The association of protein-bound methionine sulfoxide with proteomic basis for aging in beech seeds.

BACKGROUND: European beech (Fagus sylvatica L.) trees produce seeds irregularly; therefore, it is necessary to store beech seeds for forestation. Despite the acquisition of desiccation tolerance during development, beech seeds are classified as intermediate because they lose viability during long-term storage faster than typical orthodox seeds. In this study, beech seeds stored for short (3 years) or long (20 years) periods under optimal conditions and displaying 92 and 30% germination capacity, respectively, were compared. RESULTS: Aged seeds displayed increased membrane damage, manifested as electrolyte leakage and lipid peroxidation levels. Analyses have been based on embryonic axes, which contained higher levels of reactive oxygen species (ROS) and higher levels of protein-bound methionine sulfoxide (MetO) in aged seeds. Using label-free quantitative proteomics, 3,949 proteins were identified, of which 2,442 were reliably quantified pointing to 24 more abundant proteins and 35 less abundant proteins in beech seeds under long-term storage conditions. Functional analyses based on gene ontology annotations revealed that nucleic acid binding activity (molecular function), ribosome organization or biogenesis and transmembrane transport (cellular processes), translational proteins (protein class) and membranous anatomical entities (cellular compartment) were affected in aged seeds. To verify whether MetO, the oxidative posttranslational modification of proteins that can be reversed via the action of methionine sulfoxide reductase (Msr) enzymes, is involved in the aging of beech seeds, we identified and quantified 226 MetO-containing proteins, among which 9 and 19 exhibited significantly up- and downregulated MetO levels, respectively, in beech seeds under long-term storage conditions. Several Msr isoforms were identified and recognized as MsrA1-like, MsrA4, MsrB5 and MsrB5-like in beech seeds. Only MsrA1-like displayed decreased abundance in aged seeds. CONCLUSIONS: We demonstrated that the loss of membrane integrity reflected in the elevated abundance of membrane proteins had a higher impact on seed aging progress than the MetO/Msr system. Proteome analyses enabled us to propose protein Sec61 and glyceraldehyde-3-phosphate dehydrogenase as potential longevity modulators in beech seeds.

Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies.

SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) αß sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. Highly expanded 199 TCR clonotypes upon stimulation with S peptide pools were reconstituted into a reporter T cell line for the determination of epitopes and restricting HLAs. Among them, we could determine 78 S epitopes, most of which were conserved in variants of concern (VOCs). After the 2nd vaccination, T cell clonotypes highly responsive to recall S stimulation were polarized to follicular helper T (Tfh)-like cells in donors exhibiting sustained anti-S antibody titers (designated as 'sustainers'), but not in 'decliners'. Even before vaccination, S-reactive CD4+ T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic microbes. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest that de novo acquisition of memory Tfh-like cells upon vaccination may contribute to the longevity of anti-S antibody titers.

Characterization of Biologic Discontinuation Among Pediatric Patients with Crohn's Disease.

BACKGROUND AND AIMS: Biologic therapies may effectively treat Crohn's disease (CD), and pediatric patients who discontinue multiple biologics risk exhausting treatment options. The frequency and context of biologic discontinuation has not been well characterized. We aimed to determine patterns of biologic use, discontinuation, and evaluation in pediatric patients with CD. METHODS: Pediatric patients with CD at seven US centers (2010-2020) were identified. Prospective ImproveCareNow registry data were supplemented with medical record abstraction. Biologics included monoclonal antibody and small molecule medications. Therapeutic drug monitoring (TDM) was considered induction if <14 weeks after biologic start, proactive if later during quiescent disease, and reactive during active disease. RESULTS: Of 823 patients included (median age 13.0 years, 40% female), 86% started biologics (78% infliximab, 21% adalimumab, <1% others). 26% used concomitant immunomodulators for ≥12 months. Most (85%) measured TDM including 47% induction, 69% proactive, and 24% reactive. 29% discontinued their first biologic after median 793 days due to inefficacy (34%), anti-drug antibodies (8%), adverse events (8%), or non-adherence (12%). If inefficacy, 86% underwent pre-discontinuation evaluation. If infliximab or adalimumab inefficacy and TDM was done, 62% had levels <10 µg/ml. Proactive TDM and concomitant immunomodulators were associated with 60% and 32% reduced biologic discontinuation. CONCLUSION: Most children with CD are treated with biologics, 25-37% discontinue biologics resulting in 1 in 12 using >2 biologics during pediatric care. Half of patients discontinued biologics without trial of high-dose therapy, and 14% without any evaluation. Concomitant immunomodulator use and proactive TDM decreased risk of biologic discontinuation. Strategies are needed to preserve biologic efficacy and prevent biologic discontinuation.

