The accumulation of advanced glycation end products (AGEs) can contribute to kidney disease and renal failure. When AGEs accumulate in the filtering portions of kidneys, it reduces the ability to excrete waste.7
AGEs can lead to neurodegenerative diseases like Alzheimer’s and Parkinson’s because they contribute to the formation of cross-linked proteins. These damaged proteins accumulate in cells, disabling and eventually killing brain cells.8,9
When glycation occurs in the skin, it sensitizes the skin to ultraviolet (UV) radiation, triggering oxidative stress that damages DNA and increases the risk of skin cancers.10
AGEs damage joint cartilage, resulting in stiffening and loss of ability to handle stresses. AGEs are now recognized as major contributors to osteoarthritis.11
When similar AGE-related damage occurs in spinal discs, it can make disc injury and herniation (“slipped disc”) more likely.12
Glycation is especially damaging to our eyes. Not only does it lead to clouding of the lens (cataracts), it also causes retinal damage—both of which impair vision and ultimately produce blindness.13,14
The protein-rich walls of arteries, and even tiny capillaries, are especially vulnerable to glycation-induced damage.15 The resulting stiffening and inflammatory changes produce atherosclerosis, the cause of heart attacks, strokes, and other vascular disorders of aging.4
In short, glycation, linked to poor mitochondrial function, accelerates every aspect of human aging.
Humans’ dependence on energy derived from using sugar molecules and oxygen comes at a cost: toxic and reactive molecules interact with essential proteins and fats, damaging cells’ ability to function and accelerating their aging.
Glycation, the binding of sugar molecules to cellular structures, triggers massive inflammation and releases chemically stressful small molecules, which in turn damage mitochondria.
Mitochondria, our sole source of energy harvest from food, lose their efficiency and eventually fade away under this chemical onslaught.
The combination of glycation and mitochondrial dysfunction and loss rapidly accelerates aging, leading to chronic disorders that shorten life and reduce its quality.
Natural compounds have been identified that are capable of reversing this accelerated aging.
Benfotiamine, luteolin, pyridoxal-5-phosphate, and carnosine block glycation and prevent its destructive consequences.
PQQ, R-lipoic acid, and taurine enhance mitochondrial resistance to glycation-induced oxidative stress and promote formation of youthful new mitochondria.
This combination of nutrients can be expected to rejuvenate cellular energy levels while reducing chemically-induced damage to cells, thereby reversing the age-accelerating trend.
- Semba RD, Nicklett EJ, Ferrucci L. Does accumulation of advanced glycation end products contribute to the aging phenotype? J Gerontol A Biol Sci Med Sci. 2010;65(9):963-75.
- Yim MB, Yim HS, Lee C, et al. Protein glycation: creation of catalytic sites for free radical generation. Ann N Y Acad Sci. 2001;928:48-53.
- Krone CA, Ely JT. Ascorbic acid, glycation, glycohemoglobin and aging. Med Hypotheses. 2004;62(2):275-9.
- Ward MS, Fortheringham AK, Cooper ME, et al. Targeting advanced glycation endproducts and mitochondrial dysfunction in cardiovascular disease. Curr Opin Pharmacol. 2013;13(4):654-61.
- Hipkiss AR. Mitochondrial dysfunction, proteotoxicity, and aging: causes or effects, and the possible impact of NAD+-controlled protein glycation. Adv Clin Chem. 2010;50:123-50.
- Singh AK, Pandey SK, Saha G, et al. Pyrroloquinoline quinone (PQQ) producing Escherichia coli Nissle 1917 (EcN) alleviates age associated oxidative stress and hyperlipidemia, and improves mitochondrial function in ageing rats. Exp Gerontol. 2015;66:1-9.
- Fukami K, Yamagishi S, Ueda S, et al. Role of AGEs in diabetic nephropathy. Curr Pharm Des. 2008;14(10):946-52.
- Kikuchi S, Shinpo K, Takeuchi M, et al. Glycation–a sweet tempter for neuronal death. Brain Res Brain Res Rev. 2003;41(2-3):306-23.
