DNA Methylation Clocks in Aging: Categories, Causes, and Consequences.

Age-associated changes to the mammalian DNA methylome are well documented and thought to promote diseases of aging, such as cancer. Recent studies have identified collections of individual methylation sites whose aggregate methylation status measures chronological age, referred to as the DNA methylation clock. DNA methylation may also have value as a biomarker of healthy versus unhealthy aging and disease risk; in other words, a biological clock. Here we consider the relationship between the chronological and biological clocks, their underlying mechanisms, potential consequences, and their utility as biomarkers and as targets for intervention to promote healthy aging and longevity.

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.

Insights into dental age estimation: introducing multiple regression data from a Black South African population on modified gustafson's criteria.

Dental Age Estimation (DAE) is an effective instrument of the rule of law for verifying dubious age claims in living individuals. Once tooth development is complete, only degenerative dental characteristics can be used for this purpose. The influence of ethnicity on these degenerative dental characteristics has not been clarified.Degenerative changes were examined using modified Gustafson's criteria including secondary dentin formation, cementum apposition, periodontal recession and attrition using the Olze et al. (2012) staging scales. Orthopantomograms of 1882 black South Africans, consisting of 934 females and 948 males, from 12.00 to 40.96 years of chronological age were utilized. Two independent examiners performed the evaluations, with one of the two evaluating all radiographs twice.The relationship between individual characteristics and chronological age was analyzed using multiple regression analysis with chronological age as the dependent variable. The resulting R2 values ranged from 0.22 to 0.35, and the standard error of estimate were between 6.6 and 7.3 years. The correlation with age was consistently lower for females compared to males. The characteristic of cementum apposition emerged as critical in this population, due to a particularly low correlation with age and observer agreements partly in the "slight" range. The formula's values for the correlation with age were in general below the literature values for other populations. Overall, the limited precision of the age estimation by the formulae presented, especially for females, must be emphasized. The question of whether ethnicity per se exerts an influence on the characteristics in question, or whether the different socio-economic status, which encompasses factors such as nutrition and healthcare, is the determining factor, needs to be assessed in future studies.

Molecular age prediction using skull bone samples from individuals with and without signs of decomposition: a multivariate approach combining analysis of posttranslational protein modifications and DNA methylation.

The prediction of the chronological age of a deceased individual at time of death can provide important information in case of unidentified bodies. The methodological possibilities in these cases depend on the availability of tissues, whereby bones are preserved for a long time due to their mineralization under normal environmental conditions. Age-dependent changes in DNA methylation (DNAm) as well as the accumulation of pentosidine (Pen) and D-aspartic acid (D-Asp) could be useful molecular markers for age prediction. A combination of such molecular clocks into one age prediction model seems favorable to minimize inter- and intra-individual variation. We therefore developed (I) age prediction models based on the three molecular clocks, (II) examined the improvement of age prediction by combination, and (III) investigated if samples with signs of decomposition can also be examined using these three molecular clocks. Skull bone from deceased individuals was collected to obtain a training dataset (n = 86), and two independent test sets (without signs of decomposition: n = 44, with signs of decomposition: n = 48). DNAm of 6 CpG sites in ELOVL2, KLF14, PDE4C, RPA2, TRIM59 and ZYG11A was analyzed using massive parallel sequencing (MPS). The D-Asp and Pen contents were analyzed by high performance liquid chromatography (HPLC). Age prediction models based on ridge regression were developed resulting in mean absolute errors (MAEs)/root mean square errors (RMSE) of 5.5years /6.6 years (DNAm), 7.7 years /9.3 years (Pen) and 11.7 years /14.6 years (D-Asp) in the test set. Unsurprisingly, a general lower accuracy for the DNAm, D-Asp, and Pen models was observed in samples from decomposed bodies (MAE: 7.4-11.8 years, RMSE: 10.4-15.4 years). This reduced accuracy could be caused by multiple factors with different impact on each molecular clock. To acknowledge general changes due to decomposition, a pilot model for a possible age prediction based on the decomposed samples as training set improved the accuracy evaluated by leave-one-out-cross validation (MAE: 6.6-12 years, RMSE: 8.1-15.9 years). The combination of all three molecular age clocks did reveal comparable MAE and RMSE results to the pure analysis of the DNA methylation for the test set without signs of decomposition. However, an improvement by the combination of all three clocks was possible for the decomposed samples, reducing especially the deviation in case of outliers in samples with very high decomposition and low DNA content. The results demonstrate the general potential in a combined analysis of different molecular clocks in specific cases.

