Perspective: Promoting Healthy Aging through Nutrition: A Research Centers Collaborative Network Workshop Report.

Within 20 y, the number of adults in the United States over the age of 65 y is expected to more than double and the number over age 85 y is expected to more than triple. The risk for most chronic diseases and disabilities increases with age, so this demographic shift carries significant implications for the individual, health care providers, and population health. Strategies that delay or prevent the onset of age-related diseases are becoming increasingly important. Although considerable progress has been made in understanding the contribution of nutrition to healthy aging, it has become increasingly apparent that much remains to be learned, especially because the aging process is highly variable. Most federal nutrition programs and nutrition research studies define all adults over age 65 y as "older" and do not account for physiological and metabolic changes that occur throughout older adulthood that influence nutritional needs. Moreover, the older adult population is becoming more racially and ethnically diverse, so cultural preferences and other social determinants of health need to be considered. The Research Centers Collaborative Network sponsored a 1.5-d multidisciplinary workshop that included sessions on dietary patterns in health and disease, timing and targeting interventions, and health disparities and the social context of diet and food choice. The agenda and presentations can be found at https://www.rccn-aging.org/nutrition-2023-rccn-workshop. Here we summarize the workshop's themes and discussions and highlight research gaps that if filled will considerably advance our understanding of the role of nutrition in healthy aging.

Assessment of potential biomarkers of subclinical vitamin K deficiency in patients with end-stage kidney disease.

BACKGROUND: A significant proportion of hemodialysis patients have functional, but modifiable, vitamin K deficiency. OBJECTIVE: To determine the correlates of poor vitamin K status in hemodialysis patients. DESIGN: Cross-sectional study. SETTING: Hemodialysis units at Kingston General Hospital and its satellite centres, Ontario, Canada. PATIENTS: Patients undergoing outpatient hemodialysis for end-stage kidney disease. MEASUREMENTS: Serum concentrations of phylloquinone, undercarboxylated prothrombin, also known as protein induced by vitamin K absence or antagonism - factor II (PIVKA-II), and the percentage of undercarboxylated osteocalcin (%ucOC). METHODS: Vitamin K status was determined in fasting blood samples of hemodialysis patients. Bivariate relationships were examined using parametric and non-parametric statistics as appropriate. Multivariable linear regression models were applied to identify predictors of vitamin K status. RESULTS: Among 44 HD patients, criteria for subclinical vitamin K deficiency were met in 13.6% (phylloquinone < 0.4 nmol/L), 51% (%ucOC > 20%) and 90.9% (PIVKA-II > 2.0 nmol/L) of subjects. Phylloquinone levels were positively associated with total cholesterol, triglyceride levels and non-smoking status. Higher %ucOC was associated with increased calcium-phosphate product. Increased PIVKA-II levels were observed with advancing age, reduced dialysis adequacy, lower HDL and a history of coronary artery disease. There were no associations found among the individual biomarkers of vitamin K status. In a multi-variable model, triglycerides were the only significant predictor of phylloquinone levels, while increasing phosphate and decreasing PTH were independent predictors of %ucOC. PIVKA-II levels increased by 0.54 nmol/L for every 10-year increase in age. LIMITATIONS: Observational study; small sample size. CONCLUSIONS: A significant proportion of HD patients met criteria for subclinical vitamin K deficiency. Of the biomarkers measured, PIVKA-II may be superior given its independence of renal function or dyslipidemia, both of which may confound the other vitamin K biomarkers. Studies in patients with ESKD linking biomarkers of vitamin K status to important patient outcomes, including cardiovascular disease, nutritional status and mortality, are required in order to determine the optimal biomarker for evaluating vitamin K status in this particular population.

CONTEXTE: Une proportion considérable de patients traités en hémodialyse ont une carence fonctionnelle, bien que modifiable, en vitamine K. L'objectif de cette étude est de déterminer la corrélation entre une carence en vitamine K chez les patients en hémodialyse. MÉTHODES: Dans le cadre de cette étude d'observation, le statut de la vitamine K était déterminé dans les échantillons sanguins pris à jeun chez 44 patients en hémodialyse, en mesurant les concentrations de phylloquinone, de prothrombine non décarboxylée, aussi connue comme la protéine induite en l'absence de vitamine K ou par antagonisme du facteur II (PIVKA-II), et le pourcentage d'ostéocalcine non décarboxylée (%ucOC). Les relations bivariées ont été examinées à l'aide de statistiques paramétriques et non paramétriques. Des modèles multivariés à régression linéaire ont été appliqués pour déterminer les prédicteurs du statut de la vitamine K. RÉSULTATS: Les critères de carence infraclinique en vitamine K étaient remplis chez 13,6% (phylloquinone < 0,4 nmol/l), 51% (%ucOC > 20%) et 90,9% (PIVKA-II > 2,0 nmol/l) des sujets. Les taux de phylloquinone ont été positivement associés avec les taux de cholestérol total, et de triglycérides, ainsi que le statut de non-fumeur. Un taux élevé de %ucOC a été associé avec une augmentation du produit phosphocalcique. Des taux croissants de PIVKA-II ont été observés avec l'âge, le caractère non adéquat de la dialyse, un faible taux de HDL et des antécédents de coronaropathie. Aucune association n'a été établie parmi les biomarqueurs individuels du statut de la vitamine K. Dans un modèle multivariable, les triglycérides constituaient le seul prédicteur important des taux de phylloquinone, alors qu'un taux croissant de phosphate et un taux décroissant de PTH étaient des prédicteurs indépendants de %ucOC. Les taux de PIVKA-II ont augmenté de 0,54 nmol/l par tranche d'âge de 10 ans. CONCLUSIONS: Une proportion considérable de patients en hémodialyse ont rempli les critères de carence infraclinique en vitamine K. Parmi les biomarqueurs mesurés, PIVKA-II serait le plus fiable, considérant son indépendance par rapport à la fonction rénale ou la dyslipidémie, lesquels peuvent confondre les autres biomarqueurs de la vitamine K. Des études auprès de patients souffrant d'insuffisance rénale terminale permettraient de créer des liens entre les biomarqueurs du statut de la vitamine K et des résultats importants pour le patient, tels que les maladies cardiovasculaires, l'état nutritionnel et le décès, et seraient donc nécessaires afin de déterminer le biomarqueur optimal pour évaluer le statut de la vitamine K dans cette population en particulier.

Imbalance between neutrophil elastase and its inhibitor α1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure.

The molecular mechanisms involved in the development of obesity and related complications remain unclear. Here, we report that obese mice and human subjects have increased activity of neutrophil elastase (NE) and decreased serum levels of the NE inhibitor α1-antitrypsin (A1AT, SerpinA1). NE null (Ela2(-/-)) mice and A1AT transgenic mice were resistant to high-fat diet (HFD)-induced body weight gain, insulin resistance, inflammation, and fatty liver. NE inhibitor GW311616A reversed insulin resistance and body weight gain in HFD-fed mice. Ela2(-/-) mice also augmented circulating high molecular weight (HMW) adiponectin levels, phosphorylation of AMP-activated protein kinase (AMPK), and fatty acid oxidation (FAO) in the liver and brown adipose tissue (BAT) and uncoupling protein (UCP1) levels in the BAT. These data suggest that the A1AT-NE system regulates AMPK signaling, FAO, and energy expenditure. The imbalance between A1AT and NE contributes to the development of obesity and related inflammation, insulin resistance, and liver steatosis.