in the living, a fact that extends to the trait of mandibular third molar eruption in dental panoramic radiographs (PAN). The objective of this study was to acquire valid reference data for a northern Chinese population. The study was guided by the criteria for reference studies in age assessment.To this end, a study population from China comprising 917 panoramic radiographs obtained from 430 females and 487 males aged between 15.00 and 25.99 years was analysed. Of the 917 PANs, a total of 1230 mandibular third molars were evaluated.The PANs, retrospectively evaluated, were performed for medical indication during the period from 2016 to 2021. The assessment of mandibular third molars was conducted using the staging scale presented by Olze et al. in 2012. Two independent examiners, trained in assessing PANs for forensic age estimation, evaluated the images. In instances where the two examiners diverged in their assessments these were subsequently deliberated, and a consensus stage was assigned.The mean age increased with higher stages for both teeth and both sexes. The minimum age recorded for stage D, indicating complete tooth eruption, was 15.6 years in females and 16.1 years in males. Consequently, the completion of mandibular third molar eruption was observed in both sexes well before reaching the age of 18. In light of our results, it is evident that relying solely on the assessment of mandibular third molar eruption may not be sufficient for accurately determining the age of majority. Contrary to previous literature, this finding of a completed eruption of the mandibular third molars in northern Chinese individuals is only suitable for detecting the completion of the 16th year of life in males according to our results. However, as the results are inconsistent compared to other studies in the literature, the trait should not be used as the only decisive marker to prove this age threshold in males from northern China.

Studying eruption patterns of mandibular third molars for forensic age assessment: Introducing current reference data from a population of black South Africans.

INTRODUCTION: Evaluation of the eruption of mandibular third molars in orthopantomograms (OPGs) is a method of forensic age assessment. The objective of our study was to provide valid reference data for this trait within a population of black South Africans. The study was guided by the criteria for reference studies in age assessment. MATERIALS AND METHODS: A study population from Pretoria, South Africa comprising 670 OPGs obtained from 338 black females and 332 black males aged between 15.00 and 25.97 years was analysed. All OPGs were performed for medical indication during the period from 2011 to 2022 and were retrospectively evaluated. From the 670 OPGs, a total of 1021 mandibular third molars were evaluated. The assessment of mandibular third molars was conducted using the staging scale presented by Olze et al. in 2012. Two experienced dentists evaluated the OPGs independently of each other. If the two examiners diverged in their assessments, a consensus stage was assigned. RESULTS: As expected, the mean, median and minimal age increased with higher stages for both teeth and both sexes. The minimum age recorded for stage D, indicating complete tooth eruption, was 15.79 years in females and 16.62 years in males. CONCLUSION: As it is the case for previous reference studies in other countries, placing exclusive reliance on the evaluation of mandibular third molar eruption is inadequate for ascertaining the age of majority among Black South Africans. Future studies need to examine if our results are transferable to other countries in Sub-Saharan Africa.

TAVR in Older Adults: Moving Toward a Comprehensive Geriatric Assessment and Away From Chronological Age: JACC Family Series.

Calcific aortic stenosis can be considered a model for geriatric cardiovascular conditions due to a confluence of factors. The remarkable technological development of transcatheter aortic valve replacement was studied initially on older adult populations with prohibitive or high-risk for surgical valve replacement. Through these trials, the cardiovascular community has recognized that stratification of these chronologically older adults can be improved incrementally by invoking the concept of frailty and other geriatric risks. Given the complexity of the aging process, stratification by chronological age should only be the initial step but is no longer sufficient to optimally quantify cardiovascular and noncardiovascular risk. In this review, we employ a geriatric cardiology lens to focus on the diagnosis and the comprehensive management of aortic stenosis in older adults to enhance shared decision-making with patients and their families and optimize patient-centered outcomes. Finally, we highlight knowledge gaps that are critical for future areas of study.

Bone Age Determination of Epiphyseal Fusion at Knee Joint and Its Correlation with Chronological Age.

