Renal senescence in 2008: Progress and challenges

International Urology and Nephrology

Volumn 40, Issue 3, 2008, Pages 823-839

  Zhou, Xin J ^a   Saxena, Ramesh ^a   Liu, Zhihong ^b   Vaziri, N D ^c   Silva, Fred G ^d  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b MEDICAL SCHOOL OF NANJING UNIVERSITY   (China)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d United States and Canadian Academy of Pathology   (United States)

Author keywords

Aging; Geriatric nephrology; Klotho; Oxidative stress; Renal pathology; Senescence; Telomeres

Indexed keywords

CALCIUM; ERYTHROPOIETIN; KLOTHO PROTEIN; POTASSIUM; VITAMIN D;

ACID BASE BALANCE; AGING; AUTOPHAGY; DISEASE COURSE; ELECTROLYTE DISTURBANCE; FUNCTIONAL GENOMICS; GENE EXPRESSION; GLOMERULOSCLEROSIS; GLOMERULUS FILTRATION RATE; HUMAN; KIDNEY BLOOD FLOW; KIDNEY DISEASE; KIDNEY FUNCTION; KIDNEY INTERSTITIUM; KIDNEY TUBULE; MITOCHONDRION; MORBIDITY; MORTALITY; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PATHOLOGICAL ANATOMY; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SENESCENCE; TELOMERE; URINE ACIDIFICATION;

ACID-BASE EQUILIBRIUM; AGING; GLUCURONIDASE; HUMANS; KIDNEY; OXIDATIVE STRESS; TELOMERE; WATER-ELECTROLYTE BALANCE;

EID: 48549095189     PISSN: 03011623     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11255-008-9405-0     Document Type: Review

References (165)

1. US Census Bureau. International database. Table 094. Midyear population, by age and sex. Available at http://www.census.gov/population/www/ projections/natdet-D1A.html
2. Zhen JH, Li L, Zhou XJ (2008) The aging kidney and associated diseases. In: Li LS, Liu ZH (eds) Nephrology in China (in press)
3. Levit K, Smith C, Cowan C et al (2003) Trends in US health care spending, 2001. Health Aff 22:154-164
4. United States Renal Data System (2007) Annual data report. Bethesda, MD
5. Silva FG (2005) The aging kidney: A review - part I. Int Urol Nephrol 37:185-205
6. Silva FG (2005) The aging kidney: A review - part II. Int Urol Nephrol 37:419-432
7. Zhou XJ, Rakheja D, Yu XQ, Saxena R, Vaziri ND et al (2008) The aging kidney. Kidney Int (in press)
8. Gourtsoyiannis N, Prassopoulos P, Cavouras D et al (1990) The thickness of the renal parenchyma decreases with age: A CT study of 360 patients. Am J Roentgenol 155:541-544
9. McLachlan M, Wasserman P (1981) Changes in sizes and distensibility of the aging kidney. Br J Radiol 54:488-491
10. Nyengaard JR, Bendtsen TF (1992) Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat Rec 232(2):194-201
11. Hughson M, Farris AB 3rd, Douglas-Denton R et al (2003) Glomerular number and size in autopsy kidneys: The relationship to birth weight. Kidney Int 63(6):2113-2122
12. Newbold KM, Sandison A et al (1992) Comparison of size of juxtamedullary and outer cortical glomeruli in normal adult kidney. Virchows Arch A Pathol Anat Histopathol 420(2):127-129
13. Hughson MD, Douglas-Denton R et al (2006) Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States. Kidney Int 69(4):671-678
14. Kasiske BL (1987) Relationship between vascular disease and age-associated changes in the human kidney. Kidney Int 31:1153-1159
15. Smith SM, Hoy WE et al (1989) Low incidence of glomerulosclerosis in normal kidneys. Arch Pathol Lab Med 113(11):1253-1255
16. Kaplan C, Pasternack B, Shah H et al (1995) Age-related incidence of sclerotic glomeruli in human kidneys. Am J Pathol 80:227-234
17. Brenner BM (1983) Hemodynamically mediated glomerular injury and the progressive nature of kidney disease. Kidney Int 23(4):647-655
18. Hill GS, Heudes D et al (2003) Morphometric study of arterioles and glomeruli in the aging kidney suggests focal loss of autoregulation. Kidney Int 63(3):1027-1036
19. Samuel T, Hoy WE et al (2005) Determinants of glomerular volume in different cortical zones of the human kidney. J Am Soc Nephrol 16(10):3102-3109
