klotho

Summary

Gene Symbol: klotho
Description: klotho
Alias: alpha-kl, klotho, secreted form of Klotho protein
Species: mouse
Products:     klotho

Top Publications

  1. Olauson H, Lindberg K, Amin R, Jia T, Wernerson A, Andersson G, et al. Targeted deletion of Klotho in kidney distal tubule disrupts mineral metabolism. J Am Soc Nephrol. 2012;23:1641-51 pubmed
    Renal Klotho controls mineral metabolism by directly modulating tubular reabsorption of phosphate and calcium and by acting as a co-receptor for the phosphaturic and vitamin D-regulating hormone fibroblast growth factor-23 (FGF23)...
  2. Thurston R, Larmonier C, Majewski P, Ramalingam R, Midura Kiela M, Laubitz D, et al. Tumor necrosis factor and interferon-gamma down-regulate Klotho in mice with colitis. Gastroenterology. 2010;138:1384-94, 1394.e1-2 pubmed publisher
    b>Klotho (KL) is an anti-inflammatory protein that protects the endothelium from nitric oxide (NO)-induced dysfunction, reduces the expression of endothelial adhesion molecules, and potentially regulates T-cell functions...
  3. Tsujikawa H, Kurotaki Y, Fujimori T, Fukuda K, Nabeshima Y. Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Mol Endocrinol. 2003;17:2393-403 pubmed
    The klotho gene encodes a novel type I membrane protein of beta-glycosidase family and is expressed principally in distal tubule cells of the kidney and choroid plexus in the brain...
  4. Cha S, Ortega B, Kurosu H, Rosenblatt K, Kuro O M, Huang C. Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1. Proc Natl Acad Sci U S A. 2008;105:9805-10 pubmed publisher
    b>Klotho is a mammalian senescence-suppression protein that has homology with glycosidases. The extracellular domain of Klotho is secreted into urine and blood and may function as a humoral factor...
  5. Narumiya H, Sasaki S, Kuwahara N, Irie H, Kusaba T, Kameyama H, et al. HMG-CoA reductase inhibitors up-regulate anti-aging klotho mRNA via RhoA inactivation in IMCD3 cells. Cardiovasc Res. 2004;64:331-6 pubmed
    b>Klotho is thought to play a critical role in the development of age-related disorders including arteriosclerosis. Statins may exert vascular protective effects, independent of the lowering of plasma cholesterol levels...
  6. Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. 2006;444:770-4 pubmed
    ..Here we show that a previously undescribed receptor conversion by Klotho, a senescence-related molecule, generates the FGF23 receptor...
  7. Shiraki Iida T, Aizawa H, Matsumura Y, Sekine S, Iida A, Anazawa H, et al. Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein. FEBS Lett. 1998;424:6-10 pubmed
    ..A defect in expression of a novel gene, termed klotho (kl), leads to a syndrome resembling human aging in mice...
  8. Anour R, Andrukhova O, Ritter E, Zeitz U, Erben R. Klotho lacks a vitamin D independent physiological role in glucose homeostasis, bone turnover, and steady-state PTH secretion in vivo. PLoS ONE. 2012;7:e31376 pubmed publisher
    Apart from its function as co-receptor for fibroblast growth factor-23 (FGF23), Klotho is thought to regulate insulin signaling, intracellular oxidative stress, and parathyroid hormone (PTH) secretion in an FGF23 independent fashion...
  9. Hu M, Shi M, Zhang J, QUINONES H, Griffith C, Kuro O M, et al. Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol. 2011;22:124-36 pubmed publisher
    Soft-tissue calcification is a prominent feature in both chronic kidney disease (CKD) and experimental Klotho deficiency, but whether Klotho deficiency is responsible for the calcification in CKD is unknown...

More Information

Publications65

  1. Ohnishi M, Razzaque M. Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging. FASEB J. 2010;24:3562-71 pubmed publisher
    ..b>Klotho-knockout mice (klotho(-/-)) have a short life span and show numerous physical, biochemical, and morphological ..
  2. Tomiyama K, Maeda R, Urakawa I, Yamazaki Y, Tanaka T, Ito S, et al. Relevant use of Klotho in FGF19 subfamily signaling system in vivo. Proc Natl Acad Sci U S A. 2010;107:1666-71 pubmed publisher
    Alpha-Klotho (alpha-Kl) and its homolog, beta-Klotho (beta-Kl) are key regulators of mineral homeostasis and bile acid/cholesterol metabolism, respectively...