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.

The Gut and Skin Microbiome and Its Association with Aging Clocks.

Aging clocks are predictive models of biological age derived from age-related changes, such as epigenetic changes, blood biomarkers, and, more recently, the microbiome. Gut and skin microbiota regulate more than barrier and immune function. Recent studies have shown that human microbiomes may predict aging. In this narrative review, we aim to discuss how the gut and skin microbiomes influence aging clocks as well as clarify the distinction between chronological and biological age. A literature search was performed on PubMed/MEDLINE databases with the following keywords: "skin microbiome" OR "gut microbiome" AND "aging clock" OR "epigenetic". Gut and skin microbiomes may be utilized to create aging clocks based on taxonomy, biodiversity, and functionality. The top contributing microbiota or metabolic pathways in these aging clocks may influence aging clock predictions and biological age. Furthermore, gut and skin microbiota may directly and indirectly influence aging clocks through the regulation of clock genes and the production of metabolites that serve as substrates or enzymatic regulators. Microbiome-based aging clock models may have therapeutic potential. However, more research is needed to advance our understanding of the role of microbiota in aging clocks.

[The LittlEARS® Auditory Questionnaire : An analysis of multicentre data of children after early bilateral cochlear implant placement]. / Der LittlEARS® Hörfragebogen : Auswertung multizentrischer Daten von Kindern nach früher bilateraler Cochleaimplantatversorgung.

BACKGROUND: In order to optimise the support of children with cochlear implants (CI), it is very important to detect slow developmental processes as early as possible. Data from the LittlEARS® Auditory Questionnaire (LEAQ) from children with early bilateral CI are evaluated and presented in relation to age and hearing age and compared with language development data recorded later. MATERIALS AND METHODS: This retrospective multicentre study included data from a total of 554 children for whom at least one LEAQ was completed during the course of CI rehabilitation. Children without additional disabilities who received bilateral simultaneous or sequential CI treatment were included. RESULTS: As expected, there are high correlations between hearing age (HA) and the overall LEAQ total score. When analysed according to chronological age (CA), development runs roughly parallel to the development of children with normal hearing, albeit at a lower level. Children implanted early up to an age of ≤ 12 months consistently achieve approximately 7-8 raw points more. Only the LEAQ results of the later test times (from the age of 18 months) correlate with some areas of the speech development test for children (SETK; areas 3-5). CONCLUSION: The earliest possible detection of critical developmental processes in children with CI is extremely important. In the case of very early CI fitting, the CA should be used as a reference measure in diagnostics. The LEAQ values determined for the group of children with CI are suitable to a limited extent as generally valid reference values for children with early bilateral CI. Further studies should continue to work out the correlations between early preverbal development and later speech development.

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.

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.

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.

Association of Retinal Age Gap and Risk of Kidney Failure: A UK Biobank Study.

RATIONALE & OBJECTIVE: The incidence of kidney failure is known to increase with age. We have previously developed and validated the use of retinal age based on fundus images as a biomarker of aging. However, the association of retinal age with kidney failure is not clear. We investigated the association of retinal age gap (the difference between retinal age and chronological age) with future risk of kidney failure. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 11,052 UK Biobank study participants without any reported disease for characterizing retinal age in a deep learning algorithm. 35,864 other participants with retinal images and no kidney failure were followed to assess the association between retinal age gap and the risk of kidney failure. EXPOSURE: Retinal age gap, defined as the difference between model-based retinal age and chronological age. OUTCOME: Incident kidney failure. ANALYTICAL APPROACH: A deep learning prediction model used to characterize retinal age based on retinal images and chronological age, and Cox proportional hazards regression models to investigate the association of retinal age gap with incident kidney failure. RESULTS: After a median follow-up period of 11 (IQR, 10.89-11.14) years, 115 (0.32%) participants were diagnosed with incident kidney failure. Each 1-year greater retinal age gap at baseline was independently associated with a 10% increase in the risk of incident kidney failure (HR, 1.10 [95% CI, 1.03-1.17]; P=0.003). Participants with retinal age gaps in the fourth (highest) quartile had a significantly higher risk of incident kidney failure compared with those in the first quartile (HR, 2.77 [95% CI, 1.29-5.93]; P=0.009). LIMITATIONS: Limited generalizability related to the composition of participants in the UK Biobank study. CONCLUSIONS: Retinal age gap was significantly associated with incident kidney failure and may be a promising noninvasive predictive biomarker for incident kidney failure.

