Wrinkles and sagging skin—just normal aging, or can you blame your sweet tooth? We dive into “sugar sag,” exploring how sugar, processed foods, and even your crispy breakfast toast might be making you look older than if you’d said no to chocolate cake and yes to broccoli. Along the way, we encounter statistical adjustment, training and test data sets, what we call “references to nowhere,” plus some cadavers and collagen. Ever heard of an AGE reader? Find out how this tool might offer a sneak peek at your date’s age—and maybe even a clue about his… um… “performance.”Statistical topics <ul><li>Training and test sets</li><li>Statistical adjustment</li><li>Overfitting </li><li>Plagiarism</li><li>Proper citing practices</li><li>References to nowhere</li></ul>Methodologic morals<ul><li>“When you plagiarize, you steal the errors too.”</li><li>“Overdone statistical adjustment is like overdone photo filters–at a certain point it’s just laughable.”</li></ul>CitationsCollagen turnover: <ul><li>Verzijl N, DeGroot J, Thorpe SR, et al.<a href="https://www.jbc.org/article/S0021-9258(19)55828-8/fulltext">Effect of Collagen Turnover on the Accumulation of Advanced Glycation End Products</a>. JBC. 2000;275:39027-31.</li></ul>Cadaver study:<ul><li>Hamlin CR, Kohn RR, Luschin JH. <a href="https://diabetesjournals.org/diabetes/article/24/10/902/4787/Apparent-Accelerated-Aging-of-Human-Collagen-in">Apparent Accelerated Aging of Human Collagen in Diabetes Mellitus</a>. Diabetes. 1975; 24: 902–904.</li></ul><a href="https://www.diagnoptics.com/age-reader/">AGE Reader</a>Studies of AGEs and diabetes and health:<ul><li>Monnier VM, Cerami A. <a href="https://www.science.org/doi/10.1126/science.6779377">Nonenzymatic browning in vivo: possible process for aging of long-lived proteins</a>. Science. 1981;211:491-3. </li><li>Brownlee M, Vlassara H, Cerami A. <a href="https://www.acpjournals.org/doi/10.7326/0003-4819-101-4-527">Nonenzymatic glycosylation and the pathogenesis of diabetic complications</a>. Ann Intern Med. 1984;101:527-37. </li><li>Monnier VM, Vishwanath V, Frank KE, et al. <a href="https://www.nejm.org/doi/10.1056/NEJM198602133140702">Relation between Complications of Type I Diabetes Mellitus and Collagen-Linked Fluorescence</a>. N Engl J Med. 1986;314:403-408.</li><li>Monnier VM, Sell DR, Abdul-Karim FW, et al. <a href="https://diabetesjournals.org/diabetes/article/37/7/867/9388/Collagen-Browning-and-Cross-Linking-Are-Increased">Collagen browning and cross-linking are increased in chronic experimental hyperglycemia</a>. Relevance to diabetes and aging. Diabetes. 1988;37:867-72. </li><li>Monnier VM, Bautista O, Kenny D, et al. <a href="https://diabetesjournals.org/diabetes/article/48/4/870/10667/Skin-collagen-glycation-glycoxidation-and">Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications</a>. Diabetes 1999; 48: 870–80.</li><li>Genuth S, Sun W, Cleary P, et al. <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC2622724/">Glycation and carboxymethyllysine levels in skin collagen predict the risk of future 10-year progression of diabetic retinopathy and nephropathy in the diabetes control and complications trial and epidemiology of diabetes interventions and complications participants with type 1 diabetes</a>. Diabetes. 2005;54:3103-11. </li><li>van Waateringe RP, Slagter SN, van Beek AP, et al. <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5450154/">Skin autofluorescence, a non-invasive biomarker for advanced glycation end products, is associated with the metabolic syndrome and its individual components</a>. Diabetol Metab Syndr. 2017;9:42. </li><li>Kouidrat Y, Zaitouni A, Amad A, et al.