Bond strength and marginal adaptation of resin composites and correlations with clinical results.

OBJECTIVES: Due to innumerable confounding factors and a high number of types and brands of dental restorative materials, the clinical performance of restorative materials are sought predicted by various in vitro tests. However, only few such tests have been found to correlate well with clinical findings. Thus, the present study determined the in vitro dentin bond strength and marginal adaptation of Class II restorations and correlated the results to their clinical outcomes. METHODS: Dentin bond strength (µTBS and µSBS) and marginal gap formation of Class II restorations (replica technique and SEM) were measured after 24 h and 6 m water storage using eight combinations of adhesive and resin composite. Clinical outcomes (mean survival time, Hazard Ratio, annual failure rate; n = 10.695) were gained from a data set of a retrospective multicenter study of direct restorations. RESULTS: Significant differences were found for dentin bond strength and marginal gap formation between the restorative material groups, and negative effects of long-term storage were observed. µTBS correlated significantly with certain clinical outcomes of Class I restorations, while µSBS correlated with certain clinical outcomes of Class II, III, IV and V restorations. Marginal gap formation in enamel and number of paramarginal fractures correlated with certain clinical outcomes of Class II restorations. SIGNIFICANCE: Using the same restorative materials in vitro as in vivo, gave significant, but weak correlations between in vitro bond strength or marginal adaptation and clinical outcomes, lending support to the use of in vitro tests in early stages of material selection.

Intensive antihypertensive treatment does not lower cerebral blood flow or cause orthostatic hypotension in frail older adults.

This study aimed to examine the effects of intensive antihypertensive treatment (AHT), i.e., systolic blood pressure target ≤ 140 mmHg, on cerebral blood flow, cerebral autoregulation, and orthostatic hypotension, in a representative population of frail older adults. Fourteen frail hypertensive patients (six females; age 80.3 ± 5.2 years; Clinical Frailty Scale 4-7; unattended SBP ≥ 150 mmHg) underwent measurements before and after a median 7-week AHT targeting SBP ≤ 140 mmHg. Transcranial Doppler measurements of middle cerebral artery velocity (MCAv), reflecting changes in cerebral blood flow (CBF), were combined with finger plethysmography recordings of continuous BP. Transfer function analysis assessed cerebral autoregulation (CA). ANCOVA analysed AHT-induced changes in CBF and CA and evaluated non-inferiority of the relative change in CBF (margin: -10%; covariates: pre-AHT values and AHT-induced relative mean BP change). McNemar-tests analysed whether the prevalence of OH and initial OH, assessed by sit/supine-to-stand challenges, increased with AHT. Unattended mean arterial pressure decreased by 15 mmHg following AHT. Ten (71%) participants had good quality TCD assessments. Non-inferiority was confirmed for the relative change in MCAv (95%CI: -2.7, 30.4). CA remained normal following AHT (P > 0.05), and the prevalence of OH and initial OH did not increase (P ≥ 0.655). We found that AHT in frail, older patients does not reduce CBF, impair autoregulation, or increase (initial) OH prevalence. These observations may open doors for more intensive AHT targets upon individualized evaluation and monitoring of hypertensive frail patients.Clinical Trial Registration: This study is registered at ClinicalTrials.gov (NCT05529147; September 1, 2022) and EudraCT (2022-001283-10; June 28, 2022).

Intracellular cytokines in peritoneal leukocytes relate to lifespan in aging and long-lived female mice.