Retinal microvascular complexity as a putative biomarker of biological age: a pilot study.

Physiological changes associated with aging increase the risk for the development of age-related diseases. This increase is non-specific to the type of age-related disease, although each disease develops through a unique pathophysiologic mechanism. People who age at a faster rate develop age-related diseases earlier in their life. They have an older "biological age" compared to their "chronological age". Early detection of individuals with accelerated aging would allow timely intervention to postpone the onset of age-related diseases. This would increase their life expectancy and their length of good quality life. The goal of this study was to investigate whether retinal microvascular complexity could be used as a biomarker of biological age. Retinal images of 68 participants ages ranging from 19 to 82 years were collected in an observational cross-sectional study. Twenty of the old participants had age-related diseases such as hypertension, type 2 diabetes, and/or Alzheimer's dementia. The rest of the participants were healthy. Retinal images were captured by a hand-held, non-mydriatic fundus camera and quantification of the microvascular complexity was performed by using Sholl's, box-counting fractal, and lacunarity analysis. In the healthy subjects, increasing chronological age was associated with lower retinal microvascular complexity measured by Sholl's analysis. Decreased box-counting fractal dimension was present in old patients, and this decrease was 2.1 times faster in participants who had age-related diseases (p = 0.047). Retinal microvascular complexity could be a promising new biomarker of biological age. The data from this study is the first of this kind collected in Montenegro. It is freely available for use.

A systematic overview of dental methods for age assessment in living individuals: from traditional to artificial intelligence-based approaches.

Dental radiographies have been used for many decades for estimating the chronological age, with a view to forensic identification, migration flow control, or assessment of dental development, among others. This study aims to analyse the current application of chronological age estimation methods from dental X-ray images in the last 6 years, involving a search for works in the Scopus and PubMed databases. Exclusion criteria were applied to discard off-topic studies and experiments which are not compliant with a minimum quality standard. The studies were grouped according to the applied methodology, the estimation target, and the age cohort used to evaluate the estimation performance. A set of performance metrics was used to ensure good comparability between the different proposed methodologies. A total of 613 unique studies were retrieved, of which 286 were selected according to the inclusion criteria. Notable tendencies to overestimation and underestimation were observed in some manual approaches for numeric age estimation, being especially notable in the case of Demirjian (overestimation) and Cameriere (underestimation). On the other hand, the automatic approaches based on deep learning techniques are scarcer, with only 17 studies published in this regard, but they showed a more balanced behaviour, with no tendency to overestimation or underestimation. From the analysis of the results, it can be concluded that traditional methods have been evaluated in a wide variety of population samples, ensuring good applicability in different ethnicities. On the other hand, fully automated methods were a turning point in terms of performance, cost, and adaptability to new populations.

Age estimation of children based on open apex measurement in the developing permanent dentition: an Egyptian formula.