  3. Alexander R, Woudenberg Vrenken T, Buurman J, Dijkman H, van der Eerden B, van Leeuwen J, et al. Klotho prevents renal calcium loss. J Am Soc Nephrol. 2009;20:2371-9 pubmed publisher
    Disturbed calcium (Ca(2+)) homeostasis, which is implicit to the aging phenotype of klotho-deficient mice, has been attributed to altered vitamin D metabolism, but alternative possibilities exist...
  4. Memon F, El Abbadi M, Nakatani T, Taguchi T, Lanske B, Razzaque M. Does Fgf23-klotho activity influence vascular and soft tissue calcification through regulating mineral ion metabolism?. Kidney Int. 2008;74:566-70 pubmed publisher
    Recent studies describe a novel role of fibroblast growth factor-23 (Fgf23)-klotho activity in the systemic regulation of calcium and phosphate homeostasis...
  5. Masuda H, Chikuda H, Suga T, Kawaguchi H, Kuro O M. Regulation of multiple ageing-like phenotypes by inducible klotho gene expression in klotho mutant mice. Mech Ageing Dev. 2005;126:1274-83 pubmed
    Mice carrying a loss-of-function mutation in the klotho gene (KL(-/-) mice) develop ageing-like symptoms around 4 weeks after birth and suffer from multiple age-related disorders observed in humans, including osteoporosis, ..
  6. Utsugi T, Ohno T, Ohyama Y, Uchiyama T, Saito Y, Matsumura Y, et al. Decreased insulin production and increased insulin sensitivity in the klotho mutant mouse, a novel animal model for human aging. Metabolism. 2000;49:1118-23 pubmed
    We have recently identified a novel gene, klotho (kl), which may suppress several aging phenotypes...
  7. Imura A, Iwano A, Tohyama O, Tsuji Y, Nozaki K, Hashimoto N, et al. Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane. FEBS Lett. 2004;565:143-7 pubmed
    b>Klotho mutant mice exhibit a set of phenotypes resembling human ageing. Although the function of Klotho remains unclear, mediation of its pleiotropic functions by putative humoral factor(s) has been presumed...
  8. Yamamoto M, Clark J, Pastor J, Gurnani P, Nandi A, Kurosu H, et al. Regulation of oxidative stress by the anti-aging hormone klotho. J Biol Chem. 2005;280:38029-34 pubmed
    b>klotho is an aging suppressor gene and extends life span when overexpressed in mice. Klotho protein was recently demonstrated to function as a hormone that inhibits insulin/insulin-like growth factor-1 (IGF-1) signaling...
  9. Andrukhova O, Zeitz U, Goetz R, Mohammadi M, Lanske B, Erben R. FGF23 acts directly on renal proximal tubules to induce phosphaturia through activation of the ERK1/2-SGK1 signaling pathway. Bone. 2012;51:621-8 pubmed publisher
    ..of circulating FGF23 to FGF receptors in the cell membrane requires the concurrent presence of the co-receptor ?Klotho. It is still controversial whether ?Klotho is expressed in the kidney proximal tubule, the principal site of ..
  10. Forster R, Jurutka P, Hsieh J, Haussler C, Lowmiller C, Kaneko I, et al. Vitamin D receptor controls expression of the anti-aging klotho gene in mouse and human renal cells. Biochem Biophys Res Commun. 2011;414:557-62 pubmed publisher
    Isoforms of the mammalian klotho protein serve as membrane co-receptors that regulate renal phosphate and calcium reabsorption...
  11. Sugiura H, Yoshida T, Mitobe M, Yoshida S, Shiohira S, Nitta K, et al. Klotho reduces apoptosis in experimental ischaemic acute kidney injury via HSP-70. Nephrol Dial Transplant. 2010;25:60-8 pubmed publisher
    High Klotho expression has been detected in the kidney, and since the results of a recent study suggested that Klotho induction mitigates ischaemic damage in the kidney, in the present study we explored the mechanism by which Klotho ..