20. Zhou XJ, Laszik ZG, Silva FG (2008)Anatomical changes in the aging kidney. In: Macias-Nunez JF, Cameron JS, Oreopoulos DG (eds) The aging kidney in health and disease. Springer, pp 39-54
21. Baert L, Steg A (1977) Is the diverticulum of the distal and collecting tubules a preliminary stage of the simple cyst in the adult? J Urol 118(5):707-710
22. Takazakura E, Sawabu N et al (1972) Intrarenal vascular changes with age and disease. Kidney Int 2(4):224-230
23. Tracy RE, Ishii T (2000) What is 'nephrosclerosis'? Lessons from the US, Japan, and Mexico. Nephrol Dial Transplant 15(9):1357-1366
24. Tracy RE (2007) Age trends of renal arteriolar hyalinization explored with the aid of serial sections. Nephron Clin Pract 105(4):c171-c177
25. Tracy RE, Newman WP III, Wattigney WA et al (1995) Histologic features of atherosclerosis and hypertension from autopsies of young individuals in a defined geographic population: The Bogalusa Heart Study. Atherosclerosis 116(2):163-179
26. Tracy RE, Parra D et al (2002) Influence of arteriolar hyalinization on arterial intimal fibroplasia in the renal cortex of subjects in the United States, Peru, and Bolivia, applicable also to other populations. Am J Hypertens 15(12):1064-1073
27. Tracy RE (1998) Histologic characteristics of coronary artery in relation to the renovasculopathies of hypertension. Ann Diagn Pathol 2(3):159-166
28. Fogo A, Breyer JA et al (1997) Accuracy of the diagnosis of hypertensive nephrosclerosis in African Americans: A report from the African American Study of Kidney Disease (AASK) Trial. AASK Pilot Study Investigators. Kidney Int 51(1):244-252
29. Wesson LG Jr (1969) Renal hemodynamlcs in physiological states. In: Physiology of the human kidney. Grune & Stratton, New York, pp 96-108
30. Hollenberg NK, Adams DF, Solomon HS et al (1974) Senescence and the renal vasculature in normal man. Circ Res 34:309-316
31. Ljungqvist A, Lagergren C (1962) Normal intrarenal arterial pattern in adult and aging human kidney. J Anat 96:285-300
32. Davidson AJ, Tamer LB, Downs WM (1969) A study of the angiographic appearance of the kidney In an aging normotensive population. Radiology 92:975-983
33. McLachlan MS, Guthrie JC, Anderson CK et al (1977) Vascular and glomerular changes in the aging kidney. J Pathol 121:65-78
34. Long DA, Mu W, Price KL et al (2005) Blood vessels and the aging kidney. Nephron Exp Nephrol 101:e95-e99
35. Kang DH, Anderson S, Kim YG et al (2001) Impaired angiogenesis in the aging kidney: Vascular endothelial growth factor and thrombospondin-1 in renal disease. Am J Kidney Dis 37:601-611
36. Long DA, Price KL, Mu W et al (2004) Angiopoietin-1, a vascular growth factor with a potentially novel role in aging (abstract). J Am Soc Nephrol 15:477A
37. Nichols WW, O'Rourke MF (2005) McDonald's blood flow in arteries: theoretical, experimental and clinical principles, 5th edn. Hodder Arnold
38. Virmani R, Avolio AP, Mergner WJ et al (1991) Effect of aging on aortic morphology in populations with high and low prevalence of hypertension and atherosclerosis. Am J Pathol 139:1119-1129
39. Boutouyrie P, Laurent S, Benetos A et al (1992) Opposing effects of aging on distal and proximal large arteries of hypertensives. J Hypertens 10(suppl 6):S87-S91
40. Laurent S, Cockcroft J, van Bortel L et al (2006) European network for non-invasive investigation of large arteries. Expert consensus document on arterial stiffness: Methodological issues and clinical applications. Eur Heart J 27:2588-2605
41. Donnan G, Yon R, Dewey H et al (1997) Important issues in stroke today. In: Hansson L, Birkenhager W (eds) Handbook of hypertension, vol 18. Elsevier, pp 268-81
42. Bakris G (2005) Proteinuria: A link to understanding changes in vascular compliance? Hypertension 14:196-209