BACKGROUND: Cameriere's original formula based on open apex measurements is a reliable, clinically applicable method for dental age estimation in different populations children. Dental development may differ between Egyptian children and other ethnic populations which may affect dental age accuracy using Cameriere's formula. AIM: Firstly, to verify Cameriere's original formula on large Egyptian children sample, secondly, to develop an Egyptian-specific formula based on Cameriere's method. MATERIAL AND METHODS: A prospective cross-sectional study of 762 good quality Orthopantomograms (OPGs) of 5-15 aged healthy Egyptian children selected from Nile Delta governorates between August 2020 and December 2021. Chronological age (CA) was calculated by subtracting birth date from radiograph date. OPGs were analyzed for N0, S, Xi morphologic variables using Sidexis program after that dental age was calculated using Cameriere's formula then compared to CA. Multiple linear regression model was used to adapt Cameriere's formula to construct an Egyptian formula. The same sample was used to verify the new formula accuracy. RESULTS: A total of 1093 OPGs were collected; 762 OPGs which met inclusion criteria were analyzed. Cameriere's original formula revealed - 0.59- and - 0.53-year underestimation of females and males dental age (DA) respectively (p < 0.001). Regression analysis using the morphologic variables showed that X4, X7, N0 contributed significantly to CA yielding Egyptian-specific formula. New formula showed - 0.12-year male underestimation and 0.1-year female overestimation (p > 0.05). CONCLUSION: Egyptian formula was more accurate than Cameriere's formula in Egyptian children. CLINICAL RELEVANCE: Egyptian-specific formula decreases the gap between CA and DA, so a relative approximate age is obtained that helps proper diagnosis and treatment planning for orthodontic and pediatric dentistry problems.

The Effects of Chronological Age on the Chondrogenic Potential of Mesenchymal Stromal Cells: A Systematic Review.

Tissue engineering and cell therapy for regenerative medicine have great potential to treat chronic disorders. In musculoskeletal disorders, mesenchymal stromal cells (MSCs) have been identified as a relevant cell type in cell and regenerative strategies due to their multi-lineage potential, although this is likely to be a result of their trophic and immunomodulatory effects on other cells. This PRISMA systematic review aims to assess whether the age of the patient influences the chondrogenic potential of MSCs in regenerative therapy. We identified a total of 3027 studies after performing a search of four databases, including Cochrane, Web of Science, Medline, and PubMed. After applying inclusion and exclusion criteria, a total of 14 papers were identified that were reviewed, assessed, and reported. Cell surface characterization and proliferation, as well as the osteogenic, adipogenic, and chondrogenic differentiation, were investigated as part of the analysis of these studies. Most included studies suggest a clear link between aged donor MSCs and diminished clonogenic and proliferative potential. Our study reveals a heterogeneous and conflicting range of outcomes concerning the chondrogenic, osteogenic, and adipogenic potential of MSCs in relation to age. Further investigations on the in vitro effects of chronological age on the chondrogenic potential of MSCs should follow the outcomes of this systematic review, shedding more light on this complex relationship.

DNA Methylation and Telomeres-Their Impact on the Occurrence of Atrial Fibrillation during Cardiac Aging.

Atrial fibrillation (AF) is the most common arrhythmia in humans. AF is characterized by irregular and increased atrial muscle activation. This high-frequency activation obliterates the synchronous work of the atria and ventricles, reducing myocardial performance, which can lead to severe heart failure or stroke. The risk of developing atrial fibrillation depends largely on the patient's history. Cardiovascular diseases are considered aging-related pathologies; therefore, deciphering the role of telomeres and DNA methylation (mDNA), two hallmarks of aging, is likely to contribute to a better understanding and prophylaxis of AF. In honor of Prof. Elizabeth Blackburn's 75th birthday, we dedicate this review to the discovery of telomeres and her contribution to research on aging.

Chronological Age and DNA Damage Accumulation in Blood Mononuclear Cells: A Linear Association in Healthy Humans after 50 Years of Age.

Aging is characterized by the progressive deregulation of homeostatic mechanisms causing the accumulation of macromolecular damage, including DNA damage, progressive decline in organ function and chronic diseases. Since several features of the aging phenotype are closely related to defects in the DNA damage response (DDR) network, we have herein investigated the relationship between chronological age and DDR signals in peripheral blood mononuclear cells (PBMCs) from healthy individuals. DDR-associated parameters, including endogenous DNA damage (single-strand breaks and double-strand breaks (DSBs) measured by the alkaline comet assay (Olive Tail Moment (OTM); DSBs-only by γH2AX immunofluorescence staining), DSBs repair capacity, oxidative stress, and apurinic/apyrimidinic sites were evaluated in PBMCs of 243 individuals aged 18-75 years, free of any major comorbidity. While OTM values showed marginal correlation with age until 50 years (rs = 0.41, p = 0.11), a linear relationship was observed after 50 years (r = 0.95, p < 0.001). Moreover, individuals older than 50 years showed increased endogenous DSBs levels (γH2Ax), higher oxidative stress, augmented apurinic/apyrimidinic sites and decreased DSBs repair capacity than those with age lower than 50 years (all p < 0.001). Results were reproduced when we examined men and women separately. Prospective studies confirming the value of DNA damage accumulation as a biomarker of aging, as well as the presence of a relevant agethreshold, are warranted.

