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.

Content and distribution of cyanogenic compounds in cassava roots and leaves in association with physiological age.

BACKGROUND: Cassava roots are widely consumed in tropical regions of Asia, Africa, and Latin America. Although the protein, vitamin, carotenoid, and mineral content in the leaves makes them a nutritionally attractive option, their consumption is limited due to their high levels of cyanogenic compounds (CCs). In this study, the CC content in different parts of the plant (leaves, storage root cortex, and parenchyma) was assessed at harvest for 50 landrace genotypes representative of cassava diversity in Latin America. The changes in CC in leaves at different physiological ages (3, 6, 9, and 11 months after planting) were also investigated. RESULTS: The average CC was higher in the cortex (804 ppm) and leaves (655 ppm) than in root parenchyma (305 ppm). Genotypes from different regions of Latin America, as identified by seven genetic diversity groups, differed significantly in CC levels. The Andean and Amazon groups had, respectively, the lowest (P = 0.0008) and highest (P < 0.0001) CC levels in all three parts of the plants. Cyanogenic compound concentrations were higher in leaves from young plants (P < 0.0001) and decreased with increasing physiological age. CONCLUSION: The results help to guide the selection of parental lines with low CC levels for breeding and to contribute to the expanded use of cassava and its by-products for food and feed. Cassava for fresh consumption, especially, requires varieties with low total CC content, especially in the root cortex and parenchyma. COL1108 (204, 213, and 174 ppm, respectively, in the parenchyma, cortex, and leaves) and PER297 (83, 238, and 299 ppm, respectively, in the parenchyma, cortex, and leaves) can fulfill this requirement. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Seasonal Dynamics and Physiological Age of Ixodid Ticks Collected from Dogs.

In order to reproduce and complete life cycles, ticks have to feed on different hosts, thus participating as vectors and reservoirs in the maintenance and circulation of different pathogens. Since dogs can serve as suitable hosts for numerous tick species, the aims of this study were to determine tick species and their seasonal occurrence on pet dogs and to compare the accuracy of three indices frequently used to calculate engorged female physiological age. Ticks were collected from dogs brought to veterinary clinics. Three indices were analyzed: scutal index, alloscutal/scutal index ratio, and physiological age index. Four tick species were identified: Ixodes ricinus, Dermacentor marginatus, D. reticulatus, and Rhipicephalus sanguineus group, and the last was the most abundant. The highest number of collected ticks was in April, but two species were continuously active throughout the year. The statistical analyses distinguished the physiological age index as more precise because of lower variability. Dog owners usually ignore regular dog anti-tick treatments throughout the year, as they are not aware that ticks could be active during the winter months. Tick surveillance is unquestionably important in order to monitor and prevent the distribution of these vectors and also the diseases they transmit.

Temperature-dependent development of Helicoverpa armigera (Lepidoptera: Noctuidae) at constant temperatures: instar pathways and stage transition models with semifield validation.

Temperature-dependent development of Helicoverpa armigera (Hüber) fed with an artificial diet was studied at different temperatures. The instar pathway (IPW) defined as the number of instars prior to pupation significantly affected larval development time, with higher IPW leading to longer larval development time. The IPW was determined at the fifth instar to proceed to 6-7 IPW, when the development time of fifth instar was largely shortened. Accordingly, the development time after the fourth instar was combined (i.e., the fifth-seventh instar) as a single stage to simplify the various IPW and applied to develop phenology models. In linear models, the lower threshold temperature (LT) and thermal constant (degree-days, DD) for each stage were estimated. DD based on the common LT of 10.7 °C were 43, 287, and 191 DD for eggs, larvae, and pupae, respectively. DD model (253.6 DD with LT 10.3 °C for larvae and 181.5 DD with 11.6 °C for pupae) showed good performance in predicting the 50% occurrences of pupae and adults. In nonlinear models, stage transition (ST) models were constructed using the development rate and distribution models to simulate the proportion of individuals shifted from one stage to the next stage. The ST model showed good performance, indicating an average discrepancy of 1.74 days at 25%, 50%, 75%, and 90% adult emergence. Our models developed here will be useful to predict the phenology of H. armigera in the field and to construct a deterministic population model in the future.