43. Verhave JC, Fesler P, du Cailar G et al (2005) Elevated pulse pressure is associated with low renal function in elderly patients with isolated systolic hypertension. Hypertension 45:586-591
44. Lea J, Greene T, Hebert L et al (2005) The relationship between magnitude of proteinuria and reduction and risk of end-stage renal disease. Arch Intern Med 165:947-953
45. O'Rourke MF (2007) Arterial aging: Pathophygiological principles. Vasc Med 12:329-341
46. Fisher CM (1982) Lacunar strokes and infarcts: A review. Neurology 32:871-876
47. Cullen KM, Kocsi Z, Stone J (2005) Pericapillary haem-rich deposits: evidence for microhaemorrhages in aging human cerebral cortex. J Cereb Blood Flow Metab 25:1656-1667
48. Cullen KM, Kocsi Z, Stone J (2006) Microvascular pathology in the aging human brain: Evident that senile plaques are sites of microhemorrhages. Neurobiol Aging 27:1786-1796
49. Buee L, Hof PR, Delacourte A (1997) Brain microvascular changes in Alzheimer's disease and other dementias. Ann N Y Acad Sci 826:7-24
50. Willum-Hansen T, Staessen JA, Torp-Pederson C et al (2006) Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population. Circulation 113:664-670
51. Mattace-Raso FU, van der Cammen TJ, Hoffman A et al (2006) Arterial stiffness and risk of coronary heart disease and stroke: The Rotterdam study. Circulation 113:657-663
52. Meaume S, Benetos A, Henry OF et al (2001) Aortic pulse wave velocity predicts cardiovascular mortality in subjects, 70 years of age. Arterioscler Thromb Vasc Biol 21:2046-2050
53. Ibsen H, Olsen M, Wachtell K et al (2005) Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients. Hypertension 45:198-202
54. Sarnak MJ, Greene T, Wang X et al (2005) The effect of a lower target blood pressure on the progression of kidney disease: Long-term follow-up of the modification of diet in renal disease study. Ann Intern Med 142:342-351
55. Safar ME, London GM, Plante GE (2004) Arterial stiffness and kidney function. Hypertension 43:163-168
56. Williams B, Lacy PS, Thom SM et al (2006) Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: Principal results of the conduit artery function evaluation (CAFE) study. Circulation 113:1213-1225
57. Nichols W, O'Rourke M (2006) Principles of measurement, preventing and treating arterial stiffness In: Safar ME, O'Rourke MF (eds) Arterial stiffness, vol 23. Handbook of hypertension. Elsevier, pp 137-160, 503-516
58. Morrissey PE, Yango AF (2006) Renal transplantation: Older recipients and donors. Clin Geriatr Med 22(3):687-707
59. Lindeman RD, Tobin J et al (1985) Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 33(4):278-285
60. Shannon JA, Smith HW (1935) The excretion of insulin, xylose and urea by normal and phlorizinized man. J Clin Invest 14:393-404
61. Maher FT, Nolan NG, Elveback LR (1971) Comparison of simultaneous clearances of 125-I-labeled sodium iothalamate (Glofil) and of inulin. Mayo Clin Proc 46:690-691
62. Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31
63. Levey AS, Bosch JP, Lewis JB et al (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130:461
64. Wieczorowska-Tobis K, Niemir ZI et al (2006) Difference in estimated GFR with two different formulas in elderly individuals. Int Urol Nephrol 38:381-385
65. Berman N, Hostetter TH (2007) Comparing the Cockcroft Gault and MDRD equations for calculation of GFR and drug doses in the elderly. Nat Clin Pract Nephrol 3:644-645
66. Gill J, Malyuk R, Djurdjev O et al (2007) Use of GFR equations to adjust drug doses in an elderly multi-ethnic group' a cautionary tale. Nephrol Dial Transplant 22:2894-2899
67. Ognibene A, Mannucci E et al (2006) Cystatin C reference values and aging. Clin Biochem 39(6):658-661