<a href="https://linkinghub.elsevier.com/retrieve/pii/S1056-8727(16)30351-8"> Skin autofluorescence (a marker for advanced glycation end products) and erectile dysfunction in diabetes</a>. J Diabetes Complications. 2017;3:108-113. </li><li>Fujita N, Ishida M, Iwane T, et al. <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC10307664/">Association between Advanced Glycation End-Products, Carotenoids, and Severe Erectile Dysfunction</a>. World J Mens Health. 2023;41:701-11. </li><li>Uruska A, Gandecka A, Araszkiewicz A, et al. <a href="https://onlinelibrary.wiley.com/doi/10.1111/dme.13921">Accumulation of advanced glycation end products in the skin is accelerated in relation to insulin resistance in people with Type 1 diabetes mellitus</a>. Diabet Med. 2019;36:620-625. </li><li>Boersma HE, Smit AJ, Paterson AD, et al. <a href="https://www.nature.com/articles/s41598-024-71037-7">Skin autofluorescence and cause-specific mortality in a population-based cohort</a>. Sci Rep 2024;14:19967.</li></ul>Review article with conflicts of interest: <ul><li>Draelos ZD. <a href="https://jddonline.com/articles/individual-article-sugar-sag-what-is-skin-glycation-and-how-do-you-combat-it-S1545961624SSF378083s5X">Sugar Sag: What Is Skin Glycation and How Do You Combat It?</a> J Drugs Dermatol. 2024; 23:s5-10.</li></ul>Clinical study on AGE interrupter cream:<ul><li>Draelos ZD, Yatskayer M, Raab S, Oresajo C. <a href="https://onlinelibrary.wiley.com/doi/10.1111/j.1473-2165.2009.00428.x">An evaluation of the effect of a topical product containing C-xyloside and blueberry extract on the appearance of type II diabetic skin</a>. J Cosmet Dermatol. 2009;8:147-51. </li></ul>The citation trail:<ul><li>2023 review article: Zgutka K, Tkacz M, Tomasiak, et al.<a href="https://www.mdpi.com/1422-0067/24/12/9881"> A Role for Advanced Glycation End Products in Molecular Ageing</a>. Int J Mol Sci. 2023; 24: 9881. Sentence: “Interestingly, strict control of blood sugar for 4 months reduced the production of glycosylated collagen by 25%, and low-sugar food prepared by boiling could also reduce the production of AGEs [152].”</li><li>Reference 152 is a review article: Cao C, Xiao Z, Wu Y, et al. <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7146365/">Diet and Skin Aging-From the Perspective of Food Nutrition</a>. Nutrients. 2020;12:870. Sentence: “However, strict control of blood sugar for four months can reduce the production of glycosylated collagen by 25%, and low-sugar food prepared by boiling can also reduce the production of AGEs [93–95].”</li><li>Reference 93 is a review article: Nguyen HP, Katta R. <a href="https://www.skintherapyletter.com/aging-skin/glycation/">Sugar sag: Glycation and the role of diet in aging skin</a>. Skin Ther Lett. 2015; 20: 1–5. Sentence: “Tight glycemic control over a 4-month period can result in a reduction of glycated collagen formation by 25%.37,38”</li><li>Reference 94 and 38 is a review article: Draelos ZD. <a href="https://linkinghub.elsevier.com/retrieve/pii/S0738-081X(13)00072-2">Aging skin: the role of diet: facts and controversies</a>. Clin Dermatol. 2013;31:701-6. Sentence: “Tighter glycemic control can reduce glycated collagen by 25% in 4 months.” No citation given.</li><li>Reference 95 and 37 is a review article: Danby FW. <a href="https://linkinghub.elsevier.com/retrieve/pii/S0738-081X(10)00042-8">Nutrition and aging skin: Sugar and glycation</a>. Clin. Dermatol. 2010;28: 409–11. Sentence: “...tight glycemic control can drop glycated collagen formation by 25% in 4 months.” No citation given.</li><li>The origi...</li></ul>

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