Explainable machine learning framework to predict personalized physiological aging.

Attaining personalized healthy aging requires accurate monitoring of physiological changes and identifying subclinical markers that predict accelerated or delayed aging. Classic biostatistical methods most rely on supervised variables to estimate physiological aging and do not capture the full complexity of inter-parameter interactions. Machine learning (ML) is promising, but its black box nature eludes direct understanding, substantially limiting physician confidence and clinical usage. Using a broad population dataset from the National Health and Nutrition Examination Survey (NHANES) study including routine biological variables and after selection of XGBoost as the most appropriate algorithm, we created an innovative explainable ML framework to determine a Personalized physiological age (PPA). PPA predicted both chronic disease and mortality independently of chronological age. Twenty-six variables were sufficient to predict PPA. Using SHapley Additive exPlanations (SHAP), we implemented a precise quantitative associated metric for each variable explaining physiological (i.e., accelerated or delayed) deviations from age-specific normative data. Among the variables, glycated hemoglobin (HbA1c) displays a major relative weight in the estimation of PPA. Finally, clustering profiles of identical contextualized explanations reveal different aging trajectories opening opportunities to specific clinical follow-up. These data show that PPA is a robust, quantitative and explainable ML-based metric that monitors personalized health status. Our approach also provides a complete framework applicable to different datasets or variables, allowing precision physiological age estimation.

What do we mean by "aging"? Questions and perspectives revealed by studies in Drosophila.

What is the nature of aging, and how best can we study it? Here, using a series of questions that highlight differing perspectives about the nature of aging, we ask how data from Drosophila melanogaster at the organismal, tissue, cellular, and molecular levels shed light on the complex interactions among the phenotypes associated with aging. Should aging be viewed as an individual's increasing probability of mortality over time or as a progression of physiological states? Are all age-correlated changes in physiology detrimental to vigor or are some compensatory changes that maintain vigor? Why do different age-correlated functions seem to change at different rates in a single individual as it ages? Should aging be considered as a single, integrated process across the scales of biological resolution, from organismal to molecular, or must we consider each level of biological scale as a separate, distinct entity? Viewing aging from these differing perspectives yields distinct but complementary interpretations about the properties and mechanisms of aging and may offer a path through the complexities related to understanding the nature of aging.

Multiple physiological cohorts comprise seasonal activity of wild Amblyomma americanum (Acari: Ixodidae) nymphs.

Nymphs of the hard tick Amblyomma americanum (L.) are an important life stage in the maintenance and transmission of tick-borne pathogens. As pathogen composition can vary across developmental cohorts, it is essential to understand the demographic structure of the questing population. Amblyomma americanum nymphs often display a second peak in activity during late summer, but it is unknown whether this peak represents older overwintered ticks or younger newly molted ticks. The objective of this study was to examine the heme concentration in field-captured A. americanum nymphs to determine if the questing population consists of one physiological cohort or multiple cohorts in a season. Ticks were collected from March to August in an old field of primarily non-native grasses, and heme concentration was used to assess physiological age. LOESS modeling depicted that heme concentration in the population declined from March to early July but increased in later sampling sessions. As ticks cannot replenish declining heme stores without a blood meal, a late-summer spike in heme concentration demonstrates that newly molted nymphs are entering the active population. The vector potential of these newly emerging nymphs may differ from those collected earlier in the year as pathogen diversity depends on reservoir host dynamics and timing of larval feeding.

Where Are Populations Aging Better? A Global Comparison of Healthy Aging Across Organization for Economic Cooperation and Development Countries.

