Suchergebnisse

Scope: Diets with low content in advanced glycation end products (AGEs) lead to beneficial properties in highly prevalent age-related diseases. To shed light on the mechanisms behind, the changes induced by a low AGE dietary intervention in the circulating metabolome are analyzed. Methods and Results: To this end, 20 non-diabetic patients undergoing peritoneal dialysis are randomized to continue their usual diet or to one with a low content of AGEs for 1 month. Then, plasmatic metabolome and lipidomes are analyzed by liquid-chromatography coupled to mass spectrometry. The levels of defined AGE structures are also quantified by ELISA and by mass-spectrometry. The results show that the low AGE diet impinged significant changes in circulating metabolomes (166 molecules) and lipidomes (91 lipids). Metabolic targets of low-AGE intake include sphingolipid, ether-lipids, and glycerophospholipid metabolism. Further, it reproduces some of the plasma characteristics of healthy aging. Conclusion : The finding of common pathways induced by low-AGE diets with previous metabolic traits implicated in aging, insulin resistance, and obesity suggest the usefulness of the chosen approach and supports the potential extension of this study to other populations. ; The authors acknowledge funding from the Spanish Ministry of Economy and Competitiveness (PRX15/00613), Institute of Health Carlos III (P.I. 17–00134, PI20-00155) to M.P.-O.; and the Generalitat of Catalonia, Agency for Management of University and Research Grants (2017SGR696) to R.P. R.B. is a fellow from Program "Impuls"-Santander. R.R.-M. is a fellow from CONACYT. This study has been co-financed by FEDER funds from the European Union ("A way to build Europe"). M.J. is a professor under the "Serra Hunter" program (Generalitat de Catalunya).

Funding [WCRF 2015/1391, PI: M. Jenab] was obtained from Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant program. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de lEducation Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, the Catalan Institute of OncologyICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vaesterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (C864/A14136). V. Fedirko is supported by the Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award (Grant ID RR200056). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ; Advanced glycation end-products (AGEs) may promote oxidative stress and inflammation and have been linked to multiple chronic diseases, including cancer. However, the association of AGEs with mortality after colorectal cancer (CRC) diagnosis has not been previously investigated. Multivariable Cox proportional hazards models were used to calculate hazard ratios and corresponding 95% confidence intervals for associations between dietary intake of AGEs with CRC-specific and all-cause mortality among 5801 participant cases diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition study between 1993 and 2013. Dietary intakes of AGEs were estimated using country-specific dietary questionnaires, linked to an AGE database, that accounted for food preparation and processing. During a median of 58 months of follow-up, 2421 cases died (1841 from CRC). Individually or combined, dietary intakes of AGEs were not associated with all-cause and CRC-specific mortality among cases. However, there was a suggestion for a positive association between AGEs and all-cause or CRC-specific mortality among CRC cases without type II diabetes (all-cause, P-interaction = 0.05) and CRC cases with the longest follow-up between recruitment and cancer diagnosis (CRC-specific, P-interaction = 0.003; all-cause, P-interaction = 0.01). Our study suggests that pre-diagnostic dietary intakes of AGEs were not associated with CRC-specific or all-cause mortality among CRC patients. Further investigations using biomarkers of AGEs and stratifying by sex, diabetes status, and timing of exposure to AGEs are warranted. ; Wereld Kanker Onderzoek Fonds (WKOF), World Cancer Research Fund International grant program WCRF 2015/1391 ; World Health Organization ; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London ; Danish Cancer Society ; Ligue Contre le Cancer (France) Institut Gustave Roussy (France) Mutuelle Generale de lEducation Nationale (France) ; Institut National de la Sante et de la Recherche Medicale (Inserm) ; Deutsche Krebshilfe German Cancer Research Center (DKFZ) (Germany) German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany) ; Federal Ministry of Education & Research (BMBF) ; Fondazione AIRC per la ricerca sul cancro Compagnia di San Paolo Consiglio Nazionale delle Ricerche (CNR) ; Netherlands Government ; World Cancer Research Fund International (WCRF) ; Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) ; Junta de Andalucia Regional Government of Asturias (Spain) Regional Government of Basque Country (Spain) Regional Government of Murcia (Spain) Regional Government of Navarra (Spain) Catalan Institute of OncologyICO (Spain) ; Swedish Cancer Society Swedish Research Council County Council of Skane (Sweden) County Council of Vaesterbotten (Sweden) ; Cancer Research UK 14136 C8221/A29017 ; UK Research & Innovation (UKRI) Medical Research Council UK (MRC) 1000143 MR/M012190/1 UK Research & Innovation (UKRI) Medical Research Council UK (MRC) ; European Commission MR/N003284/1 MC-UU_12015/1 ; Cancer Research UK C864/A14136 ; Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award RR200056