  12. Kuro O M. Klotho and aging. Biochim Biophys Acta. 2009;1790:1049-58 pubmed publisher
    The klotho gene encodes a single-pass transmembrane protein that forms a complex with multiple fibroblast growth factor (FGF) receptors and functions as an obligatory co-receptor for FGF23, a bone-derived hormone that induces negative ..
  13. Nakatani T, Sarraj B, Ohnishi M, Densmore M, Taguchi T, Goetz R, et al. In vivo genetic evidence for klotho-dependent, fibroblast growth factor 23 (Fgf23) -mediated regulation of systemic phosphate homeostasis. FASEB J. 2009;23:433-41 pubmed publisher
    ..strikingly similar physical, morphological, and biochemical phenotypes of fibroblast growth factor 23 (Fgf23) and klotho ablated mice, which led to identification of klotho as an Fgf23 signaling cofactor...
  14. Mitobe M, Yoshida T, Sugiura H, Shirota S, Tsuchiya K, Nihei H. Oxidative stress decreases klotho expression in a mouse kidney cell line. Nephron Exp Nephrol. 2005;101:e67-74 pubmed
    Defects in klotho gene expression in the mouse result in a syndrome that resembles human aging...
  15. Chang Q, Hoefs S, Van Der Kemp A, Topala C, Bindels R, Hoenderop J. The beta-glucuronidase klotho hydrolyzes and activates the TRPV5 channel. Science. 2005;310:490-3 pubmed
    ..We report here that TRPV5 is stimulated by the mammalian hormone klotho. Klotho, a beta-glucuronidase, hydrolyzes extracellular sugar residues on TRPV5, entrapping the channel in the ..
  16. Kurosu H, Yamamoto M, Clark J, Pastor J, Nandi A, Gurnani P, et al. Suppression of aging in mice by the hormone Klotho. Science. 2005;309:1829-33 pubmed
    A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span...
  17. Brownstein C, Zhang J, Stillman A, Ellis B, Troiano N, Adams D, et al. Increased bone volume and correction of HYP mouse hypophosphatemia in the Klotho/HYP mouse. Endocrinology. 2010;151:492-501 pubmed publisher
    ..FGF23 action is dependent upon Klotho, which converts FGF receptor 1 into an FGF23-specific receptor...
  18. Kuro O M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997;390:45-51 pubmed
    A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes...
  19. Yoon H, Lim S, Piao S, Song J, Kim J, Yang C. Statin upregulates the expression of klotho, an anti-aging gene, in experimental cyclosporine nephropathy. Nephron Exp Nephrol. 2012;120:e123-33 pubmed publisher
    ..reported that long-term cyclosporine (CsA)-induced oxidative stress is associated with decreased expression of klotho, an anti-aging gene...
  20. Doi S, Zou Y, Togao O, Pastor J, John G, Wang L, et al. Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice. J Biol Chem. 2011;286:8655-65 pubmed publisher
    ..ureteral obstruction and metastasis of human cancer xenografts are suppressed by administration of secreted Klotho protein to mice. Klotho is a single-pass transmembrane protein expressed in renal tubular epithelial cells...
  21. Yamashita T, Nabeshima Y, Noda M. High-resolution micro-computed tomography analyses of the abnormal trabecular bone structures in klotho gene mutant mice. J Endocrinol. 2000;164:239-45 pubmed
    Inactivation mutation of the recently discovered klotho gene in mice causes a syndrome resembling aging. Manifestations include short life span, atherosclerosis, gonadal atropy, skin atropy, emphysema, ataxia and ectopic calcification...
  22. Nagai R, Saito Y, Ohyama Y, Aizawa H, Suga T, Nakamura T, et al. 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. 2000;57:738-46 pubmed
    ..We recently identified the klotho gene as a possible regulator of human aging...
  23. Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt K, et al. Regulation of fibroblast growth factor-23 signaling by klotho. J Biol Chem. 2006;281:6120-3 pubmed
    The aging suppressor gene Klotho encodes a single-pass transmembrane protein...
  24. Li S, Watanabe M, Yamada H, Nagai A, Kinuta M, Takei K. Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice. Cell Struct Funct. 2004;29:91-9 pubmed
    b>Klotho mutant mouse (kl-/-), a mouse model for human aging, exhibits various phenotypes in a wide range of organs including arteriosclerosis, neural degeneration, skin and gonadal atrophy, pulmonary emphysema, calcification of soft ..