OBJECTIVES: Global comparisons and large samples are needed to inform policy makers about aging trends among people aged older than 60 years. Using harmonized data gathered from the Gateway to Global Aging data, we introduce a new framework to measure healthy aging across 13 OECD countries. METHODS: First, we developed an original measure of physiological age (PA), that is, a measure of age weighted for the influence of frailty, activities of daily living limitations, and comorbidities. Second, we compared healthy aging measures across 13 countries based on a ranking of the countries according to the discrepancy between estimated PA and chronological age (CA). Third, we explored the socioeconomic factors associated with healthy aging. RESULTS: We found a strong correlation between our PA measure and biological age. Italy, Israel, and the United States are the 3 countries where PA is the highest (independent of CA), thus indicating aging in poor health. In contrast, Switzerland, The Netherlands, Greece, Sweden, and Denmark have much lower PA than CA, thus indicating healthy aging. Finally, the PA-CA discrepancy is higher among poorer, less educated, and single older individuals. CONCLUSIONS: Countries with higher PA need to implement or reinforce healthy aging measures and target the disadvantaged populations.

Seasonal changes in questing efficiency of wild Amblyomma americanum (Acari: Ixodidae) nymphs.

Understanding the factors which influence host-seeking behavior of ticks is essential to determine the risk they pose as a vector of pathogens. While many studies have evaluated the impact of environmental variables on tick behavior, few have examined how seasonal changes in physiological status may further modify patterns of activity. In this study, we measured differences in questing behavior of mid spring- and early summer-caught Amblyomma americanum nymphs held under standardized laboratory conditions. As both groups represent the same cohort of overwintered nymphs, we hypothesized that age-related changes in the older summer ticks may influence questing behavior. In each season, we collected nymphs from field and forest habitats in northeast Missouri, after which we placed each nymph individually in a desiccating vertical questing apparatus with a hydrating microenvironment at the base. On the day following collection, we recorded the height of each nymph in the apparatus bi-hourly from 04:00 to 22:00 and calculated the vertical displacement between consecutive observations. Despite displaying no differences in mean questing height throughout the experiment, active ticks collected in the summer group (n = 89) travelled greater cumulative distances between desiccating and hydrating microenvironments than those collected in the spring (n = 119). This suggests that questing efficiency decreases in summer nymphs to accommodate increased time allocation towards rehydration. While we observed no direct association between body size and distance travelled, body size of the nymphal population also decreased significantly from spring to summer. Overall, our results demonstrate that there are seasonal changes in how A. americanum responds to environmental conditions. To more accurately predict host-seeking behavior of ticks across seasons, models should incorporate physiological parameters of the active ticks in a given population.

Histological technique to detect the physiological age of the malaria vector mosquito Anopheles pharoensis (Diptera: Culicidae).

The risk of malaria recurrence increases due to the main vector, Anopheles pharoensis. The physiological age of the mosquito population is needed to expect malaria vector dynamics. The number of completed gonotrophic cycles is of great importance in determining the physiological age of females. A technique has been described that focuses on the number of dilatations remaining in the ovarioles after each oviposition to determine how many blood meals have been taken. At each gonotrophic cycle, the chances of infection of the vectors are repeated. The histological changes that occur immediately in the ovarioles and ovulation itself were studied. Under the influence of the contractions of the ovarian muscles, the eggs begin to move over the distal end of the ovariole into the inner oviduct. The terminal pedicle is markedly dilated near the diameter of the eggs. After the expulsion of the mature eggs, ovariole dilations were found at the point of their development in the terminal pedicle due to the accumulation of nurse cell remnants and follicular epithelium. The results were used to develop epidemiological localization and to evaluate the effectiveness of antimalaria interventions. The ovarian inspection often provides a technique to distinguish nulliparous from parous female anophelines. In addition, this study can provide basic entomological knowledge on the physiological age of mosquitoes by considering the histological changes in the ovaries, which allow the evaluation of vector management strategies in the field.

Vascular Aging Detected by Peripheral Endothelial Dysfunction Is Associated With ECG-Derived Physiological Aging.

