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      Long-term development of lens fluorescence in a twin cohort: Heritability and effects of age and lifestyle

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          Abstract

          The blue-green autofluorescence of the ocular lens increases with age, glycemia and smoking, as the irreplaceable structural proteins of the lens slowly accumulate damage from the encounter with reactive molecular species. We have conducted a prospective study of lens autofluorescence over two decades in a twin cohort. The study included 131 phakic, non-diabetic adult twins (median age at follow-up 58 years, range 41–66 years) who were examined twice at an interval of 21 years. Change in anterior lens peak autofluorescence was analyzed in relation to age, current and baseline glycemia, cumulative smoking and heritability. The level of lens autofluorescence in the study population increased as a function of age and smoking (p ≤.002), but not as a function of glycemia (p ≥.069). Lens autofluorescence remained a highly heritable trait (90.6% at baseline and 93.3% at follow-up), but whereas the combined effect of age and cumulative smoking explained 57.2% of the variance in lens autofluorescence at baseline in mid-life, it only accounted for 31.6% at follow-up 21 years later. From mid to late adulthood, the level of blue-green fluorescence remained overwhelmingly heritable, but became less predictable from age, smoking habits and glycemic status. Presumably, as the lens ages, its intrinsic characteristics come to dominate over environmental and systemic factors, perhaps in a prelude to the development of cataract.

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          Advanced glycation end-products: a review.

          Advanced glycation end-products are a complex and heterogeneous group of compounds that have been implicated in diabetes related complications. At present it is not known if they are the cause or the consequence of the complications observed. We discuss the chemistry of advanced glycated end-product formation and their patho-biochemistry particularly in relation to the diabetic microvascular complications of retinopathy, neuropathy and nephropathy as well as their role in the accelerated vasculopathy observed in diabetes. The concept of carbonyl stress as a cause for advanced glycated end-product toxicity is mentioned. We discuss alterations in the concentrations of advanced glycated end-products in the body, particularly in relation to changes occurring with age, diabetes and its complications such as nephropathy. Problems relating to current methods of advanced glycated end-product detection and measurement are highlighted including the lack of a universally established method of detection or unit of measurement. Agents used for the treatment of advanced glycated end-product accumulation are reviewed, with an emphasis on the results of the recent phase III trials using aminoguanidine and diabetes related complications.
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            Advanced glycation end products in foods and a practical guide to their reduction in the diet.

            Modern diets are largely heat-processed and as a result contain high levels of advanced glycation end products (AGEs). Dietary advanced glycation end products (dAGEs) are known to contribute to increased oxidant stress and inflammation, which are linked to the recent epidemics of diabetes and cardiovascular disease. This report significantly expands the available dAGE database, validates the dAGE testing methodology, compares cooking procedures and inhibitory agents on new dAGE formation, and introduces practical approaches for reducing dAGE consumption in daily life. Based on the findings, dry heat promotes new dAGE formation by >10- to 100-fold above the uncooked state across food categories. Animal-derived foods that are high in fat and protein are generally AGE-rich and prone to new AGE formation during cooking. In contrast, carbohydrate-rich foods such as vegetables, fruits, whole grains, and milk contain relatively few AGEs, even after cooking. The formation of new dAGEs during cooking was prevented by the AGE inhibitory compound aminoguanidine and significantly reduced by cooking with moist heat, using shorter cooking times, cooking at lower temperatures, and by use of acidic ingredients such as lemon juice or vinegar. The new dAGE database provides a valuable instrument for estimating dAGE intake and for guiding food choices to reduce dAGE intake. 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.
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              Genetics of type 2 diabetes.