  25. Segawa H, Yamanaka S, Ohno Y, Onitsuka A, Shiozawa K, Aranami F, et al. Correlation between hyperphosphatemia and type II Na-Pi cotransporter activity in klotho mice. Am J Physiol Renal Physiol. 2007;292:F769-79 pubmed
    Recent studies have demonstrated that klotho protein plays a role in calcium/phosphate homeostasis. The goal of the present study was to investigate the regulation of Na-P(i) cotransporters in klotho mutant (kl/kl) mice...
  26. Ohnishi M, Nakatani T, Lanske B, Razzaque M. Reversal of mineral ion homeostasis and soft-tissue calcification of klotho knockout mice by deletion of vitamin D 1alpha-hydroxylase. Kidney Int. 2009;75:1166-1172 pubmed publisher
    Changes in the expression of klotho, a beta-glucuronidase, contribute to the development of features that resemble those of premature aging, as well as chronic renal failure...
  27. Tohyama O, Imura A, Iwano A, Freund J, Henrissat B, Fujimori T, et al. Klotho is a novel beta-glucuronidase capable of hydrolyzing steroid beta-glucuronides. J Biol Chem. 2004;279:9777-84 pubmed
    b>klotho mutant mice provide a unique model to analyze mechanisms of aging because their phenotypes resemble those of human aging-associated disorders...
  28. Hu M, Shi M, Zhang J, Pastor J, Nakatani T, Lanske B, et al. Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB J. 2010;24:3438-50 pubmed publisher
    b>Klotho has profound effects on phosphate metabolism, but the mechanisms of how Klotho affects phosphate homeostasis is unknown...
  29. Liu H, Fergusson M, Castilho R, Liu J, Cao L, Chen J, et al. Augmented Wnt signaling in a mammalian model of accelerated aging. Science. 2007;317:803-6 pubmed
    ..We explored this concept in the Klotho mouse model of accelerated aging...
  30. Moreno J, Izquierdo M, Sanchez Niño M, Suarez Alvarez B, Lopez Larrea C, Jakubowski A, et al. The inflammatory cytokines TWEAK and TNF? reduce renal klotho expression through NF?B. J Am Soc Nephrol. 2011;22:1315-25 pubmed publisher
    ..One candidate effector is Klotho, a protein expressed by renal cells that has antiaging properties; Klotho-deficient mice have an accelerated aging-..
  31. Yuan Q, Sato T, Densmore M, Saito H, Schüler C, Erben R, et al. FGF-23/Klotho signaling is not essential for the phosphaturic and anabolic functions of PTH. J Bone Miner Res. 2011;26:2026-35 pubmed publisher
    ..This study evaluated the effect of FGF-23/Klotho signaling on the phosphaturic and anabolic functions of PTH...
  32. Zhang H, Li Y, Fan Y, Wu J, Zhao B, Guan Y, et al. Klotho is a target gene of PPAR-gamma. Kidney Int. 2008;74:732-9 pubmed publisher
    b>Klotho is an anti-aging gene whose expression is regulated by many stimuli. Here we examined the transcriptional regulation of the klotho gene by peroxisome proliferator-activated receptor-gamma (PPAR-gamma)...
  33. Haruna Y, Kashihara N, Satoh M, Tomita N, Namikoshi T, Sasaki T, et al. Amelioration of progressive renal injury by genetic manipulation of Klotho gene. Proc Natl Acad Sci U S A. 2007;104:2331-6 pubmed
    b>Klotho, an antiaging gene with restricted organ distribution, is mainly expressed in the kidney tubules; the mutant mice have shortened life span, arteriosclerosis, anemia, and osteoporesis, features common to patients with chronic renal ..
  34. Imura A, Tsuji Y, Murata M, Maeda R, Kubota K, Iwano A, et al. alpha-Klotho as a regulator of calcium homeostasis. Science. 2007;316:1615-8 pubmed
    alpha-klotho was identified as a gene associated with premature aging-like phenotypes characterized by short lifespan...
  35. Fischer S, Kempe D, Leibrock C, Rexhepaj R, Siraskar B, Boini K, et al. Hyperaldosteronism in Klotho-deficient mice. Am J Physiol Renal Physiol. 2010;299:F1171-7 pubmed publisher
    b>Klotho is a membrane protein participating in the inhibitory effect of FGF23 on the formation of 1,25-dihydroxyvitamin-D(3) [1,25(OH)(2)D(3)]...