Assessment of permanent teeth development in children with multiple persistent primary teeth.

BACKGROUND: Persistent primary teeth (PPT) may occur due to various local factors, or it may develop due to general factors such as systemic diseases and syndromes. Since eruption and dental development are two different processes, it is important to investigate both processes to determine the actual cause of delayed tooth eruption. The study aimed to evaluate the dental development of a group of Turkish children with multiple PPT using the Willems dental age estimation method. STUDY DESIGN: Digital panoramic radiographs of children and adolescents aged between 9 and 15 years were retrieved, assessed and categorized. A total of 80 radiographs of patients with more than one PPT were selected and matched with children without PPT. Dental age was calculated using the method of Willems et al. All analyses were conducted using the SPSS statistical software. The statistical significance was set at 0.05. RESULTS: The permanent tooth development of children with multiple PPT could be delayed by 0.5-4 years compared to healthy ones. A strong positive correlation was found between the number of PPT and deviation for both females and males (p < 0.001). CONCLUSION: In conclusion, we found that permanent tooth development of children with multiple PPT could be delayed compared to healthy ones. In addition, as the number of PPT increased, the difference between chronological age and dental age also increased, especially in males.

DENSEN: a convolutional neural network for estimating chronological ages from panoramic radiographs.

BACKGROUND: Age estimation from panoramic radiographs is a fundamental task in forensic sciences. Previous age assessment studies mainly focused on juvenile rather than elderly populations (> 25 years old). Most proposed studies were statistical or scoring-based, requiring wet-lab experiments and professional skills, and suffering from low reliability. RESULT: Based on Soft Stagewise Regression Network (SSR-Net), we developed DENSEN to estimate the chronological age for both juvenile and older adults, based on their orthopantomograms (OPTs, also known as orthopantomographs, pantomograms, or panoramic radiographs). We collected 1903 clinical panoramic radiographs of individuals between 3 and 85 years old to train and validate the model. We evaluated the model by the mean absolute error (MAE) between the estimated age and ground truth. For different age groups, 3-11 (children), 12-18 (teens), 19-25 (young adults), and 25+ (adults), DENSEN produced MAEs as 0.6885, 0.7615, 1.3502, and 2.8770, respectively. Our results imply that the model works in situations where genders are unknown. Moreover, DENSEN has lower errors for the adult group (> 25 years) than other methods. The proposed model is memory compact, consuming about 1.0 MB of memory overhead. CONCLUSIONS: We introduced a novel deep learning approach DENSEN to estimate a subject's age from a panoramic radiograph for the first time. Our approach required less laboratory work compared with existing methods. The package we developed is an open-source tool and applies to all different age groups.

Older Patients with Lung Cancer: a Summary of Seminal Contributions to Optimal Patient Care.

PURPOSE OF REVIEW: This review aspires to summarize the landmark advancements in the management of the non-small cell lung cancer (NSCLC), both historically and contemporarily with special focus in older adults. RECENT FINDINGS: The past two decades have witnessed remarkable improvements in the diagnosis and management of lung cancer. Screening recommendations now facilitate earlier diagnosis in high-risk individuals, PET/CT scans have improved radiologic accuracy in identifying sites of disease, and surgical management with minimally invasive techniques has rendered surgery safer in those with limited physiologic reserve. Radiation enhancements, especially radiosurgery, have extended the reach and safety of radiation among high-risk populations. Finally, the revolution in precision medicine with identification of numerous actionable mutations, the advent of immunotherapy, and enhanced supportive care have revolutionized the outcomes in patients with advanced lung cancer. Older adults who represent a majority of patients battling lung cancer have not benefitted to the same extent as their younger counterparts. This special population is only expected to grow in coming days. Hence, addressing major gaps in the management of older adults with NSCLC and optimizing the care are much needed.