68. Rowe JW, Shock NW, DeFronzo RA (1976) The influence of age on the renal response to water deprivation in man. Nephron 17:270-278
69. Tian Y, Serino R, Verbalis JG (2004) Downregulation of renal vasopressin V2 receptor and aquaporin-2 expression parallels age associated defects in urine concentration. Am J Physiol Renal Physiol 287:F797-F805
70. Combet S, Teillet L, Geelen G et al (2001) Food restriction prevents age-related polyuria by vasopressin-dependent recruitment of aquaporin-2. Am J Physiol Renal Physiol 281:F1123-F1131
71. Swenson KL, Sands JM, Jacobs JD et al (1997) Effects of aging on the vasopressin and aquaporin response to dehydration in Fischer 344/ Brown-Norway F1 rats. Am J Physiol Regul Integr Comp Physiol 273:R35-R47
72. Combat S, Geffroy N, Berthonaud V et al (2003) Correction of age related polyuria by dDAVP: Molecular analysis of aquaporins and urea transporters. Am J Physiol Renal Physiol 284:F199-F208
73. Bengele HH, Mathias RS, Perkins JH et al (1981) Urinary concentrating defect in the aged rat. Am J Physiol 240:F147-F150
74. Kbeinfebd M, Casimir M, Borra S (1979) Hyponatremia as observed in a chronic disease facility. J Am Geriatr Soc 27:156-161
75. Sunderam SG, Mankikar GD (1983) Hyponatraemia in the elderly. Age Aging 12:77-80
76. Adrogue HJ, Madias NE (2000) Hyponatremia. N Engl J Med 342:1581-1589
77. Ellison DH, Berl T (2007) The syndrome of inappropriate antidiuresis. N Engl J Med 356:2064-2072
78. Epstein M, Hollenberg NK (1976) Age as a determinant of renal sodium conservation in normal man. J Lab Clin Med 87:411-417
79. Weidmann P, Demyttenaere-Bursztein S, Maxwell MH et al (1975) Effect of aging on plasma renin and aldosterone in normal man. Kidney Int 8:325-333
80. Crane MG, Harris JJ (1976) Effect of aging on renin activity and aldosterone excretion. J Lab Clin Med 87:947-959
81. Shannon RP, Wei JY, Rosa RM et al (1986) The effect of age and sodium depletion on cardlovascubar response to orthostasis. Hypertension 8:438-443
82. Musso CG, Liakopoulos V et al (2006) Acute renal failure in the elderly: particular characteristics. Int Urol Nephrol 38:787-793
83. Luft FC, Grim CE, Fineberg N et al (1979) Effects of volume expansion and contraction in normotensive whites, blacks and subjects of different ages. Circulation 59:644-650
84. Luft FC, Weinberger MH, Fineberg NS et al (1987) Effects of age on renal sodium homeostasis and its relevance to sodium sensitivity. Am J Med 82(1B):9-15
85. Masilamani S, Zhang XZ, Baylis C (1998) Bluntedpressure natriuresis in the old rat: Participation of the renal nerves. Am J Kidney Dis 32(4):605-610
86. Baylis C (1993) Renal responses to acute angiotensin II inhibition and administered angiotensin II in the aging, conscious. chronically catheterized rat. Am J Kidney Dis 22:842-850
87. Luckey AE, Parsa CJ (2003) Fluid and electrolytes in the aged. Arch Surg 138:1055-1060
88. Musso CG, Gregori JAA, Macias-Nunez JF (2008) Renal handling of uric acid. magnesium, phosphorus, calcium and acid base in the elderly. In: Macias-Nunez JF, Cameron JS, Oreopoulos DG (eds) The aging kidney in health and disease. Springer, pp 155-171
89. Nakhoul F, Zmger C, Levin M, Gteen J, Winavet J, Better OS (1996) Urinary acidification capacity in the elderly. Prevalence of incomplete distal renal tubular acidosis in the healthy elderly. Geriat Nephrol Urol 5:149-155
90. Lindeman RD, Preuss HG (1994) Renal physiology and pathophysiology of aging. Geriat Nephrol Urol 4:113-120
91. Adler S, Lindeman RD, Yiengst SJ, Beard E, Shock NW (1968) Effect of acute acid loading on primary acid excretion by the aging human kidney. J Lab Clin Med 72:278-289
92. Agarwal BN, Cabebe FG (1980) Renal acidification in elderly subjects. Nephron 26:291-293