              Omar Ali (2013)
              Type 2 diabetes (T2D) is the result of interaction between environmental factors and a strong hereditary component. We review the heritability of T2D as well as the history of genetic and genomic research in this area. Very few T2D risk genes were identified using candidate gene and linkage-based studies, but the advent of genome-wide association studies has led to the identification of multiple genes, including several that were not previously known to play any role in T2D. Highly replicated genes, for example TCF7L2, KCNQ1 and KCNJ11, are discussed in greater detail. Taken together, the genetic loci discovered to date explain only a small proportion of the observed heritability. We discuss possible explanations for this "missing heritability", including the role of rare variants, gene-environment interactions and epigenetics. The clinical utility of current findings and avenues of future research are also discussed.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Project administrationRole: ResourcesRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Project administrationRole: ResourcesRole: Supervision
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                26 May 2022
                2022
                : 17
                : 5
                : e0268458
                Affiliations
                [1 ] Department of Ophthalmology, Rigshospitalet, Glostrup, Denmark
                [2 ] Department of Ophthalmology, Odense University Hospital, Odense, Denmark
                [3 ] Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
                [4 ] Department of Clinical Sciences, Ophthalmology in Malmö, Lund University, Malmö, Sweden
                [5 ] University Hospital Basel, Basel, Switzerland
                Girne American University - Karmi Campus: Girne Amerikan Universitesi, CYPRUS
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-6620-6242
                https://orcid.org/0000-0003-4061-9361
                https://orcid.org/0000-0002-9375-1510
                https://orcid.org/0000-0002-8549-8885
                Article
                PONE-D-21-26942
                10.1371/journal.pone.0268458
                9135443
                35617652
                7567cbc1-4ad1-4b92-bcad-3052d39b4d1f
                © 2022 Bjerager et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 August 2021
                : 30 April 2022
                Page count
                Figures: 2, Tables: 3, Pages: 12
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100008397, Velux Fonden;
                Award ID: 00028975
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100005111, Rigshospitalet;
                Award ID: E-23334-02
                Award Recipient :
                Funded by: P. Carl Petersens Fond
                Award ID: 19102
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100005860, Helsefonden;
                Award ID: 19-B-0063
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003035, Aase og Ejnar Danielsens Fond;
                Award ID: 18-10-0698
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100009898, Beckett-Fonden;
                Award ID: 19-2-3490
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100010347, Fabrikant Einar Willumsens Mindelegat;
                Award ID: 500028
                Award Recipient :
                This work was supported by THE VELUX FOUNDATIONS (Author JB, grant no. 00028975, https://veluxfoundations.dk/en), Rigshospitalets Forskningsudvalg (Author MB, grant no. E-23334-02, https://www.rigshospitalet.dk/forskning/om-forskningen/Sider/forskningsudvalget.aspx), P. Carl Petersens Fond (MB, grant no. 19102, https://www.pcarlp-fond.dk/), Helsefonden (MB, grant no. 19-B-0063, https://helsefonden.dk/), Aase og Ejnar Danielsens Fond (MB, grant no. 18-10-0698, https://danielsensfond.dk/), Beckett Fonden (MB, grant no. 19-2-3490, https://beckett-fonden.dk/) and Einar Willumsens Mindelegat (MB, grant no. 500028, https://www.legatbogen.dk/fabrikant-einar-willumsens-mindelegat/stoetteomraade/7684). The study was supported by the European Union under H2020-EU.2.1.1. - INDUSTRIAL LEADERSHIP - Leadership in enabling and industrial technologies - Information and Communication Technologies (ICT) (project ID 780989 MERLIN) ( https://cordis.europa.eu/project/rcn/213189_en.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Ocular System
                Ocular Anatomy
                Eye Lens
                Medicine and Health Sciences
                Anatomy
                Ocular System
                Ocular Anatomy
                Eye Lens
                Biology and Life Sciences
                Genetics
                Heredity
                Biology and Life Sciences
                Developmental Biology
                Twins
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Medical Conditions
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Medical Conditions
                Eye Diseases
                Lens Disorders
                Cataracts
                Medicine and Health Sciences
                Ophthalmology
                Eye Diseases
                Lens Disorders
                Cataracts
                Biology and Life Sciences
                Psychology
                Behavior
                Habits
                Smoking Habits
                Social Sciences
                Psychology
                Behavior
                Habits
                Smoking Habits
                Physical Sciences
                Physics
                Electromagnetic Radiation
                Luminescence
                Fluorescence
                Biology and Life Sciences
                Anatomy
                Head
                Eyes
                Medicine and Health Sciences
                Anatomy
                Head
                Eyes
                Biology and Life Sciences
                Anatomy
                Ocular System
                Eyes
                Medicine and Health Sciences
                Anatomy
                Ocular System
                Eyes
                Custom metadata
                All relevant data are available on Dryad: https://doi.org/10.5061/dryad.mcvdnck22.

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