Background An artificial intelligence algorithm that detects age using the 12-lead ECG has been suggested to signal "physiologic age." This study aimed to investigate the association of peripheral microvascular endothelial function (PMEF) as an index of vascular aging, with accelerated physiologic aging gauged by ECG-derived artificial intelligence-estimated age. Methods and Results This study included 531 patients who underwent ECG and a noninvasive PMEF assessment using reactive hyperemia peripheral arterial tonometry. Abnormal PMEF was defined as reactive hyperemia peripheral arterial tonometry index ≤2.0. Accelerated or delayed physiologic aging was calculated by the Δ age (ECG-derived artificial intelligence-estimated age minus chronological age), and the association between Δ age and PMEF as well as its impact on composite major adverse cardiovascular events were investigated. Δ age was higher in patients with abnormal PMEF than in patients with normal PMEF (2.3±7.8 versus 0.5±7.7 years; P=0.01). Reactive hyperemia peripheral arterial tonometry index was negatively associated with Δ age after adjustment for cardiovascular risk factors (standardized ß coefficient, -0.08; P=0.048). The highest quartile of Δ age was associated with an increased risk of major adverse cardiovascular events compared with the first quartile of Δ age in patients with abnormal PMEF, even after adjustment for cardiovascular risk factors (hazard ratio, 4.72; 95% CI, 1.24-17.91; P=0.02). Conclusions Vascular aging detected by endothelial function is associated with accelerated physiologic aging, as assessed by the artificial intelligence-ECG Δ age. Patients with endothelial dysfunction and the highest quartile of accelerated physiologic aging have a marked increase in risk for cardiovascular events.

Assessment of physiological age and antioxidant status of new somatic hybrid potato seeds during extended cold storage.

Yield components of potato are largely affected by the physiology age of the tuber seeds at planting. The current study focuses on monitoring seed tuber aging in two CN1 and CN2 somatic hybrid lines and Spunta (Sp) variety during 270 days of storage at 4 °C. Aging rate was monitored based on sprouting, emergence and tissue oxidation rates. Investigation of sprouting parameters such as physiological age index (PAI) considering physiological and chronological age and the incubation period (IP) indicated lower physiological age in hybrids than in Sp during the storage. Moreover, these analyses showed that off-seasonal growing conditions increased the aging, more clearly, in Sp tubers than in hybrid ones. However, dormancy periods (endodormancy and after storage dormancy) were equivalent in the different tuber lots. PAI and IP data when combined with those from emergence parameters (duration until emergence and stem number) seem more efficient for the characterization of the different potato lines. However, emergence indicators, when considered separately, were not able to distinguish clearly between seasonal and off-seasonal tubers. Data suggest that hybrid seeds exhibited high performances since they produced higher stem number per plant than Sp. The high aging rate in Sp tubers seems to be associated with the few developed stems. Biochemical analyses supported in part morphophysiological differences between hybrids and Sp seeds although these indicators seem more sensitive to aging. Indeed data showed that the dormancy break, and then, the development were associated with some level of tissue oxidation. Antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and carotenoids seem more enhanced after the release of dormancy. However, induction of these activities started earlier in off-seasonal tubers than in seasonal ones, this was consistent with their advanced aging level revealed by PAI and IP data. Activation of these antioxidants appears to respond effectively to the increase of ROS suggesting a better control of postharvest development and tissue deterioration especially in CN2 off-seasonal tubers. This study suggests that CN2 followed by CN1 exhibited the best performance compared to Sp variety.

Treatment decision-making in chronic lymphocytic leukaemia: Key factors for healthcare professionals. PRELIC study.