- Hipkiss AR. Aging risk factors and Parkinson’s disease: contrasting roles of common dietary constituents. Neurobiol Aging. 2014;35(6):1469-72.
- Wondrak GT, Roberts MJ, Jacobson MK, et al. Photosensitized growth inhibition of cultured human skin cells: mechanism and suppression of oxidative stress from solar irradiation of glycated proteins. J Invest Dermatol. 2002;119(2):489-98.
- Verzijl N, DeGroot J, Ben ZC, et al. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis. Arthritis Rheum. 2002;46(1):114-23.
- Tsuru M, Nagata K, Jimi A, et al. Effect of AGEs on human disc herniation: intervertebral disc hernia is also effected by AGEs. Kurume Med J. 2002;49(1-2):7-13.
- Burd J, Lum S, Cahn F, et al. Simultaneous noninvasive clinical measurement of lens autofluorescence and rayleigh scattering using a fluorescence biomicroscope. J Diabetes Sci Technol. 2012;6(6):1251-9.
- Kessel L, Hougaard JL, Sander B, et al. Lens ageing as an indicator of tissue damage associated with smoking and non-enzymatic glycation–a twin study. Diabetologia. 2002;45(10):1457-62.
- Brown BE, Kim CH, Torpy FR, et al. Supplementation with carnosine decreases plasma triglycerides and modulates atherosclerotic plaque composition in diabetic apo E(-/-) mice. Atherosclerosis. 2014;232(2):403-9.
- Pomero F, Molinar Min A, La Selva M, et al. Benfotiamine is similar to thiamine in correcting endothelial cell defects induced by high glucose. Acta Diabetol. 2001;38(3):135-8.
- Schmid U, Stopper H, Heidland A, et al. Benfotiamine exhibits direct antioxidative capacity and prevents induction of DNA damage in vitro. Diabetes Metab Res Rev. 2008;24(5):371-7.
- Stirban A, Negrean M, Stratmann B, et al. Benfotiamine prevents macro-and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes. Diabetes Care. 2006;29(9):2064-71.
- Katare RG, Caporali A, Oikawa A, et al. Vitamin B1 analog benfotiamine prevents diabetes-induced diastolic dysfunction and heart failure through Akt/Pim-1-mediated survival pathway. Circ Heart Fail. 2010;3(2):294-305.
- Fraser DA, Hessvik NP, Nikolic N, et al. Benfotiamine increases glucose oxidation and downregulates NADPH oxidase 4 expression in cultured human myotubes exposed to both normal and high glucose concentrations. Genes Nutr. 2012;7(3):459-69.
- Tarallo S, Beltramo E, Berrone E, et al. Human pericyte-endothelial cell interactions in co-culture models mimicking the diabetic retinal microvascular environment. Acta Diabetol. 2012;49 Suppl 1:S141-51.
- Kihm LP, Muller-Krebs S, Klein J, et al. Benfotiamine protects against peritoneal and kidney damage in peritoneal dialysis. J Am Soc Nephrol. 2011;22(5):914-26.
- Balakumar P, Rohilla A, Krishan P, et al. The multifaceted therapeutic potential of benfotiamine. Pharmacol Res. 2010;61(6):482-8.
- Hammes HP, Du X, Edelstein D, et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med. 2003;9(3):294-9.
- Nakamura S, Niwa T. Pyridoxal phosphate and hepatocyte growth factor prevent dialysate-induced peritoneal damage. J Am Soc Nephrol. 2005;16(1):144-50.
- Lehman TD, Ortwerth BJ. Inhibitors of advanced glycation end product-associated protein cross-linking. Biochim Biophys Acta. 2001;1535(2):110-9.
- Khatami M, Suldan Z, David I, et al. Inhibitory effects of pyridoxal phosphate, ascorbate and aminoguanidine on nonenzymatic glycosylation. Life Sci. 1988;43(21):1725-31.
- Miyazawa T, Nakagawa K, Shimasaki S, et al. Lipid glycation and protein glycation in diabetes and atherosclerosis. Amino Acids. 2012;42(4):1163-70.