Peritoneal immune cell function is a reliable indicator of aging and longevity in mice and inflammaging is associated with a shorter lifespan. Nevertheless, it is unknown if the content of cytokines in these immune cells is linked to individual differences in lifespan. Therefore, this work aimed to investigate different peritoneal leukocyte populations and their content in intracellular pro-inflammatory (TNF and IL-6) and anti-inflammatory (IL-10) cytokines by flow cytometry in adult (10 months-old, n = 8) and old (18 months-old, n = 20) female Swiss/ICR mice. In addition, old mice were monitored longitudinally throughout their aging process, and the same markers were analyzed at the very old (24 months-old, n = 8) and long-lived (30 months-old, n = 4) ages. The longitudinal follow-up allowed us to relate the investigated parameters to individual lifespans. The results show that long-lived female mice exhibit an adult-like profile in most parameters investigated but also display specific immune adaptations, such as increased CD4+ and CD8+ T cells containing the pro-inflammatory TNF cytokine and CD4+ T cells and macrophages containing the anti-inflammatory cytokine IL-10. These adaptations may underlie their exceptional longevity. In addition, a negative correlation was obtained between the percentage of cytotoxic T cells, KLRG-1/CD4, large peritoneal macrophages, and the percentage of CD4+ T cells containing IL-6 and macrophages containing IL-10 in old age and lifespan, whereas a positive correlation was found between the CD4/CD8 ratio and the longevity of the animals at the same age. These results highlight the crucial role of peritoneal leukocytes in inflammaging and longevity.

Overexpression of Larch SCL6 Inhibits Transitions from Vegetative Meristem to Inflorescence and Flower Meristem in Arabidopsis thaliana (L.) Heynh.

SCARECROW-LIKE6 (SCL6) plays a role in the formation and maintenance of the meristem. In Larix kaempferi (Lamb.) Carr., an important afforestation tree species in China, SCL6 (LaSCL6) has two alternative splicing variants-LaSCL6-var1 and LaSCL6-var2-which are regulated by microRNA171. However, their roles are still unclear. In this study, LaSCL6-var1 and LaSCL6-var2 were transformed into the Arabidopsis thaliana (L.) Heynh. genome, and the phenotypic characteristics of transgenic A. thaliana, including the germination percentage, root length, bolting time, flower and silique formation times, inflorescence axis length, and branch and silique numbers, were analyzed to reveal their functions. It was found that LaSCL6-var1 and LaSCL6-var2 overexpression shortened the root length by 41% and 31%, respectively, and increased the inflorescence axis length. Compared with the wild type, the bolting time in transgenic plants was delayed by approximately 2-3 days, the first flower and silique formation times were delayed by approximately 3-4 days, and the last flower and silique formation times were delayed by about 5 days. Overall, the life cycle in transgenic plants was prolonged by approximately 5 days. These results show that LaSCL6 overexpression inhibited the transitions from the vegetative meristem to inflorescence meristem and from the flower meristem to meristem arrest in A. thaliana, revealing the roles of LaSCL6-var1 and LaSCL6-var2 in the fate transition and maintenance of the meristem.

Outrunning the grim reaper: longevity of the first 200 sub-4 min mile male runners.

OBJECTIVES: To determine the impact of running a sub-4 min mile on longevity. It was hypothesised that there would be an increase in longevity for runners who successfully completed a sub-4 min mile compared with the general population. METHODS: As part of this retrospective cohort study, the Sub-4 Alphabetic Register was used to extract the first 200 athletes to run a sub-4 min mile. Each runner's date of birth, date of their first successful mile attempt, current age (if alive) or age at death was compared with the United Nations Life Tables to determine the difference in each runner's current age or age at death with their country of origin-specific life expectancy. RESULTS: Of the first 200 sub-4 min mile runners (100% male), 60 were dead (30%) and 140 were still alive. Sub-4 min mile runners lived an average of 4.7 years beyond their predicted life expectancy (95% CI 4.7 to 4.8). When accounting for the decade of completion (1950s, 1960s or 1970s), the longevity benefits were 9.2 years (n=22; 95% CI 8.3 to 10.1), 5.5 years (n=88; 95% CI 5.3 to 5.7) and 2.9 years (n=90; 95% CI 2.7 to 3.1), respectively. CONCLUSION: Sub-4 min mile runners have increased longevity compared with the general population, thereby challenging the notion that extreme endurance exercise may be detrimental to longevity.

Specific differences and novel key regulatory genes of sex in influencing exceptional longevity phenotypes.