Background and Objectives: Bone age determination is a valuable method for forensic and disaster identifications of unknown human remains, as well as for medical and surgical procedural purposes. This retrospective research study aimed to determine the age based on epiphyseal fusion stages and investigate differences related to gender. Materials and Methods: X-rays of the knee were collected from medical imaging centers in hospitals in the south of Jordan and examined by two observers who determined the bone epiphyseal phase of closure for the femur, tibia, and fibula bone ends close to the knee based on a three-stage classification. Results: The main results revealed that females showed earlier epiphyseal union (Stage II) at the lower end of the femur and the upper ends of the tibia and fibula compared to males. In males, the start of complete union (Stage III) at knee bones was seen at the age of 17-18 years, while in females, it was seen at the age of 16-17 years. Additionally, knee bones showed complete union in 100% of males and females in the age groups 21-22 years and 20-21 years, respectively. Although females showed an earlier start and end of epiphyseal complete union than males, analysis of collected data showed no significant age differences between males and females at the three stages of epiphyseal union of the knee bones. Conclusions: Findings of the radiographic analysis of bone epiphyseal fusion at the knee joint are a helpful method for chronological age determination. This study supports the gender and ethnicity variation among different geographical locations. Studies with a high sample number would be needed to validate our findings.

Third molar eruption in dental panoramic radiographs as a feature for forensic age assessment - new reference data from a German population.

Forensic age assessment in the living can provide legal certainty when an individual's chronological age is unknown or when age-related information is questionable. An established method involves assessing the eruption of mandibular third molars through dental panoramic radiographs (PAN). In age assessment procedures, the respective findings are compared to reference data. The objective of this study was to generate new reference data in line with the required standards for mandibular third molar eruption within a German population. For this purpose, 605 PANs from 302 females and 303 males aged 15.04 to 25.99 years were examined. The PANs were acquired between 2013 and 2020, and the development of the mandibular third molars was rated independently by two experienced examiners using the Olze et al. staging scale from 2012. In case of disagreement in the assigned ratings, a consensus was reached through arbitration. While the mean, median and minimum ages were observed to increase with each stage of mandibular third molar eruption according to the Olze method, there was considerable overlap in the distribution of age between the stages. The minimum age for stage D, which corresponds to complete tooth eruption, was 16.1 years for females and 17.1 years for males. Thus, the completion of mandibular third molar eruption was found in both sexes before reaching the age of 18. In all individuals who had at least one tooth with completed eruption and who were younger than 17.4 years of age (n = 10), mineralization of the teeth in question was not complete. Based on our findings, the feature of assessing mandibular third molar eruption in PAN cannot be relied upon for determining age of majority.

Correlations between Dental Age, Skeletal Age, and Mandibular Morphologic Index Changes in Turkish Children in Eastern Anatolia and Their Chronological Age during the Pubertal Growth Spurt Period: A Cross-Sectional Study.

In age determination, different methods aiming to obtain the closest result to chronological age have been investigated so far. The most commonly used one among these is the radiological method, which is usually used to evaluate the developmental stages of wrist bones or teeth. In our study, we assessed bone age estimations using the Gilsanz-Ratib atlas (GRA), which has recently become commonly used for children aged 9 to 15 years; evaluated the dental age, determined with Cameriere's European method; conducted morphometric measurements of the mandibular bone; and then examined their relationships with chronological age. The results of our study reveal that, in children during the puberty growth spurt, Cameriere's EU formula might have higher accuracy in estimating chronological age in younger age groups, while the GRA might be more accurate for older ages. Additionally, we conclude that of the mandibular morphometric measurements, condylar height and tangential ramus height show strong positive correlations with age. As a result, we conclude that the morphometric measurements evaluated in the present study can be used as auxiliary methods in forensic anthropology and forensic dentistry.

Normative data for insulin-like growth factor-1 (IGF-1) in healthy children and adolescents from India.