  36. Medici D, Razzaque M, DeLuca S, Rector T, Hou B, Kang K, et al. FGF-23-Klotho signaling stimulates proliferation and prevents vitamin D-induced apoptosis. J Cell Biol. 2008;182:459-65 pubmed publisher
    Fibroblast growth factor 23 (FGF-23) and Klotho are secretory proteins that regulate mineral-ion metabolism...
  37. Yoshida T, Fujimori T, Nabeshima Y. Mediation of unusually high concentrations of 1,25-dihydroxyvitamin D in homozygous klotho mutant mice by increased expression of renal 1alpha-hydroxylase gene. Endocrinology. 2002;143:683-9 pubmed
    Homozygous klotho mutant (kl-/-) mice exhibit multiple phenotypes resembling human aging...
  38. Nakatani T, Ohnishi M, Razzaque M. Inactivation of klotho function induces hyperphosphatemia even in presence of high serum fibroblast growth factor 23 levels in a genetically engineered hypophosphatemic (Hyp) mouse model. FASEB J. 2009;23:3702-11 pubmed publisher
    ..concomitant hypophosphatemia in Hyp mice and to evaluate whether FGF23 activity could be modified by manipulating klotho (a cofactor of FGF23 signaling). We generated Hyp and klotho double-mutant mice (Hyp/klotho(-/-))...
  39. Andrukhova O, Smorodchenko A, Egerbacher M, Streicher C, Zeitz U, Goetz R, et al. FGF23 promotes renal calcium reabsorption through the TRPV5 channel. EMBO J. 2014;33:229-46 pubmed publisher
    b>Klotho is thought to activate the epithelial calcium channel Transient Receptor Potential Vanilloid-5 (TRPV5) in distal renal tubules through its putative glucuronidase/sialidase activity, thereby preventing renal calcium loss...
  40. Kato Y, Arakawa E, Kinoshita S, Shirai A, Furuya A, Yamano K, et al. Establishment of the anti-Klotho monoclonal antibodies and detection of Klotho protein in kidneys. Biochem Biophys Res Commun. 2000;267:597-602 pubmed
    A novel gene, klotho (kl), which is involved in the development of a syndrome resembling human aging in mice, was recently identified...
  41. Hu M, Shi M, Zhang J, QUINONES H, Kuro O M, Moe O. Klotho deficiency is an early biomarker of renal ischemia-reperfusion injury and its replacement is protective. Kidney Int. 2010;78:1240-51 pubmed publisher
    b>Klotho is an antiaging substance with pleiotropic actions including regulation of mineral metabolism. It is highly expressed in the kidney and is present in the circulation and urine but its role in acute kidney injury (AKI) is unknown...
  42. Smith R, O Bryan L, Farrow E, Summers L, Clinkenbeard E, Roberts J, et al. Circulating ?Klotho influences phosphate handling by controlling FGF23 production. J Clin Invest. 2012;122:4710-5 pubmed publisher
    The FGF23 coreceptor ?Klotho (?KL) is expressed as a membrane-bound protein (mKL) that forms heteromeric complexes with FGF receptors (FGFRs) to initiate intracellular signaling...
  43. Xie J, Cha S, An S, Kuro O M, Birnbaumer L, Huang C. Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart. Nat Commun. 2012;3:1238 pubmed publisher
    b>Klotho is a membrane protein predominantly produced in the kidney that exerts some antiageing effects. Ageing is associated with an increased risk of heart failure; whether Klotho is cardioprotective is unknown...
  44. Faul C, Amaral A, Oskouei B, Hu M, Sloan A, Isakova T, et al. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011;121:4393-408 pubmed publisher
    ..FGF receptor-dependent activation of the calcineurin-NFAT signaling pathway, but this effect was independent of klotho, the coreceptor for FGF23 in the kidney and parathyroid glands...
  45. Sugiura H, Yoshida T, Tsuchiya K, Mitobe M, Nishimura S, Shirota S, et al. Klotho reduces apoptosis in experimental ischaemic acute renal failure. Nephrol Dial Transplant. 2005;20:2636-45 pubmed
    b>Klotho is associated with the suppression of several ageing phenotypes...