BACKGROUND AND AIMS: Although the life expectancy of women systematically and robustly exceeds that of men, specific differences and molecular mechanisms of sex in influencing longevity phenotypes remain largely unknown. Therefore, we performed transcriptome sequencing of peripheral blood samples to explore regulatory mechanisms of healthy longevity by incorporating sex data. METHODS: We selected 34 exceptional longevity (age: 98.26 ± 2.45 years) and 16 controls (age: 52.81 ± 9.78) without advanced outcomes from 1363 longevity and 692 controls recruited from Nanning of Guangxi for RNA sequencing 1. The transcriptome sequencing 1 data of 50 samples were compared by longevity and sex to screen differentially expressed genes (DEGs). Then, 121 aging samples (40-110 years old) without advanced outcomes from 355 longevity and 294 controls recruited from Dongxing of Guangxi were selected for RNA sequencing 2. The genes associated with aging from the transcriptome sequencing 2 of 121 aging samples were filtered out. Finally, the gender-related longevity candidate genes and their possible metabolic pathways were verified by cell model of aging and a real-time polymerase chain reaction (RT-PCR). RESULTS: Metabolism differs between male and female and plays a key role in longevity. Moreover, the principal findings of this study revealed a novel key gene, UGT2B11, that plays an important role in regulating lipid metabolism through the peroxisome proliferator activated receptor gamma (PPARG) signalling pathway and ultimately improving lifespan, particularly in females. CONCLUSION: The findings suggest specific differences in metabolism affecting exceptional longevity phenotypes between the sexes and offer novel therapeutic targets to extend lifespan by regulating lipid homeostasis.

Health and wellbeing status of the long-lived individuals of the Spanish LONGECYL cross-sectional study.

BACKGROUND: The increase in life expectancy and long-lived individuals is a challenge for public health and provides an opportunity to understand the determinants of longevity. However, few studies have addressed the factors associated with the health status and quality of life in a long-lived individual population. We described the perceived health, clinical status, quality of life, and dependency for activities of daily living in a representative population in Castile and Leon, Spain. METHODS: A sample of 759 long-lived individuals aged 95 years and older was studied by the Health Sentinel Network of Castile and Leon (Spain) through a health examination and a structured questionnaire covering quality of life (EQ-5D-3), lifestyle habits, diet, working life and family health. A blood sample was taken for the study of biological and genetic markers. Chi Square and logistic regression OR with 95% confidence intervals were used to analyze the determinants of the long-lived individuals' health status. The significant level for the bivariate analysis was established at 0.05. RESULTS: Perceived health was good, very good or excellent in 64.2%, while only 46.0% had a quality-of-life index above 0.5 (ranging from 0 to 1) and 44.1% maintained acceptable independence for activities of daily living. Quality-of-life index was higher in the oldest, (OR 7.98 [2,32-27.41]) above 100 years compared to those under 98, and men had better values for independence than women (OR 2.43 [1.40-4.29]). Cardiovascular diseases were the most prevalent (85.5%), but neurological and mental diseases and vision problems had the highest impact on quality of life and independence. CONCLUSION: The long-lived individuals of Castile and Leon have a relatively well-preserved health status, although the perception of health is higher than that describing their quality of life and dependence. The quality of life was higher in the oldest age group and showed differences according to sex, with a better quality of life in men. Public health policies and programs should take in account the differences by sex and age as well as the prevention and control of the main conditions related with poor quality of life or dependence. Future research must include the interaction among genetic, socioeconomic, environmental, and other clinical factors in the quality of life and disability of long-lived individuals.

Key determinants of adaptive strategies of goats to a 2-day nutritional challenge during early lactation.