OBJECTIVE: To explore the preferences of Spanish healthcare professionals (haematologists and hospital pharmacists) for the treatment selection of active Chronic Lymphocytic Leukaemia (CLL) patients at first relapse, condition that mainly afflicts older adults. METHODS: A discrete choice experiment (DCE) was conducted among haematologists and hospital pharmacists. A literature review and a focus group informed the DCE design. CLL treatment settings were defined by seven attributes: four patient/disease-related attributes (age, functional status, comorbidities, and risk of the disease) and three treatment-related attributes (efficacy [hazard ratio of progression-free survival, HR-PFS], rate of discontinuations due to adverse events and cost). A mixed-logit model was used to determine choice-based preferences. Relative importance (RI) of attributes was calculated and compared between stakeholders. Willingness-to-pay (WTP) was estimated through the DCE. Besides, nine ad-hoc questions were posed, to explore more in depth CLL treatment decision making. RESULTS: A total of 130 participants (72 haematologists and 58 hospital pharmacists) answered the DCE. All attributes were significant predictors of preferences (p < 0.05) in the multinomial model. Higher RI was obtained for treatment-related attributes: the highest rated being 'cost' (23.8%) followed by 'efficacy' (20.9%). Regarding patient-related attributes, the highest RI was obtained for 'age' (18.1%). No significant differences (p > 0.05) in RI between haematologists and pharmacists were found. WTP for the treatment was higher for younger CLL patients. Ad-hoc questions showed that patient age and functional status influence treatment decisions. CONCLUSIONS: For healthcare professionals, 'cost' and 'efficacy' (treatment-related attributes) and age (patient-related attribute) are the main factors that determine CLL treatment selection at first relapse. WTP decreases as patient's age increases.

The influence of aging on the spatial and temporal variables of gait during usual and fast speeds in older adults aged 60 to 102 years.

BACKGROUND: With increases in life expectancy, it is important to understand the influence of aging on gait, given that this activity is related to the independence of older adults and may help in the development of health strategies that encourage successful aging in all phases of this process. RESEARCH QUESTION: To compare gait parameters with usual and fast speeds for independent and autonomous older adults throughout the aging process (60 to 102 years old), and also to identify which of the gait variables are best for identifying differences across the different age groups. METHODS: Two hundred older adults aged between 60 and 102 years were evaluated. The sample was divided into 3 age groups: 60 to 79 years, 80 to 89 years and 90 years and over. The analyzed gait variables were: speed (meters/s), cadence (steps/min), stride time (seconds), step length (centimeters), double support (percentage of the gait cycle), swing (percentage of the gait cycle), step length variability (CoV%) and stride time variability (CoV%). RESULTS: Group comparison regarding usual gait and fast gait revealed a significant difference in all gait variables. In addition, it can be seen that variables such as gait speed and step length showed greater effect sizes in intergroup comparison (usual gait: 0.48 and 0.47; fast gait: 0.36 and 0.40; respectively), possibly showing that these variables can better detect the changes observed with increasing age. CONCLUSION: There are differences in the gait performance of older adults from different age groups for usual and fast gait speeds, which is more evident regarding gait speed and step length variables. We recommend the use of usual gait for the identification of the effects of aging because, besides showing a higher effect size values it is more comfortable and requires less effort from older subjects.

Liver transplantation in Mexican older adults: A comparative single-center study. / Trasplante de hígado en adultos mayores mexicanos: un estudio comparativo en un solo centro.

INTRODUCTION: Liver disease is currently one of the leading causes of death in older adults and the only option deemed curative is liver transplantation. However, it is uncertain whether the successful results obtained in older adults that receive a liver transplant in developed countries can be replicated in developing countries. AIM: To determine if there are differences in the survival time between older (≥60years) and younger adults that underwent liver transplantation at a university-affiliated tertiary care center in Mexico City. MATERIALS AND METHODS: A 2-year longitudinal study was conducted. It included 244 participants that were divided into 2groups according to age at the time of transplantation: older adults (≥60years) and younger adults (18-59years). Survival time was defined as the number of days that elapsed between transplantation and death. Survival was expressed as Kaplan-Meier curves. RESULTS: Median age in the older adults (n=52) was 63.0 (IQR=60-69) and 23 participants were females (44.2%). In the younger adults (n=196) median age was 47.0 (IQR=16-59) and 104 were females (52%). The leading indication for transplant was hepatitisC virus. After the follow-up, fifteen participants died (12 younger adults and 3 older adults). No significant differences were observed between older and younger participants in postoperative complications, the number of re-admissions, or mean post-transplantation survival time. CONCLUSIONS: There were no statistically significant differences in relation to survival times between older and younger adults that received a liver transplant. Older patients in developing countries should not be excluded from the selection process due only to age.

