As the proportion of aging people in our population increases steadily, global strategies accompanied by extensive research are necessary to tackle society and health service challenges. The World Health Organization recently published an action plan: "Decade of healthy aging 2020-2030", which calls for concerted collaboration to prevent poverty of older people to provide quality education, job opportunities, and an age-inclusive infrastructure. However, scientists worldwide still struggle to find definitions and appropriate measurements of aging per se and healthy aging in particular. This literature review aims to compile concepts of healthy aging and provide a condensed overview of the challenges in defining and measuring it, along with suggestions for further research. We conducted three independent systematic literature searches covering the main scopes addressed in this review: (1) concepts and definitions of healthy aging, (2) outcomes and measures in (healthy) aging studies and (3) scores and indices of healthy aging. For each scope, the retrieved literature body was screened and subsequently synthesized. We provide a historical overview of the concepts of healthy aging over the past 60 years. Furthermore, we identifiy current difficulties in identifying healthy agers, including dichotomous measurements, illness-centered views, study populations & designs. Secondly, markers and measures of healthy aging are discussed, including points to consider, like plausibility, consistency, and robustness. Finally, we present healthy aging scores as measurements, which combine multiple aspects to avoid a dichotomous categorization and display the bio-psycho-social concept of healthy aging. When deducting research, scientists need to consider the diverse challenges in defining and measuring healthy aging. Considering that, we recommend scores that combine multiple aspects of healthy aging, such as the Healthy Ageing Index or the ATHLOS score, among others. Further efforts are to be made on a harmonized definition of healthy aging and validated measuring instruments that are modular, easy to apply and provide comparable results in different studies and cohorts to enhance the generalization of results.

Advanced glycation end products (AGEs) result from a non-enzymatic reaction of proteins with reactive carbohydrates. Heat-processed food, such as bread, contains high amounts of AGEs. The activation of the NF-κB signaling pathway by bread crust extract (BCE) is well understood. However, it is largely unknown whether NRF2, the master regulator of oxidative stress resistance in mammalian cells, is affected by BCE. We have investigated the molecular mechanisms by which BCE induces antioxidant gene expression in cellular models. Our data showed that soluble extracts from bread crust are capable of stimulating the NRF2 signaling pathway. Furthermore, NRF2 pathway activation was confirmed by microarray and reporter-cell analyses. QRT-PCR measurements and Western blot analyses indicated an induction of antioxidative genes such as HMOX1, GCLM and NQO1 upon BCE treatment. Moreover, BCE pretreated cells had a survival advantage compared to control cells when exposed to oxidative stress. BCE induces phosphorylation of AKT and ERK kinase in EA.hy926 cells. By mass spectrometry, several new, potentially active modifications in BCE were identified. Our findings indicate that BCE activates NRF2-dependent antioxidant gene expression, thus provoking a protection mechanism against oxidative stress-mediated tissue injury. Hence, BCE can be considered as functional food with antioxidative and cardioprotective potential.

Background: Donation after circulatory death (DCD) hearts have to withstand ischemia/reperfusion injury that is partially driven by proinflammatory cytokines and decreases ventricular contractility. We hypothesize that cytokine adsorption during normothermic ex vivo blood perfusion of DCD hearts reduces the cytokine levels and improves ventricular contractility. Methods and Results: Porcine DCD hearts were maintained 4 hours by ex vivo blood perfusion with (DCD‐BP ^CytoS , all groups: N=8) or without (DCD‐BP) CytoSorb, followed by 2 hours reperfusion with fresh blood, including left ventricular functional analysis using a balloon catheter. In a control and a DCD group, hearts were evaluated after procurement. We determined lactate and cytokines after ex vivo blood perfusion and the myocardial and left anterior descending artery transcriptome using microarrays after reperfusion. In DCD‐BP ^CytoS , the developed pressure (control: 124±7 mm Hg/s, DCD: 86±4 mm Hg/s, DCD‐BP: 69±11 mm Hg/s, DCD‐BP ^CytoS : 112±9 mm Hg/s; P <0.05) and maximal slope of pressure increment (control: 2010±39 mm Hg/s, DCD: 1219±164 mm Hg/s, DCD‐BP: 964±163 mm Hg/s, DCD‐BP ^CytoS : 1794±205 mm Hg/s; P <0.05) were higher compared with DCD‐BP and DCD hearts. However, contractility decreased later during reperfusion without CytoSorb. After 4 hours, troponin, lactate (45±5% versus 69±9%, P <0.05), IL (interleukin)‐1β, ‐1ra, and ‐8 were lower in DCD‐BP ^CytoS hearts. In the myocardium of DCD‐BP ^CytoS compared with DCD‐BP hearts, inflammatory mediator receptor activity/binding pathways were enriched, and pathways for collagen‐containing extracellular matrix and contractile fiber were underrepresented. In the left anterior descending artery of DCD‐BP ^CytoS hearts, serine/threonine/tyrosine kinase activity and wound‐healing pathways were enriched, and mitochondrial protein‐containing complex and respiratome‐associated pathways were underrepresented. Conclusions: CytoSorb during ex vivo blood perfusion enhances the maintenance of DCD hearts and is likely to improve graft function after transplantation.

Background: The diagnosis of Alzheimer’s disease (AD) relies on core cerebrospinal fluid (CSF) biomarkers, amyloid beta (Aβ) and tau. As the brain is then already damaged, researchers still strive to discover earlier biomarkers of disease onset and the progression of AD. Glycation, advanced glycation end products (AGEs) and oxidative modifications on proteins in CSF mirror the underlying biological mechanisms that contribute to early AD pathology. However, analyzing free AGEs in the body fluids of AD patients has led to controversial results. Thus, this pilot study aimed to test the feasibility of detecting, identifying and quantifying differentially glycated, AGE or oxidatively modified peptides in CSF proteins of AD patients (n = 5) compared to a control group (n = 5). Methods: To this end, we utilized a data-dependent (DDA) nano liquid chromatography (LC) linear ion trap-Orbitrap tandem mass spectrometry (MS/MS) ) approach and database search that included over 30 glycative and oxidative modifications in four search nodes to analyze endogenous modifications on individual peptides. Furthermore, we quantified candidate peptide abundance using LC Quan. Results: We identified 299 sites of early and advanced glycation and 53 sites of oxidatively modified tryptophan. From those, we identified 17 promising candidates as putative biomarkers (receiver operating curve-area under the curve (ROC-AUC) > 0.8), albeit without statistical significance. Conclusions: The potential candidates with higher discrimination power showed correlations with established diagnostic markers, thus hinting toward the potential of those peptides as biomarkers.

Subjective and objective markers are important in describing healthy aging, yet little is known about their relationships. This study analysed the time-dependent association of dehydroepiandrosterone sulfate (DHEAS) with subjective health. At baseline, DHEAS was measured in participants aged 45–83 randomly selected from the general population. Subjective mental and physical health were assessed using the 12-item Short Form (SF-12) questionnaire at baseline and two follow-ups. In sex-specific linear regression models controlled for age, weight, tobacco consumption, Charlson Comorbidity Index, depression, and testosterone levels, the associations of DHEAS with the subscores of the SF-12 were analysed. DHEAS showed a positive cross-sectional association with subjective physical health, which was stronger in women and remained relevant after multivariable adjustment. However, longitudinal analyses revealed no long-term effect of DHEAS on subjective health. These findings suggest that the association between DHEAS and subjective physical health is temporary and that an underlying causality is unlikely.