BACKGROUND: Serum IGF-1 is an important biochemical tool to diagnose and monitor GH-related disorders. However, ethnic-specific Indian data following consensus criteria for the establishment of normative data, are not available. Our objective was to generate chronological age (CA)-, bone age (BA)- and Tanner stage-specific normative data for IGF-1 in healthy Indian children and adolescents. METHODS: A cross-sectional epidemiological study was conducted in schools and the community, which enrolled apparently healthy children and adolescents with robust exclusion criteria. The outcome measure was serum IGF-1 assessed using an electro-chemiluminescence immunoassay (ECLIA). The 2.5th, 5th, 10th, 25th, 50th (median), 75th, 90th, 95th, and 97.5th centiles for IGF-1 were estimated using generalized additive models. RESULTS: We recruited 2226 apparently healthy participants and following exclusion, 1948 (1006 boys, 942 girls) were included in the final analysis. Girls had median IGF-1 peak at CA of 13 years (321.7 ng/mL), BA of 14 years (350.2 ng/mL) and Tanner stage IV (345 ng/mL), while boys had median IGF-1 peak at CA of 15 years (318.9 ng/mL) BA of 15 years (340.6 ng/mL) and Tanner stage III (304.8 ng/mL). Girls had earlier rise, peak and higher IGF-1 values. The reference interval (2.5th-97.5th percentile) was broader during peri-pubertal ages, indicating a higher physiological variability. CONCLUSION: This study provides ethnicity-specific normative data on serum IGF-1 and will improve the diagnostic utility of IGF-1 in the evaluation and management of growth disorders in Indian children and adolescents.

A new method for vascular age estimation based on relative risk difference in vascular aging.

OBJECTIVE: The current models of estimating vascular age (VA) primarily rely on the regression label expressed with chronological age (CA), which does not account individual differences in vascular aging (IDVA) that are difficult to describe by CA. This may lead to inaccuracies in assessing the risk of cardiovascular disease based on VA. To address this limitation, this work aims to develop a new method for estimating VA by considering IDVA. This method will provide a more accurate assessment of cardiovascular disease risk. METHODS: Relative risk difference in vascular aging (RRDVA) is proposed to replace IDVA, which is represented as the numerical difference between individual predicted age (PA) and the corresponding mean PA of healthy population. RRDVA and CA are regard as the influence factors to acquire VA. In order to acquire PA of all samples, this work takes CA as the dependent variable, and mines the two most representative indicators from arteriosclerosis data as the independent variables, to establish a regression model for obtaining PA. RESULTS: The proposed VA based on RRDVA is significantly correlated with 27 indirect indicators for vascular aging evaluation. Moreover, VA is better than CA by comparing the correlation coefficients between VA, CA and 27 indirect indicators, and RRDVA greater than zero presents a higher risk of disease. CONCLUSION: The proposed VA overcomes the limitation of CA in characterizing IDVA, which may help young groups with high disease risk to promote healthy behaviors.

Biological age as estimated by baseline circulating metabolites is associated with incident diabetes and mortality.

OBJECTIVES: It is unclear how metabolomic assessment of biological aging performs in non-White populations and whether such an approach can predict future mortality. We aimed to evaluate the application of serum metabolomics combined with machine learning methodologies to predict incident diabetes and mortality in a Thai population. DESIGN, SETTING AND PARTICIPANTS: We analyzed serum samples and mortality data over 11 years from among 454 participants with no previous history of diabetes and with a fasting plasma glucose ≥85th percentile (5.4 mmol/L) but <7 mmol/L. MEASUREMENTS: Untargeted serum metabolomics were assessed using liquid chromatography/mass spectrometry. A deep artificial neural network was used to predict biological age based on serum metabolite profiles and chronological age. RESULTS: The mean age of participants was 40.5 ± 6.4 years, and 70.8% were men. We found a significant positive correlation between metabolomic age and chronological age (r = 0.71, P < 0.001). After 5 years, 61 of 404 participants with available glycated hemoglobin status (15.1%) progressed to diabetes. Chronological age was associated with incident diabetes but was not significant (P = 0.08), after adjusting for BMI and sex. Metabolomic age was significantly related to incident diabetes after controlling for BMI and sex (P < 0.05). Over the 11-year follow-up, 10 participants died owing to non-accidental causes. When metabolomic age and chronological age were included together in the model, metabolomic age (but not chronological age) was associated with mortality, independent of age, sex, and BMI. Among all identifiable metabolites, beta-D-mannosylphosphodecaprenyl and phosphatidylserines were the five leading metabolites associated with mortality. CONCLUSION: We concluded that serum metabolomic profile was associated with incident diabetes as well as mortality over our 11-year study period, which may render it potentially useful in assessing biological aging in humans.