The effects of age and dietary resistant starch on digestibility, fermentation end products in faeces and postprandial glucose and insulin responses of dogs.

The same food formulation processed to obtain two different starch gelatinisations (SG) and resistant starch (RS) contents was evaluated in old and adult dogs, regarding apparent total tract digestibility (ATTD) of nutrients, fermentation products in faeces, and postprandial glucose and insulin responses. A diet with corn was ground and extruded in two different ways, obtaining Low RS (2.2 g/kg DM; 99.9% of SG) and High RS (15.3 g/kg DM; 62.6% of SG). Each diet was fed to adults (4.0 ± 0.7 years) or old beagle dogs (11.5 ± 0.4 years) in a 2 (ages) x 2 (RS amounts) factorial arrangement with 8 dogs per food. Data were evaluated by analysis of variance, and postprandial responses by analysis of variance of repeated measurements over time (p < 0.05). Diet × age interaction was observed for protein ATTD, with lower values for old dogs fed High RS than those for the other treatments (p < 0.05). No age or diet effect was verified for the ATTD of other nutrients and faecal score. Faecal moisture and pH were higher for adults than that for old dogs (p < 0.05). The High RS food increased acetate, propionate and butyrate concentrations in faeces, regardless of age (p < 0.01). Old dogs presented lower acetate and total short-chain fatty acids (SCFA) and higher lactate and ammonia than adults (p < 0.05). Only for old dogs the intake of the High RS food reduced ammonia and increased faecal lactate (p < 0.05). An age × diet interaction was verified for glucose postprandial response, with lower values for old dogs fed High RS food (p < 0.05), while no differences were found for the other treatments. Old dogs had higher postprandial insulin secretion regardless of the diet (p < 0.05), and lower insulin increment at 180 min after the meal when fed the Low RS than when fed the High RS food (p < 0.05). In conclusion, the diet with lower SG and higher RS improved the intestinal microenvironment, with higher butyrate and total SCFA without altering faeces production or score. Old dogs presented less acetate and total SCFA and higher lactate and ammonia in faeces than adults. The High RS food increased lactate and reduced ammonia in faeces of old dogs, with possible positive influences for gut health. Old dogs had higher postprandial insulin secretion than that of adults to maintain blood glucose, and the diet with higher RS content reduced the postprandial glucose response of old dogs.

Sarcomas and old age: few options for such a large patient population.

Although 40% of cases of soft tissue sarcoma (STS) are diagnosed in patients aged ≥65 years, this group is largely excluded from or under-represented in clinical trials and receives disproportionately less treatment than younger patients. Pooled analyses and subgroup analyses of Phase II and III randomized controlled trials of systemic therapy in advanced STS suggest the need to revisit this treatment paradigm. In various analyses, efficacy outcomes in older patients did not differ from those in younger patients or in the overall population. Available evidence supports treating elderly STS patients with similar treatment as that for younger patients. However, as some treatments are less well tolerated in older patients, safety must be considered when selecting treatment. As physiological rather than chronological age is a more appropriate criterion for treatment selection, geriatric assessment has a central role in trial design and routine clinical practice. The majority of evidence for the efficacy and safety of systemic therapy in elderly, advanced STS patients has been generated with trabectedin, which is the only agent approved for first-line use in patients unsuited to receive doxorubicin-based regimens.