- Nakagawa K, Ibusuki D, Yamashita S, et al. Glycation of plasma lipoprotein lipid membrane and screening for lipid glycation inhibitor. Ann N Y Acad Sci. 2008;1126:288-90.
- Suzuki K, Nakagawa K, Miyazawa T. Augmentation of blood lipid glycation and lipid oxidation in diabetic patients. Clin Chem Lab Med. 2014;52(1):47-52.
- Harris GK, Qian Y, Leonard SS, et al. Luteolin and chrysin differentially inhibit cyclooxygenase-2 expression and scavenge reactive oxygen species but similarly inhibit prostaglandin-E2 formation in RAW 264.7 cells. J Nutr. 2006;136(6):1517-21.
- Deqiu Z, Kang L, Jiali Y, et al. Luteolin inhibits inflammatory response and improves insulin sensitivity in the endothelium. Biochimie. 2011;93(3):506-12.
- Kim JE, Son JE, Jang YJ, et al. Luteolin, a novel natural inhibitor of tumor progression locus 2 serine/threonine kinase, inhibits tumor necrosis factor-alpha-induced cyclooxygenase-2 expression in JB6 mouse epidermis cells. J Pharmacol Exp Ther. 2011;338(3):1013-22.
- Rezai-Zadeh K, Ehrhart J, Bai Y, et al. Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression. J Neuroinflammation. 2008;5:41.
- Chen CY, Peng WH, Tsai KD, et al. Luteolin suppresses inflammation-associated gene expression by blocking NF-kappaB and AP-1 activation pathway in mouse alveolar macrophages. Life Sci. 2007;81(23-24):1602-14.
- Zhu LH, Bi W, Qi RB, et al. Luteolin inhibits microglial inflammation and improves neuron survival against inflammation. Int J Neurosci. 2011;121(6):329-36.
- Gutierrez-Venegas G, Kawasaki-Cardenas P, Arroyo-Cruz SR, et al. Luteolin inhibits lipopolysaccharide actions on human gingival fibroblasts. Eur J Pharmacol. 2006;541(1-2):95-105.
- Chen HQ, Jin ZY, Wang XJ, et al. Luteolin protects dopaminergic neurons from inflammation-induced injury through inhibition of microglial activation. Neurosci Lett. 2008;448(2):175-9.
- Kim JS, Jobin C. The flavonoid luteolin prevents lipopolysaccharide-induced NF-kappaB signalling and gene expression by blocking IkappaB kinase activity in intestinal epithelial cells and bone-marrow derived dendritic cells. Immunology. 2005;115(3):375-87.
- Kotanidou A, Xagorari A, Bagli E, et al. Luteolin reduces lipopolysaccharide-induced lethal toxicity and expression of proinflammatory molecules in mice. Am J Respir Crit Care Med. 2002;165(6): 818-23.
- Reddy VP, Garrett MR, Perry G, et al. Carnosine: a versatile antioxidant and antiglycating agent. Sci Aging Knowledge Environ. 2005;2005(18):pe12.
- Hipkiss AR. Would carnosine or a carnivorous diet help suppress aging and associated pathologies? Ann N Y Acad Sci. 2006;1067:369-74.
- Cheng J, Wang F, Yu DF, et al. The cytotoxic mechanism of malondialdehyde and protective effect of carnosine via protein cross-linking/mitochondrial dysfunction/reactive oxygen species/MAPK pathway in neurons. Eur J Pharmacol. 2011;650(1):184-94.
- Baye E, Ukropcova B, Ukropec J, et al. Physiological and therapeutic effects of carnosine on cardiometabolic risk and disease. Amino Acids. 2016;48(5):1131-49.
- Hipkiss AR, Baye E, de Courten B. Carnosine and the processes of ageing. Maturitas. 2016;93:28-33.
- Hipkiss AR. Could carnosine or related structures suppress Alzheimer’s disease? J Alzheimers Dis. 2007;11(2):229-40.