Little is known about the key determinants of the physiological adaptations to environmental challenges and how these determinants interact. We evaluated how the response/recovery profiles to a short-term nutritional challenge during early lactation are affected by early-life nutritional strategies in dairy goats divergently selected for functional longevity. We used 72 females, split into two cohorts, daughters of Alpine bucks divergently selected for functional longevity. The females from the two lines were fed with two divergent diets, normal vs low-energy, from weaning until the middle of first gestation, and then fed with the same standard diet. Individual BW, body condition score, morphology, and plasma samples were collected from birth to first kidding. The adaptative physiological strategy to a nutritional challenge was assessed via a 2-day feed restriction challenge, during early lactation, which consisted of a five-day control period on a standard lactation diet followed by a 2-day challenge with straw-only feeding and then a 10-day recovery period on a standard lactation diet. During the challenge, DM intake, BW, milk yield (MY), and plasma and milk metabolite composition were recorded daily. Linear mixed-effects models were used to analyze all traits, considering the individual nested in the cohort as a random effect and the 2 × 2 treatments (i.e., line and rearing diet) and litter size as fixed effects. Linear mixed-effects models using a piecewise arrangement were used to analyze the response/recovery profiles to nutritional challenge. Random parameters estimated for each individual, using the mixed-effects models without the fixed effects of rearing diet and genetic line, were used in a stepwise model selection based on R2 to identify key determinants of an individual's physiological adaptations to environmental challenges. Differences in stature and body reserves created by the two rearing diets diminished during late gestation and the 5-day control period. Genetic line did not affect body reserves during the rearing phase. Rearing diet and genetic line slightly affected the recovery profiles of evaluated traits and had no effects on prechallenge and response to challenge profiles. The prekidding energy status measures and MY before challenge were selected as strong predictors of variability in response-recovery profiles of milk metabolites that have strong links with body energy dynamics (i.e., isoCitrate, ß-hydroxybutyrate, choline, cholesterol, and triacylglycerols; R2 = 35%). Our results suggested that prekidding energy status and MY are key determinants of adult resilience and that rearing diet and genetic line may affect adult resilience insofar as they affect the animals' energy status.

Meat-Egg-Dairy Consumption and Frailty among Chinese Older Adults: Exploring Rural/Urban and Gender Differences.

The dietary patterns of older adults, particularly in relation to meat, egg, and dairy (MED) consumption, significantly impact frailty, a state of heightened vulnerability to adverse health outcomes. This paper investigates the association between MED consumption and frailty among older Chinese adults, considering rural/urban disparities and gender differences. Analyzing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) spanning from 2008 to 2018, this study explores how MED consumption influences frailty levels over time. The results show that moderate MED consumption is associated with slower frailty progression, suggesting a protective effect against frailty among older adults. However, excessive MED consumption, particularly among rural residents and females, is linked to accelerated frailty progression. Urban residents and males report higher MED consumption levels, possibly due to their greater access to diverse food options and traditional dietary preferences. The findings underscore the complex interplay between dietary habits, demographic factors, and frailty outcomes. Understanding these dynamics is crucial for developing targeted interventions to mitigate frailty risk factors and promote healthy aging among Chinese older adults.

The world's longest lasting VVI pacemaker device for over 40 years.

INTRODUCTION: Implantable permanent pacemaker function is supported by their energy sources for a mean period of 8.8-12.4 years. We previously published this case of a patient with a normally functioning VVI pacemaker, 31 years after implantation. METHODS AND RESULTS: In this report, we state that the device is still functioning normally 40 years after implantation. The most recent device interrogation revealed pacing threshold of 0.9 V/0.5 ms. Holter monitoring for 24 hours recorded a total of 98.707 beats with 97.78% paced beats, without any indication of pacemaker malfunction and with stable heart rate at 70-71 bpm. CONCLUSION: Most patients with implantable devices have the appropriate follow-up and settings of low energy consumption. Manufacturing companies should focus on prolonging device longevity, to produce future devices with higher energy capacity.

Utilizing genetics and proteomics to assess the role of antihypertensive drugs in human longevity and the underlying pathways: a Mendelian randomization study.