Correlation between chronological and physiological age of males from their multivariate urinary endogenous steroid profile and prostatic carcinoma-induced deviation.

The biosynthesis of endogenous androgenic anabolic steroids (EAAS) in males varies with age. Knowledge of the general urinary EAAS profile's dependence from aging - not reported up to now - may represents a prerequisite for its exploitation in the screening and diagnostic support for several pathologies. Extended urinary EAAS profiles were obtained from healthy and pathological individuals, using a GC-MS method which was fully validated by a stepwise, analyst-independent scheme. Seventeen EAAS and five of their concentration ratios were determined and investigated using multivariate statistical methods. A regression model based on Kernel partial least squares algorithm was built to correlate the chronological age of healthy male individuals with their "physiological age" as determined from their urinary EAAS profile. Strong correlation (R2 = 0.75; slope = 0.747) and good prediction ability of the real chronological age was inferred from EAAS data. In contrast, patients with recent diagnosis (not pharmacologically treated) of prostatic carcinoma (PCa) exhibited a comprehensive EAAS profile with strong negative deviation from the model, corresponding a younger predicted age. This result is possibly related to the activation of anomalous steroid biosynthesis induced from PCa. Over a restricted 60-80 years-old population, PLS-discriminant analysis (DA) was used to distinguish healthy subjects from patients with untreated PCa. PLS-DA yielded excellent discrimination (sensitivity and specificity >90%) between healthy and pathological individuals. This proof-of-concept study provides a preliminary evaluation of multivariate DA on wide EAAS profiles as a screening method to distinguish PCa from non-pathological conditions, overcoming the potentially interfering effect of ageing.

Molecular and phenotypic biomarkers of aging.

Individuals of the same age may not age at the same rate. Quantitative biomarkers of aging are valuable tools to measure physiological age, assess the extent of 'healthy aging', and potentially predict health span and life span for an individual. Given the complex nature of the aging process, the biomarkers of aging are multilayered and multifaceted. Here, we review the phenotypic and molecular biomarkers of aging. Identifying and using biomarkers of aging to improve human health, prevent age-associated diseases, and extend healthy life span are now facilitated by the fast-growing capacity of multilevel cross-sectional and longitudinal data acquisition, storage, and analysis, particularly for data related to general human populations. Combined with artificial intelligence and machine learning techniques, reliable panels of biomarkers of aging will have tremendous potential to improve human health in aging societies.

Validation of the multiplier method for leg-length predictions on a large European cohort and an assessment of the effect of physiological age on predictions.

PURPOSE: The Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort was used to determine the accuracy of the Paley multiplier method for predicting leg length. Using menarche as a proxy, physiological age was then used to increase the accuracy of the multiplier. METHODS: Chronological age was corrected in female patients over the age of eight years with documented date of first menses. Final sub-ischial leg length and predicted final leg length were predicted for all data points. RESULTS: Good correlation was demonstrated between the Paley and ALSPAC data. The average error in prediction depended on the time of assessment, tending to improve as the child got older. It varied from 2.2 cm at the age of seven years to 1.8 cm at the age of 14 years. When chronological age was corrected, the accuracy of multiplier increased. Age correction of 50% improved multiplier predictions by up to 28%. CONCLUSION: There appears to have been no significant change in growth trajectories of the two populations who were chronologically separated by 40 years. While the Paley data were based on extracting trends from averaged data, the ALSPAC dataset provides descriptive statistics from which it is possible to compare populations and assess the accuracy of the multiplier method. The data suggest that the accuracy improves as the patient gets close to the average skeletal maturity but that results need to be interpreted in conjunction with a radiological assessment of the growth plates. The magnitude of the errors in prediction suggest that when using the multiplier, the clinician must remain vigilant and prepared to perform a contralateral epiphyseodisis if the prediction proves to be wrong. The data suggest a relationship between the multiplier and menarche. There appears to be a factorisation and when accounting for physiological age, one needs to correct by 50% of the difference between chronological and physiological age.