- Babizhayev MA, Deyev AI, Yegorov YE. Olfactory dysfunction and cognitive impairment in age-related neurodegeneration: prevalence related to patient selection, diagnostic criteria and therapeutic treatment of aged clients receiving clinical neurology and community-based care. Curr Clin Pharmacol. 2011;6(4):236-59.
- Stegen S, Stegen B, Aldini G, et al. Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress. Appl Physiol Nutr Metab. 2015;40(9):868-76.
- Chowanadisai W, Bauerly KA, Tchaparian E, et al. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. J Biol Chem. 2010;285(1):142-52.
- Goraca A, Huk-Kolega H, Piechota A, et al. Lipoic acid – biological activity and therapeutic potential. Pharmacol Rep. 2011;63(4): 849-58.
- Morikawa T, Yasuno R, Wada H. Do mammalian cells synthesize lipoic acid? Identification of a mouse cDNA encoding a lipoic acid synthase located in mitochondria. FEBS Lett. 2001;498(1):16-21.
- Jiang T, Yin F, Yao J, et al. Lipoic acid restores age-associated impairment of brain energy metabolism through the modulation of Akt/JNK signaling and PGC1alpha transcriptional pathway. Aging Cell. 2013;12(6):1021-31.
- Suh JH, Moreau R, Heath SH, et al. Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Rep. 2005;10(1):52-60.
- Suh JH, Wang H, Liu RM, et al. (R)-alpha-lipoic acid reverses the age-related loss in GSH redox status in post-mitotic tissues: evidence for increased cysteine requirement for GSH synthesis. Arch Biochem Biophys. 2004;423(1):126-35.
- Suh JH, Shigeno ET, Morrow JD, et al. Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)-(alpha)-lipoic acid. FASEB J. 2001;15(3):700-6.
- Hagen TM, Vinarsky V, Wehr CM, et al. (R)-alpha-lipoic acid reverses the age-associated increase in susceptibility of hepatocytes to tert-butylhydroperoxide both in vitro and in vivo. Antioxid Redox Signal. 2000;2(3):473-83.
- Hagen TM, Ingersoll RT, Lykkesfeldt J, et al. (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB J. 1999;13(2):411-8.
- Liu J, Head E, Gharib AM, et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A. 2002;99(4):2356-61.
- Hansen SH, Birkedal H, Wibrand F, et al. Taurine and regulation of mitochondrial metabolism. Adv Exp Med Biol. 2015;803:397-405.
- Ripps H, Shen W. Review: taurine: a “very essential” amino acid. Mol Vis. 2012;18:2673-86.
- Froger N, Moutsimilli L, Cadetti L, et al. Taurine: the comeback of a neutraceutical in the prevention of retinal degenerations. Prog Retin Eye Res. 2014;41:44-63.
- De Luca A, Pierno S, Camerino DC. Taurine: the appeal of a safe amino acid for skeletal muscle disorders. J Transl Med. 2015;13:243.
- Ramila KC, Jong CJ, Pastukh V, et al. Role of protein phosphorylation in excitation-contraction coupling in taurine deficient hearts. Am J Physiol Heart Circ Physiol. 2015;308(3):H232-9.
- Gebara E, Udry F, Sultan S, et al. Taurine increases hippocampal neurogenesis in aging mice. Stem Cell Res. 2015;14(3):369-79.
- Militante J, Lombardini JB. Age-related retinal degeneration in animal models of aging: possible involvement of taurine deficiency and oxidative stress. Neurochem Res. 2004;29(1):151-60.
- Xu S, He M, Zhong M, et al. The neuroprotective effects of taurine against nickel by reducing oxidative stress and maintaining mitochondrial function in cortical neurons. Neurosci Lett. 2015;590: 52-7.
- Chou CT, Lin HT, Hwang PA, et al. Taurine resumed neuronal differentiation in arsenite-treated N2a cells through reducing oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction. Amino Acids. 2015;47(4):735-44.
- Vlassara H, Cai W, Tripp E, et al. Oral AGE restriction ameliorates insulin resistance in obese individuals with the metabolic syndrome: a randomised controlled trial. Diabetologia. 2016;59(10):2181-92.