Progress in the study of aging marker criteria in human populations.

The use of human aging markers, which are physiological, biochemical and molecular indicators of structural or functional degeneration associated with aging, is the fundamental basis of individualized aging assessments. Identifying methods for selecting markers has become a primary and vital aspect of aging research. However, there is no clear consensus or uniform principle on the criteria for screening aging markers. Therefore, we combine previous research from our center and summarize the criteria for screening aging markers in previous population studies, which are discussed in three aspects: functional perspective, operational implementation perspective and methodological perspective. Finally, an evaluation framework has been established, and the criteria are categorized into three levels based on their importance, which can help assess the extent to which a candidate biomarker may be feasible, valid, and useful for a specific use context.

Greulich and Pyle atlas: a non-reliable skeletal maturity assessment method in the North Indian population.

Forensic age assessments are crucial in the evaluation of criminal responsibility and preventing false age claims. Of all the methods available, the Greulich and Pyle (GP) atlas is most commonly used for age estimation purposes. Therefore, the current study sought to analyze the reliability and applicability of the GP standard and, additionally, to determine any possible association between the socioeconomic status (SES), food habits, and estimated skeletal maturity in the North Indian population. The study included 627 (334 males and 293 females) healthy children up to 19 years of age with varying SES and food habits. The skeletal age (SA) was estimated by three different evaluators using the GP atlas. The chronological mean age (CA) and SA were compared in different age cohorts. A paired t-test and a Pearson chi-square test were applied to show the difference between CA and estimated SA and the association of skeletal maturity with SES and food habits. The estimated skeletal age in males was retarded by 0.142 years or 1.72 months (p ≤ 0.05), whereas in females, it was retarded by 0.259 years or 3.12 months (p ≤ 0.05). In males, the GP method has significantly underestimated SA in age cohorts 3-4, 4-5, 6-7, 7-8, 8-9, and 12-13, whereas it overestimated in 10-11 and 18-19 years. However, in females, the SA was significantly underestimated in age groups 10-11, 12-13, and 14-15, respectively. Estimated skeletal maturity had no significant association with SES and food habits. The current study concludes that the GP atlas may not be applicable to North India's population. The observed difference in assessed skeletal maturity may be due to geographical region, genetics, hormonal effects, etc., which require further investigation. Hence, population-specific standards are necessary to determine the bone age of Indian children accurately.

Telomere length is not a useful tool for chronological age estimation in animals.

Telomeres are short repetitive DNA sequences capping the ends of chromosomes. Telomere shortening occurs during cell division and may be accelerated by oxidative damage or ameliorated by telomere maintenance mechanisms. Consequently, telomere length changes with age, which was recently confirmed in a large meta-analysis across vertebrates. However, based on the correlation between telomere length and age, it was concluded that telomere length can be used as a tool for chronological age estimation in animals. Correlation should not be confused with predictability, and the current data and studies suggest that telomeres cannot be used to reliably predict individual chronological age. There are biological reasons for why there is large individual variation in telomere dynamics, which is mainly due to high susceptibility to a wide range of environmental, but also genetic factors, rendering telomeres unfeasible as a tool for age estimation. The use of telomeres for chronological age estimation is largely a misguided effort, but its occasional reappearance in the literature raises concerns that it will mislead resources in wildlife conservation.

Predicting chronological age based on age-related osteophyte development in the superior and inferior vertebral centrum margins of T12-L5.

The purpose of this study was to determine the relationship between vertebral margins at individual vertebral levels between T12-L5 vertebra and chronological age and develop predictive models. Three hundred and nineteen CT scans from a medical imaging database in North America were randomly selected. Three superior and inferior vertebral margin sites were scored based on observable age-related changes. All individual vertebral margin site scores significantly correlated with age at death with Pearson r values ranging from 0.47 to 0.77. Totaling the individual vertebral margin site scores for L1-L5 improved Pearson r to 0.92. All resulting predictive models were significant, and the best models predicted age at death within 10 years 70%-76% of the time for males, females, and combined male and females. In conclusion, this study produced accurate and reliable models to predict age at death using age-related changes in the spine for a North American population.