BACKGROUND: Antihypertensive drugs are known to lower cardiovascular mortality, but the role of different types of antihypertensive drugs in lifespan has not been clarified. Moreover, the underlying mechanisms remain unclear. METHODS: To minimize confounding, we used Mendelian randomization to assess the role of different antihypertensive drug classes in longevity and examined the pathways via proteins. Genetic variants associated with systolic blood pressure (SBP) corresponding to drug target genes were used as genetic instruments. The genetic associations with lifespan were obtained from a large genome-wide association study including 1 million European participants from UK Biobank and LifeGen. For significant antihypertensive drug classes, we performed sex-specific analysis, drug-target analysis and colocalization. To examine the mediation pathways, we assessed the associations of 2291 plasma proteins with lifespan, and examined the associations of drug classes with the proteins affecting lifespan. RESULTS: After correcting for multiple testing, genetically proxied beta-blockers (BBs), calcium channel blockers (CCBs) and vasodilators were related to longer life years (BBs: 2.03, 95% CI 0.78 to 3.28 per 5-mmHg reduction in SBP, CCBs: 3.40, 95% CI 1.47 to 5.33, and vasodilators: 2.92, 95% CI 1.08 to 4.77). The beneficial effects of BBs and CCBs were more obvious in men. ADRB1, CACNA2D2, CACNB3, CPT1A, CPT2, and EDNRA genes were related to extended lifespan with CPT2 further supported by colocalization evidence. 86 proteins were related to lifespan, of which 4 proteins were affected by CCBs. CDH1 may mediate the association between CCBs and lifespan. CONCLUSIONS: BBs, CCBs and vasodilators may prolong lifespan, with potential sex differences for BBs and CCBs. The role of CCBs in lifespan is partly mediated by CDH1. Prioritizing the potential protein targets can provide new insights into healthy aging.

Measuring Replicative Lifespan in Cryptococcus neoformans.

Advances in understanding cellular aging research have been possible due to the analysis of the replicative lifespan of yeast cells. Studying longevity in the pathogenic yeast Cryptococcus neoformans is essential because old yeast cells with age-related phenotypes accumulate during infection and are associated with increased virulence and antifungal tolerance. Microdissection and microfluidic devices are valuable tools for continuously tracking cells at the single-cell level. In this chapter, we describe the features of these two platforms and outline technical limitations and information to study aging mechanisms while assessing the lifespan of yeast cells.

Glial overexpression of Tspo extends lifespan and protects against frataxin deficiency in Drosophila.

The translocator protein TSPO is an evolutionary conserved mitochondrial protein overexpressed in various contexts of neurodegeneration. Friedreich Ataxia (FA) is a neurodegenerative disease due to GAA expansions in the FXN gene leading to decreased expression of frataxin, a mitochondrial protein involved in the biosynthesis of iron-sulfur clusters. We previously reported that Tspo was overexpressed in a Drosophila model of this disease generated by CRISPR/Cas9 insertion of approximately 200 GAA in the intron of fh, the fly frataxin gene. Here, we describe a new Drosophila model of FA with 42 GAA repeats, called fh-GAAs. The smaller expansion size allowed to obtain adults exhibiting hallmarks of the FA disease, including short lifespan, locomotory defects and hypersensitivity to oxidative stress. The reduced lifespan was fully rescued by ubiquitous expression of human FXN, confirming that both frataxins share conserved functions. We observed that Tspo was overexpressed in heads and decreased in intestines of these fh-GAAs flies. Then, we further overexpressed Tspo specifically in glial cells and observed improved survival. Finally, we investigated the effects of Tspo overexpression in healthy flies. Increased longevity was conferred by glial-specific overexpression, with opposite effects in neurons. Overall, this study highlights protective effects of glial TSPO in Drosophila both in a neurodegenerative and a healthy context.

Factors of food choice and nutritional intake of Brazilian older adults according sociodemographic and health characteristics.

The rapid demographic transition in developing countries has always posed a challenge for the social and economic policies of these nations. The increase in longevity poses new challenges for understanding dietary consumption among different age groups at the old age population. The aim of this study was to evaluate the reasons for food choice and the composition of nutritional intake of older adults and its relationship to individual characteristics. Community-living older adults aged 60 and older were interviewed in their homes at the southeastern region of Brazil, between December 2021 and February 2022. The Food Choice Questionnaire and a Food Frequency Questionnaire were administered to obtain data on the reasons for food choice and nutritional intake. A structured interview was employed to gather information on individual characteristics. 168 older adults (mean age of 72.6 ± 8.9; 69.6% women) participated. The reasons for food choice differed significantly, with weight control being one of the least important and health being one of the most important. But older adults aged 80 and over valued the health criterion less than younger participants (60-69 years old). The intake of macronutrients and energy were below nutritional recommendations. Carbohydrate consumption was positively correlated with the mood motive. There was a relationship between the reasons for choosing food and/or the components of nutritional intake with: gender, age, living with a partner, self-report of depression/anxiety, self-perception of health and nutritional status anthropometric. The results are important to be considered in prevention policies and clinical-nutritional management, with special attention to the oldest-old.