93. Hideo Y, Sacktor B, Kinsella J (1992) Age-associated changes in ammoniagenesis in isolated rat renal tubule segments. Am J Physiol 262(Renal Fluid Electrolyte Physiol 31):F600-F605
94. Frassetto LA, Morris RC Jr, Sebastian A (1996) Effect of age on blood acid-base composition in adult humans: Role of age-related renal functional decline. Am J Physiol 271(Renal Fluid Electrolyte Physiol. 40):F1114-F1122
95. Alpern RJ (1995) Trade-offs in the adaptation to acidosis. Kidney Int 47:1205-1215
96. Weidmann P, Demyttenaere-Bursztein S, Maxwell MH et al (1975) Effect of aging on plasma renin and aldosterone in normal man. Kidney Int 8:325-333
97. Noth RH, Lassman N, Tan SY et al (1977) Age and the renin-aldosterone system. Arch Int Med 137:1414-1417
98. Tsunoda K, Abe K, Goto T (1986) Effect of age on the reninangiotensin-aldosterone system in normal subjects: Simultaneous measurement of active and inactive renin, renin substrate and aldosterone in plasma. J Chin Endocrinol Metab 62:384-389
99. Annat G, Vinvent M, Tournlaire et al (1981) Relationship between blood pressure and plasma renin, aldosterone and dopammne-fJ-hydroxylase in the elderly. Gerontology 27:266-270
100. Weidman P, Beretta-Piccohl C, Ziegler WH et al (1978) Age versus urinary sodium for judging renin, aldosterone, and catecholamine levels: Studies in normal subjects and patients with essential hypertension. Kidney Int 14:619-628
101. Jung FF, Kennefick TM, Ingelfinger JR et al (1995) Down-regulation of the intrarenal renin-anglotensin system in the ageing rat. J Am Soc Nephrol 8:1573-1580
102. Skott P, Ingersbev J, Damkjaer Niebseon M et al (1987) The renin-angiotensin-aldosterone system in normal 85-year old people. Scand J Chin Lab Invest 47:6974
103. Musso C, Liakopoulos V et al (2006) Transtubular potassium concentration gradient: Comparison between healthy old people and chronic renal failure patients. Int Urol Nephrol 38:387-390
104. Eisenstaedt R, Penninx BW et al (2006) Anemia in the elderly: Current understanding and emerging concepts. Blood Rev 20:213-226
105. Ble A, Fink JC, Woodman RC et al (2005) Renal function, erythropoietin, and anemia of older persons: The InCHIANTI study. Arch Intern Med 165:2222-2227
106. Ershler WB, Sheng S et al (2005) Serum erythropoietin and aging: A longitudinal analysis. J Am Geriatr Soc 53:1360-1365
107. Carpenter MA, Kendall RG et al (1992) Reduced erythropoietin response to anaemia in elderly patients with normocytic anaemia. Eur J Haematol 49:119-121
108. Kario K, Matsuo T et al (1992) Reduced erythropoietin secretion in senile anemia. Am J Hematol 41:252-257
109. Ferrucci L, Guralnik JM et al (2007) Unexplained anaemia in older persons is characterised by low erythropoietin and low levels of pro-inflammatory markers. Br J Haematol 136:849-855
110. Dukas L, Schacht E et al (2005) In elderly men and women treated for osteoporosis a low creatinine clearance of <65 ml/min is a risk factor for falls and fractures. Osteoporos Int 16:1683-1690
111. Gallagher JC, Rapuri P, Smith L (2007) Falls are associated with decreased renal function and insufficient calcitriol production by the kidney. J Steroid Biochem Mol Biol 103:610-613
112. Arnaud CD, Sanchez SD (1990) The role of calcium in osteoporosis. Annu Rev Nutr 10:397-414
113. Mensenkamp AR, Hoenderop JGJ, Bindels RJM (2006) Recent advances in renal tubular calcium reabsorption. Current Opinion Nephrol Hypertension 15:524-529
114. Hoenderop JG, van der Kemp AW, Hartog A et al (1999) Molecular identification of the apical Ca2φ channel in 1, 25-dihydroxyvitamin D3-responsive epithelia. J Biol Chem 274:8375-8378
115. Clapham DE, Julius D, Montell C et al (2005) International union of pharmacology xlix nomenclature and structure-function relationships of transient receptor potential channels. Pharmacol Rev 57:427-450