Epigenetic age biomarkers and risk assessment in adult spinal deformity: a novel association of biological age with frailty and disability.

OBJECTIVE: Surgery for spinal deformity has the potential to improve pain, disability, function, self-image, and mental health. These surgical procedures carry significant risk and require careful selection, optimization, and risk assessment. Epigenetic clocks are age estimation tools derived by measuring the methylation patterns of specific DNA regions. The study of biological age in the adult deformity population has the potential to shed insight onto the molecular basis of frailty and to improve current risk assessment tools. METHODS: Adult patients who underwent deformity surgery were prospectively enrolled. Preoperative whole blood samples were used to assess epigenetic age and telomere length. DNA methylation patterns were quantified and processed to extract 4 principal component (PC)-based epigenetic age clocks (PC Horvath, PC Hannum, PC PhenoAge, and PC GrimAge) and the instantaneous pace of aging (DunedinPACE). Telomere length was assessed using both quantitative polymerase chain reaction (telomere to single gene [T/S] ratio) and a methylation-based telomere estimator (PC DNAmTL). Patient demographic and surgical data included age, BMI, American Society of Anesthesiologists Physical Status Classification System class, and scores on the Charlson Comorbidity Index, adult spinal deformity frailty index (ASD-FI), Edmonton Frail Scale (EFS), Oswestry Disability Index, and Scoliosis Research Society-22r questionnaire (SRS-22r). Medical or surgical complications within 90 days of surgery were collected. Spearman correlations and beta coefficients (ß) from linear regression, adjusted for BMI and sex, were calculated. RESULTS: Eighty-three patients were enrolled with a mean age of 65 years, and 45 were women (54%). All patients underwent posterior fusion with a mean of 11 levels fused and 33 (40%) 3-column osteotomies were performed. Among the epigenetic clocks adjusted for BMI and sex, DunedinPACE showed a significant association with ASD-FI (ß = 0.041, p = 0.002), EFS (ß = 0.696, p = 0.026), and SRS-22r (ß = 0.174, p = 0.013) scores. PC PhenoAge showed associations with ASD-FI (ß = 0.029, p = 0.028) and SRS-22r (ß = 0.159, p = 0.018) scores. PC GrimAge showed associations with ASD-FI (ß = 0.029, p = 0.037) and SRS-22r (ß = 0.161, p = 0.025) scores. Patients with postoperative complications were noted to have shorter telomere length (T/S 0.790 vs 0.858, p = 0.049), even when the analysis controlled for BMI and sex (OR = 1.71, 95% CI 1.07-2.87, p = 0.031). CONCLUSIONS: Epigenetic clocks showed significant associations with markers of frailty and disability, while patients with postoperative complications had shorter telomere length. These data suggest a potential role for aging biomarkers as components of surgical risk assessment. Integrating biological age into current risk calculators may improve their accuracy and provide valuable information for patients, surgeons, and payers.

The biological age model for evaluating the degree of aging in centenarians.

BACKGROUND: Biological age (BA) has been used to assess individuals' aging conditions. However, few studies have evaluated BA models' applicability in centenarians. METHODS: Important organ function examinations were performed in 1798 cases of the longevity population (80∼115 years old) in Hainan, China. Eighty indicators were selected that responded to nutritional status, cardiovascular function, liver and kidney function, bone metabolic function, endocrine system, hematological system, and immune system. BA models were constructed using multiple linear regression (MLR), principal component analysis (PCA), Klemera and Doubal method (KDM), random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and light gradient boosting machine (lightGBM) methods. A tenfold crossover validated the efficacy of models. RESULTS: A total of 1398 participants were enrolled, of whom centenarians accounted for 49.21%. Seven aging markers were obtained, including estimated glomerular filtration rate, albumin, pulse pressure, calf circumference, body surface area, fructosamine, and complement 4. Eight BA models were successfully constructed, namely MLR, PCA, KDM1, KDM2, RF, SVM, XGBoost and lightGBM, which had the worst R2 of 0.45 and the best R2 of 0.92. The best R2 for cross-validation was KDM2 (0.89), followed by PCA (0.62). CONCLUSION: In this study, we successfully applied eight methods, including traditional methods and machine learning, to construct models of biological age, and the performance varied among the models.