Abstract
Skin autofluorescence (SAF), reflecting advanced glycation end-products' accumulation in tissue, has been proposed as a non-invasive aging biomarker. Yet, SAF has not been compared to well-established blood-based aging biomarkers such as MetaboHealth in association with frailty. Furthermore, no previous study determined the longitudinal association of SAF with frailty.
We used 2382 Doetinchem Cohort Study participants' (aged 46.0 to 85.4) cross-sectional data, of whom 1654 had longitudinal SAF measurements. SAF was measured using the AGE reader™. MetaboHealth was calculated on 1H-NMR-metabolomics. Linear regressions were used for the associations of SAF and MetaboHealth on the 36-deficit frailty index and logistic regressions for being pre-frail or frail as determined by the frailty phenotype. Longitudinal associations were determined by an interaction term between age and SAF in a linear mixed model.
SAF and MetaboHealth were associated with higher odds of pre-frailty (odd ratios per standard deviation SAF: 1.21(1.10;1.32), MetaboHealth: 1.35(1.24;1.49)) and frailty (SAF: 1.70(1.41;2.06), MetaboHealth: 1.90(1.57;2.32)). When mutually adjusted, both aging biomarkers remained associated with pre-frailty (SAF: 1.16(1.05;1.27), MetaboHealth 1.33(1.21;1.46)) and frailty (SAF: 1.52(1.25;1.85), MetaboHealth: 1.75(1.43;2.14)). Additionally, SAF and MetaboHealth were associated with higher frailty index scores (percentage increase per standard deviation SAF:1.35(1.00;1.70), MetaboHealth: 1.87(1.54;2.20)), also after mutual adjustment (SAF: 1.02(0.68;1.37), MetaboHealth: 1.69(1.35;2.02)). SAF was also longitudinally associated with the frailty index (percentage per unit/year increase 0.12(0.07;0.16)).
The mutual independence of SAF and MetaboHealth implies they capture distinct aspects of the aging process. Altogether, these findings emphasize SAF's clinical potential as an age-related decline biomarker, which could be further enhanced when combined with MetaboHealth.

This work was supported by grants from the Lleida Provincial Council, Renal Foundation Jaume Arnó, Instituto de Salud Carlos III (ISCIII, PI 12/00803 and PI 15/00260) and European Union [European Regional Development Fund (Fondo Europeo de Desarrollo Regional, Una manera de hacer Europa)]. CIBER de Diabetes y Enfermedades Metabólicas Asociadas and CIBER de Enfermedades Respiratorias are initiatives of the Instituto Carlos III. These funders had no role in the study design, data collection or analysis, the decision to publish or preparation of the manuscript. Also, the authors would like to thank Eva Castro, Virtudes María, Teresa Molí, Teresa Vidal, Cristina Dominguez, Marta Elias, Núria Sans and Meritxell Soria for their efforts in the accurate development of the ILERVAS project.

Annotation Dietary fibre technology is a sophisticated component of the food industry. This highly practical book presents the state-of-the-art and explains how the background science translates into commercial reality. An international team of experts has been assembled to offer both a global perspective and the nuts and bolts information relevant to those working in the commercial world. Coverage includes specific dietary fibre components (with overviews of chemistry, analysis and regulatory aspects of all key dietary fibres); measurement of dietary fibre and dietary fibre components (in-vitro and in-vivo); general aspects (eg chemical and physical nature; rheology and functionality; nutrition and health; and technological) and current hot topics. Ideal as an up-to-date overview of the field for food technologists; nutritionists and quality assurance and production managers.

The nonenzymatic adduction of malondialdehyde (MDA) to the protein amino groups leads to the formation of malondialdehyde-lysine (MDALys). The degree of unsaturation of biological membranes and the intracellular oxidative conditions are the main factors that modulate MDALys formation. The low concentration of this modification in the different cellular components, found in a wide diversity of tissues and animal species, is indicative of the presence of a complex network of cellular protection mechanisms that avoid its cytotoxic effects. In this review, we will focus on the chemistry of this lipoxidation-derived protein modification, the specificity of MDALys formation in proteins, the methodology used for its detection and quantification, the MDA-lipoxidized proteome, the metabolism of MDA-modified proteins, and the detrimental effects of this protein modification. We also propose that MDALys is an indicator of the rate of aging based on findings which demonstrate that (i) MDALys accumulates in tissues with age, (ii) the lower the concentration of MDALys the greater the longevity of the animal species, and (iii) its concentration is attenuated by anti-aging nutritional and pharmacological interventions ; Research by the authors was supported by the Spanish Ministry of Economy and Competitiveness, Institute of Health Carlos III (FIS grants PI13/00584 and PI14/00328), the Spanish Ministry of Science, Innovation, and Universities (Ministerio de Ciencia, Innovación y Universidades, RTI2018-099200-BI00), and the Generalitat of Catalonia: Agency for Management of University and Research Grants (2017SGR696), and Department of Health (SLT002/16/00250) to RP. This study has been co-financed by FEDER funds from the European Union ("A way to build Europe"). IRBLleida is a CERCA Programme/Generalitat of Catalonia.