116. Nilius B, Vennekens R, Prenen J et al (2000) Whole-cell and single channel monovalentcation currents through the novel rabbit epithelial Ca 2+ channel ECaC. J Physiol 527:239-248
117. van Abel M, Hoenderop JG, van der Kemp AW et al (2005) Coordinated control of renal Ca 2+ transport proteins by parathyroid hormone. Kidney Int 68:1708-1721
118. Hoenderop JG, Muller D, van der Kemp AW et al (2001) Calcitriol controls the epithelial calcium channel in kidney. J Am Soc Nephrol 12:1342-1349
119. Chang Q, Hoefs S, van der Kemp AW et al (2005) The beta-glucuronidase Klotho hydrolyzes and activates the TRPV5 channel. Science 310:490-493
120. Kuro-OM MatsumuraY, Aizawa H et al (1997) Mutation of the mouse Klotho geneleads to a syndrome resembling ageing. Nature 390:45-51
121. Jiang H, Ju Z, Rudolph KL (2007) Telomere shortening and ageing. Z Gerontol Geriat 40:314-324
122. Blackburn EH (2001) Switching and signaling at the telomere. Cell 106:661-673
123. Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25:585-621
124. Melk A, Ramassar V, Helms LM et al (2000) Telomere shortening in kidney with age. J Am Soc Nephrol 11:444-453
125. Hara E, Smith R, Parry D et al (1996) Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence. Mol Cell Biol 16:859-867
126. Chkhotua AB, Gabusi E, Altimari A et al (2003) Increased expression of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor genes in aging kidney and chronic allograft nephropathy. Am J Kidney Dis 41(6):1303-1313
127. Melk A, Schmidt BM, Takeuchi O et al (2004) Expression of p16INK4a and other cell cycle regulator and senescence-associated genes in aging human kidney. Kidney Int 65:510-520
128. Houben JMJ, Moonen HJJ, van Schooten FJ et al (2008) Telomere length assessment: Biomarker of chronic oxidative stress? Free Rad Biol Med 44(3):235-246
129. de Meyer T, Rietzschel ER, de Buyzere ML et al (2008) Studying telomeres in a longitudinal population based study. Front Biosci 13:2960-2970
130. Arking DE, Krebsova A, Macek M Sr et al (2002) Association of human aging with a functional variant of Klotho. Proc Natl Acad Sci USA 99:856-861
131. Arking DE, Becker DM, Yanek LR et al (2003) KLOTHO allele status and the risk of early-onset occult coronary artery disease. Am J Hum Genet 72:1154-1161
132. Arking DE, Atzmon G, Arking A et al (2005) Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity. Circ Res 96:412-418
133. Kawano K, Ogata N, Chiano M et al (2002) Klotho gene polymorphisms associated with bone density of aged postmenopausal women. J Bone Miner Res 17:1744-1751
134. Ogata N, Matsumura Y, Shiraki M et al (2002) Association of Klotho gene polymorphism with bone density and spondylosis of the lumbar spine in postmenopausal women. Bone 31:37-42
135. Yamada Y, Ando F, Niino N et al (2005) Association of polymorphisms of the androgen receptor and Klotho genes with bone mineral density in Japanese women. J Mol Med 83:50-57
136. Tohyama O, Imura A, Iwano A et al (2004) Klotho is a novel beta-glucuronidase capable of hydrolyzing steroid beta-glucuronides. J Biol Chem 279:9777-9784
137. Kurosu H, Yamamoto M, Clark JD et al (2005) Suppression of aging in mice by the hormone Klotho. Science 309:1829-1833
138. Kuro-o M (2008) Klotho as a regulator of oxidative stress and senescence. Biol Chem 389:233-241
139. Mitobe M, Yoshida T et al (2005) Oxidative stress decreases Klotho expression in a mouse kidney cell line. Nephron Exp Nephrol 101:e67-e74
140. Tsujikawa H, Kurotaki Y, Fujimori T et al (2003) Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Mol Endocrinol 17:2393-2403
141. Shimada T, Kakitani M, Yamazaki Y et al (2004) Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 113:561-568
142. Razzaque MS, Sitara D, Taguchi T et al (2006) Premature aging-like phenotype in fibroblast growth factor 23 null mice is a vitamin D-mediated process. FASEB J 20:720-722