Amino acid restriction, aging, and longevity: an update.

Various so-called dietary restriction paradigms have shown promise for extending health and life. All such paradigms rely on ad libitum (hereafter ad lib) feeding, something virtually never employed in animals whose long-term health we value, either as a control or, except for food restriction itself, for both control and treatment arms of the experiment. Even though the mechanism(s) remain only vaguely understood, compared to ad lib-fed animals a host of dietary manipulations, including calorie restriction, low protein, methionine, branched-chain amino acids, and even low isoleucine have demonstrable health benefits in laboratory species in a standard laboratory environment. The remaining challenge is to determine whether these health benefits remain in more realistic environments and how they interact with other health enhancing treatments such as exercise or emerging geroprotective drugs. Here we review the current state of the field of amino acid restriction on longevity of animal models and evaluate its translational potential.

Life expectancy gains from dietary modifications: a comparative modeling study in 7 countries.

BACKGROUND: Eating healthier is associated with a range of favorable health outcomes. Our previous model estimated the impact of dietary changes on life expectancy gains but did not consider height, weight, or physical activity. OBJECTIVES: We aimed to estimate the increase in life expectancy resulting from the transition from typical national dietary patterns to longevity-optimizing dietary changes, more feasible dietary modifications, and optimized vegan dietary changes in China, France, Germany, Iran, Norway, the United Kingdom, and the United States. METHODS: Our modeling study used data from meta-analyses presenting dose-response relationships between intake of 15 food groups and mortality. Background mortality data were from the Global Burden of Disease Study. We used national food intake data and adjusted for height, weight, and physical activity level. RESULTS: For 40-y-olds, estimated life expectancy gains ranged from 6.2 y (with uncertainty interval [UI]: 5.7, 7.5 y) for Chinese females to 9.7 y (UI: 8.1, 11.3 y) for United States males following sustained changes from typical country-specific dietary patterns to longevity-optimized dietary changes, and from 5.2 y (UI: 4.0, 6.5 y) for Chinese females to 8.7 y (UI: 7.1, 10.3 y) for United States males following changes to optimized vegan dietary changes. CONCLUSIONS: A sustained change from country-specific typical dietary pattern patterns to longevity-optimized dietary changes, more feasible dietary changes, or optimized vegan dietary changes are all projected to result in substantial life expectancy gains across ages and countries. These changes included more whole grains, legumes, and nuts and less red/processed meats and sugars and sugar-sweetened beverages. The largest gains from dietary changes would be in the United States.

Artificial Intelligence Assessment of Biological Age from Transthoracic Echocardiography: Discrepancies to Chronologic Age Predict Significant Excess Mortality.

BACKGROUND: Age and sex can be estimated by artificial intelligence based on various sources. OBJECTIVES: We aimed to test whether convolutional neural networks could be trained to estimate the age and predict the sex using standard transthoracic echocardiography (TTE), and to evaluate its prognostic implications. METHODS: The algorithm was trained on 76,342 patients, validated in 22,825 patients, and tested in 20,960 patients. It was then externally validated using data from a different hospital (N=556). Finally, a prospective cohort of handheld point-of-care ultrasound (POCUS) devices (N=319; ClinicalTrials.Gov NCT05455541) was used to confirm the findings. Multivariate Cox regression model was used to investigate the association between age-estimation and chronological age with overall survival. RESULTS: The mean average error in age estimation was 4.9 years, with a Pearson correlation coefficient of 0.922. The probabilistic value of sex had an overall accuracy of 96.1% and an area under the curve (AUC) of 0.993. External validation and prospective study cohorts yielded consistent results. Finally, survival analysis demonstrated that age prediction ≥ 5 years of chronological age was associated with an independent 34% increased risk of death during follow-up (p<0.001). CONCLUSIONS: Applying artificial intelligence to the standard TTE allows prediction of sex and estimation of age. Machine-based estimation is an independent predictor of overall survival and, with further evaluation, can be used for risk stratification and estimation of biological age.