  46. King G, Chen C, Huang M, Zeldich E, Brazee P, Schuman E, et al. Identification of novel small molecules that elevate Klotho expression. Biochem J. 2012;441:453-61 pubmed publisher
    The absence of Klotho (KL) from mice causes the development of disorders associated with human aging and decreased longevity, whereas increased expression prolongs lifespan...
  47. Zhao Y, Banerjee S, Dey N, LeJeune W, Sarkar P, Brobey R, et al. Klotho depletion contributes to increased inflammation in kidney of the db/db mouse model of diabetes via RelA (serine)536 phosphorylation. Diabetes. 2011;60:1907-16 pubmed publisher
    b>Klotho is an antiaging hormone present in the kidney that extends the lifespan, regulates kidney function, and modulates cellular responses to oxidative stress...
  48. Goetz R, Nakada Y, Hu M, Kurosu H, Wang L, Nakatani T, et al. Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation. Proc Natl Acad Sci U S A. 2010;107:407-12 pubmed publisher
    Fibroblast growth factor (FGF) 23 inhibits renal phosphate reabsorption by activating FGF receptor (FGFR) 1c in a Klotho-dependent fashion...
  49. Yu J, Deng M, Zhao J, Huang L. Decreased expression of klotho gene in uremic atherosclerosis in apolipoprotein E-deficient mice. Biochem Biophys Res Commun. 2010;391:261-6 pubmed publisher
    ..The klotho gene, predominantly expressed in the kidney, plays a key role in regulating aging and the development of age-..
  50. Bloch L, Sineshchekova O, Reichenbach D, Reiss K, Saftig P, Kuro O M, et al. Klotho is a substrate for alpha-, beta- and gamma-secretase. FEBS Lett. 2009;583:3221-4 pubmed publisher
    b>Klotho is an anti-aging protein with different functions of the full-length membrane protein and the secreted hormone-like form...
  51. Sugiura H, Yoshida T, Shiohira S, Kohei J, Mitobe M, Kurosu H, et al. Reduced Klotho expression level in kidney aggravates renal interstitial fibrosis. Am J Physiol Renal Physiol. 2012;302:F1252-64 pubmed publisher
    Renal expression of the klotho gene is markedly suppressed in chronic kidney disease (CKD)...
  52. Zhou H, Zeng C, Yang T, Long F, Kuang X, Du J. Lentivirus-mediated klotho up-regulation improves aging-related memory deficits and oxidative stress in senescence-accelerated mouse prone-8 mice. Life Sci. 2018;200:56-62 pubmed publisher
    Oxidative stress caused by aging aggravates neuropathological changes and cognitive deficits. Klotho, an anti-aging protein, shows an anti-oxidative effect...
  53. Agarwal I, Ide N, Ix J, Kestenbaum B, Lanske B, Schiller N, et al. Fibroblast growth factor-23 and cardiac structure and function. J Am Heart Assoc. 2014;3:e000584 pubmed publisher
    ..Whether FGF-23 acts directly to induce left ventricular hypertrophy, potentially independent of its klotho coreceptor, remains uncertain...
  54. Patel M, Donaldson A, Lewis A, Natanek S, Lee J, Andersson Y, et al. Klotho and smoking--An interplay influencing the skeletal muscle function deficits that occur in COPD. Respir Med. 2016;113:50-6 pubmed publisher
    b>Klotho is an 'anti-ageing' hormone and transmembrane protein; Klotho deficient mice develop a similar ageing phenotype to smokers including emphysema and muscle wasting...
  55. van Ark J, Hammes H, van Dijk M, Lexis C, van der Horst I, Zeebregts C, et al. Circulating alpha-klotho levels are not disturbed in patients with type 2 diabetes with and without macrovascular disease in the absence of nephropathy. Cardiovasc Diabetol. 2013;12:116 pubmed publisher
    ..Circulating soluble-Klotho (sKlotho) is produced in the kidney and is a putative anti-aging and vasculoprotective hormone...
  56. Hasegawa T, Yamamoto T, Hongo H, Tsuboi K, Amizuka N. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Vascular calcification in klotho deficient environment]. Clin Calcium. 2015;25:693-9 pubmed publisher
    b>Klotho deficient (kl/kl) mice exhibit Möncheberg's vascular calcification in the tunica media due to hyperphosphatemia and hypercalcemia by mediating the disrupted signaling of FGF23/klotho axis...