143. Kurosu H, Ogawa Y, Miyoshi M et al (2006) Regulation of fibroblast growth factor-23 signaling by Klotho. J Biol Chem 281:6120-6123
144. Fu L, John LM, Adams SH et al (2004) Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes. Endocrinology 145:2594-2603
145. Kharitonenkov A, Shiyanova TL, Koester A et al (2005) FGF-21 as a novel metabolic regulator. J Clin Invest 115:1627-1635
146. Cassina P, Pehar M, Vargas MR et al (2005) Astrocyte activation by fibroblast growth factor-1 and motor neuron apoptosis: Implications for amyotrophic lateral sclerosis. J Neurochem 93:38-46
147. Saito K, Ishizaka N, Mitani H et al (2003) Iron chelation and free radical scavenger suppress angiotensin II-induced downregulation of Klotho, an anti-aging gene, in rat. FEBS Lett 551:58-62
148. Nagai R, Saito Y, Ohyama Y et al (2000) Endothelial dysfunction in the Klotho mouse and downregulation of Klotho gene expression in various animal models of vascular and metabolic diseases. Cell Mol Life Sci 57:738-746
149. Koh N, Fujimori T, Nishiguchi S et al (2001) Severely reduced production of Klotho in human chronic renal failure kidney. Biochem Biophys Res Commun 280:1015-1020
150. Mitani H, Ishizaka N, Aizawa T et al (2002) In vivo Klotho gene transfer ameliorates angiotensin II-induced renal damage. Hypertension 39:838
151. Mendoz-Nunez VM, Ruiz-Ramos M, Sanchez-Rodriguez MA et al (2007) Aging related oxidative stress in healthy humans. Tohoku J Exp Med 213:261-268
152. Jung T, Bader N, Grune T (2007) Lipofuscin: Formation, distribution and metabolic consequences. Ann N Y Acad Sci 1119:97-111
153. Melk A, Kittikowit W, Sandhu I et al (2003) Cell senescence in rat kidneys in vivo increases with growth and age despite lack of telomere shortening. Kidney Int 63:2134-2143
154. Frenkel-Denkberg G, Gershon D et al (1999) The function of hypoxia-inducible factor 1 (HIF-1) is impaired in senescent mice. FEBS Lett 462:341-344
155. Zou AP, Cowley AW Jr (2003) Reactive oxygen species and molecular regulation of renal oxygenation. Acta Physiol Scand 179:233-241
156. Buemi M, Nostro L et al (2005) Kidney aging: From phenotype to genetics. Rejuvenation Res 8:101-109
157. Reckelhoff JF, Kanji V et al (1998) Vitamin E ameliorates enhanced renal lipid peroxidation and accumulation of F2-isoprostanes in aging kidneys. Am J Physiol 274:R767-R774
158. Verbeke P, Perichon M et al (2000) Inhibition of nitric oxide synthase activity by early and advanced glycation end products in cultured rabbit proximal tubular epithelial cells. Biochim Biophys Acta 1502:481-494
159. Thomas SE, Anderson S et al (1998) Tubulointerstitial disease in aging: evidence for underlying peritubular capillary damage, a potential role for renal ischemia. J Am Soc Nephrol 9:231-242
160. Basso N, Paglia N et al (2005) Protective effect of the inhibition of the renin-angiotensin system on aging. Regul Pept 128:247-252
161. Zhou XJ, Vaziri ND, Zhang J et al (2002) Association of renal injury with nitric oxide deficiency in aged SHR: Prevention by hypertension control with AT1 blockade. Kidney Int 62:914-921
162. de Cavanagh EM, Piotrkowski B et al (2003) Enalapril and losartan attenuate mitochondrial dysfunction in aged rats. Faseb J 17:1096-1098
163. Huang C, Li J, Ke Q et al (2002) Ultraviolet-induced phosphorylation of p70(S6 K) at Thr(389) and Thr(421)/Ser(424) involves hydrogen peroxide and mammalian target of rapamycin but not Akt and atypical protein kinase C. Cancer Res 62:5689-5697
164. Blagosklonny MV (2007) Program-like aging and mitochondria: Instead of random damage by free radicals. J Cell Biochem 102:1389-1399
165. Rodwell GEJ, Sonu R, Zahn JM et al (2004) A transcriptional profile of aging in the human kidney. PLoS Biol 2(12):e427