Abstract
Population aging continues all over the world. Kidney aging is a major factor in the development and progression of chronic kidney disease (CKD), which shows premature phenotypic changes. Kidney aging associated with a decline in kidney function affects the functions of remote organs (heart, blood vessels, and brain), and CKD is a significant risk factor in cardiovascular disease (CVD) and stroke, both of which are age-related diseases. This association strongly indicates that kidney aging accelerates the aging of remote organs and that the kidney is a central organ in the maintenance of life.
Recent studies of the pathophysiology of CKD emphasize the contribution of endoplasmic reticulum (ER) stress and the link between ER stress and other pathogenic stresses such as oxidative stress and glycative stress, both of which are known to lead to premature aging. In particular, uremic toxins have received attention as causal factors of a vicious cycle of these stress signals, resulting in progression of CKD, rather than being a consequence of CKD. This article summarizes the impact and pathophysiological significance of oxidative stress and glycative stress, and ER stress. It also discusses the crosstalk of these stresses, novel evidence regarding uremic toxins as inducers of these stresses, and finally the contribution of these stresses to kidney premature aging.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adijiang A, Shimizu H, Higuchi Y, Nishijima F, Niwa T (2011) Indoxyl sulfate reduces klotho expression and promotes senescence in the kidneys of hypertensive rats. J Ren Nutr 21:105–109
Chen Y, Liu CP, Xu KF, Mao XD, Lu YB, Fang L, Yang JW, Liu C (2008) Effect of taurine-conjugated ursodeoxycholic acid on endoplasmic reticulum stress and apoptosis induced by advanced glycation end products in cultured mouse podocytes. Am J Nephrol 28:1014–1022
Dong Y, Zhang M, Wang S, Liang B, Zhao Z, Liu C, Wu M, Choi HC, Lyons TJ, Zou MH (2010) Activation of AMP-activated protein kinase inhibits oxidized LDL-triggered endoplasmic reticulum stress in vivo. Diabetes 59:1386–1396
Hasnain SZ, Borg DJ, Harcourt BE, Tong H, Sheng YH, Ng CP, Das I, Wang R, Chen AC, Loudovaris T, Kay TW, Thomas HE, Whitehead JP, Forbes JM, Prins JB, McGuckin MA (2014) Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress. Nat Med 20:1417–1426
Ikeda Y, Inagi R, Miyata T, Nagai R, Arai M, Miyashita M, Itokawa M, Fujita T, Nangaku M (2011) Glyoxalase I retards renal senescence. Am J Pathol 179:2810–2821
Inagi R (2010) Endoplasmic reticulum stress as a progression factor for kidney injury. Curr Opin Pharmacol 10:156–165
Inagi R (2011) Inhibitors of advanced glycation and endoplasmic reticulum stress. Methods Enzymol 491:361–380
Inagi R, Ishimoto Y, Nangaku M (2014) Proteostasis in endoplasmic reticulum – new mechanisms in kidney disease. Nat Rev Nephrol 10:369–378
Jo-Watanabe A, Ohse T, Nishimatsu H, Takahashi M, Ikeda Y, Wada T, Shirakawa J, Nagai R, Miyata T, Nagano T, Hirata Y, Inagi R, Nangaku M (2014) Glyoxalase I reduces glycative and oxidative stress and prevents age-related endothelial dysfunction through modulation of endothelial nitric oxide synthase phosphorylation. Aging Cell 13:519–528
Jurk D, Wilson C, Passos JF, Oakley F, Correia-Melo C, Greaves L, Saretzki G, Fox C, Lawless C, Anderson R, Hewitt G, Pender SL, Fullard N, Nelson G, Mann J, van de Sluis B, Mann DA, von Zglinicki T (2014) Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Nat Commun 2:4172
Kizer JR, Benkeser D, Arnold AM, Ix JH, Mukamal KJ, Djousse L, Tracy RP, Siscovick DS, Psaty BM, Zieman SJ (2014) Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults. Atherosclerosis 235:116–121
Kooman JP, Kotanko P, Schols AM, Shiels PG, Stenvinkel P (2014) Chronic kidney disease and premature ageing. Nat Rev Nephrol 10:732–742
Kuro-O M (2011) A phosphate-centric paradigm for pathophysiology and therapy of chronic kidney disease. Kidney Int Suppl 3:420–426
Liu J, Huang K, Cai GY, Chen XM, Yang JR, Lin LR, Yang J, Huo BG, Zhan J, He YN (2014) Receptor for advanced glycation end-products promotes premature senescence of proximal tubular epithelial cells via activation of endoplasmic reticulum stress-dependent p21 signaling. Cell Signal 26:110–121
Loughlin DT, Artlett CM (2011) Modification of collagen by 3-deoxyglucosone alters wound healing through differential regulation of p38 MAP kinase. PLoS One 6:e18676
Palm F, Nangaku M, Fasching A, Tanaka T, Nordquist L, Hansell P, Kawakami T, Nishijima F, Fujita T (2010) Uremia induces abnormal oxygen consumption in tubules and aggravates chronic hypoxia of the kidney via oxidative stress. Am J Physiol Renal Physiol 299:F380–F386
Pérez VI, Bokov A, Remmen HV, Mele J, Ran Q, Ikeno Y, Richardson A (2009a) Is the oxidative stress theory of aging dead? Biochim Biophys Acta 1790:1005–1014
Pérez VI, Van Remmen H, Bokov A, Epstein CJ, Vijg J, Richardson A (2009b) The overexpression of major antioxidant enzymes does not extend the lifespan of mice. Aging Cell 8:73–75
Rabbani N, Thornalley PJ (2011) Glyoxalase in diabetes, obesity and related disorders. Semin Cell Dev Biol 22:309–317
Shanahan CM (2013) Mechanisms of vascular calcification in CKD-evidence for premature ageing? Nat Rev Nephrol 9:661–670
Shimizu H, Yisireyili M, Nishijima F, Niwa T (2012) Stat3 contributes to indoxyl sulfate-induced inflammatory and fibrotic gene expression and cellular senescence. Am J Nephrol 36:184–189
Stenvinkel P, Larsson TE (2013) Chronic kidney disease: a clinical model of premature aging. Am J Kidney Dis 62:339–351
Tanaka T, Yamaguchi J, Higashijima Y, Nangaku M (2013) Indoxyl sulfate signals for rapid mRNA stabilization of Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) and suppresses the expression of hypoxia-inducible genes in experimental CKD and uremia. FASEB J 27:4059–4075
Uribarri J, Cai W, Peppa M, Goodman S, Ferrucci L, Striker G, Vlassara H (2007) Circulating glycotoxins and dietary advanced glycation endproducts: two links to inflammatory response, oxidative stress, and aging. J Gerontol A Biol Sci Med Sci 62:427–433
Walker SR, Wagner M, Tangri N (2014) Chronic kidney disease, frailty, and unsuccessful aging. J Ren Nutr 24:364–370
Wang M, Kaufman RJ (2014) The impact of the endoplasmic reticulum protein-folding environment on cancer development. Nat Rev Cancer 14:581–597
Wu J, Zhang R, Torreggiani M, Ting A, Xiong H, Striker GE, Vlassara H, Zheng F (2010) Induction of diabetes in aged C57B6 mice results in severe nephropathy: an association with oxidative stress, endoplasmic reticulum stress, and inflammation. Am J Pathol 176:2163–2176
Zhuang A, Forbes JM (2014) Stress in the kidney is the road to pERdition: is endoplasmic reticulum stress a pathogenic mediator of diabetic nephropathy? J Endocrinol 222:R97–R111
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Japan
About this chapter
Cite this chapter
Inagi, R. (2015). Oxidative Stress and Endoplasmic Reticulum Stress in Kidney Aging: Impact of Uremic Toxins as the Cause of Stress. In: Mori, N., Mook-Jung, I. (eds) Aging Mechanisms. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55763-0_12
Download citation
DOI: https://doi.org/10.1007/978-4-431-55763-0_12
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-55762-3
Online ISBN: 978-4-431-55763-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)