{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T06:37:10Z","timestamp":1777617430340,"version":"3.51.4"},"reference-count":51,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T00:00:00Z","timestamp":1588204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["N01-AG-6-2101"],"award-info":[{"award-number":["N01-AG-6-2101"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["N01-AG-6-2103"],"award-info":[{"award-number":["N01-AG-6-2103"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["N01-AG-6-2106"],"award-info":[{"award-number":["N01-AG-6-2106"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01-AG028050"],"award-info":[{"award-number":["R01-AG028050"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG027002"],"award-info":[{"award-number":["R01AG027002"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG027012"],"award-info":[{"award-number":["R01 AG027012"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K23DK105327"],"award-info":[{"award-number":["K23DK105327"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG048069"],"award-info":[{"award-number":["R01AG048069"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000056","name":"National Institute of Nursing Research","doi-asserted-by":"publisher","award":["R01-NR012459"],"award-info":[{"award-number":["R01-NR012459"]}],"id":[{"id":"10.13039\/100000056","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>\u03b1Klotho is a hormone and co-receptor for fibroblast growth factor 23 (FGF23), a hormone that downregulates active vitamin D synthesis and promotes phosphate excretion. Low \u03b1Klotho and high FGF23 occur in chronic kidney disease (CKD).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We aimed to assess the relationships of \u03b1Klotho and FGF23 with mobility disability in community-dwelling older adults.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and Setting<\/jats:title>\n                  <jats:p>We estimated associations of plasma-soluble \u03b1Klotho and serum FGF23 concentrations with mobility disability over 6 years. Additional analyses was stratified by CKD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Participants included 2751 adults (25.0% with CKD), aged 71 to 80 years, from the 1998 to 1999 Health, Aging, and Body Composition Study visit.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>Walking disability and stair climb disability were defined as self-reported \u201ca lot of difficulty\u201d or an inability to walk a quarter mile and climb 10 stairs, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Median (interquartile range [IQR]) serum FGF23 and plasma soluble \u03b1Klotho concentrations were 46.6 (36.7, 60.2) pg\/mL and 630.4 (478.4, 816.0) pg\/mL, respectively. After adjustment, higher \u03b1Klotho concentrations were associated with lower walking disability rates (Rate Ratio [RR] highest vs. lowest tertile\u2005=\u20050.74; 95% confidence interval l [CI]\u2005=\u20050.62, 0.89; P\u2005=\u20050.003). Higher FGF23 concentrations were associated with higher walking disability rates (RR highest vs. lowest tertile\u2005=\u20051.24; 95%CI\u2005=\u20051.03, 1.50; P\u2005=\u20050.005). Overall, higher \u03b1Klotho combined with lower FGF23 was associated with the lowest walking disability rates (P for interaction\u2005=\u20050.023). Stair climb disability findings were inconsistent. No interactions with CKD were statistically significant (P for interaction\u2005&amp;gt;\u20050.10).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Higher plasma soluble \u03b1Klotho and lower serum FGF23 concentrations were associated with lower walking disability rates in community-dwelling older adults, particularly those without CKD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jendso\/bvz032","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T18:47:37Z","timestamp":1588272457000},"source":"Crossref","is-referenced-by-count":7,"title":["Plasma Soluble \u03b1Klotho, Serum Fibroblast Growth Factor 23, and Mobility Disability in Community-Dwelling Older Adults"],"prefix":"10.1210","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5283-2082","authenticated-orcid":false,"given":"Michelle","family":"Shardell","sequence":"first","affiliation":[{"name":"Institute for Genome Sciences, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A","family":"Drew","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard D","family":"Semba","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Johns Hopkins Medical Institutions, Baltimore, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara B","family":"Harris","sequence":"first","affiliation":[{"name":"Laboratory of Epidemiology and Population Science, National Institute on Aging Intramural Research Program, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peggy M","family":"Cawthon","sequence":"first","affiliation":[{"name":"Research Institute, California Pacific Medical Center, San Francisco, California"},{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleanor M","family":"Simonsick","sequence":"first","affiliation":[{"name":"Translational Gerontology Branch, National Institute on Aging Intramural Research Program, Baltimore, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita R","family":"Kalyani","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Metabolism, and Diabetes, Johns Hopkins Medical Institutions, Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann V","family":"Schwartz","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen B","family":"Kritchevsky","sequence":"first","affiliation":[{"name":"Sticht Center for Healthy Aging and Alzheimer\u2019s Prevention, Wake Forest University, Winston-Salem, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne B","family":"Newman","sequence":"first","affiliation":[{"name":"Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2020,4,30]]},"reference":[{"issue":"1","key":"2020050814174844700_CIT0001","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41581-018-0078-3","article-title":"The Klotho proteins in health and disease","volume":"15","author":"Kuro-o","year":"2019","journal-title":"Nat Rev Nephrol."},{"issue":"6655","key":"2020050814174844700_CIT0002","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/36285","article-title":"Mutation of the mouse klotho gene leads to a syndrome resembling ageing","volume":"390","author":"Kuro-o","year":"1997","journal-title":"Nature."},{"issue":"5742","key":"2020050814174844700_CIT0003","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1126\/science.1112766","article-title":"Suppression of aging in mice by the hormone Klotho","volume":"309","author":"Kurosu","year":"2005","journal-title":"Science."},{"issue":"4","key":"2020050814174844700_CIT0004","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1002\/jnr.1087","article-title":"Neurofilaments of Klotho, the mutant mouse prematurely displaying symptoms resembling human aging","volume":"64","author":"Uchida","year":"2001","journal-title":"J Neurosci Res."},{"issue":"9","key":"2020050814174844700_CIT0005","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1093\/gerona\/glv017","article-title":"Serum 25-hydroxyvitamin D, plasma Klotho, and lower-extremity physical performance among older adults: findings from the InCHIANTI study","volume":"70","author":"Shardell","year":"2015","journal-title":"J Gerontol A Biol Sci Med Sci."},{"issue":"1","key":"2020050814174844700_CIT0006","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/gerona\/glv077","article-title":"Low plasma Klotho concentrations and decline of knee strength in older adults","volume":"71","author":"Semba","year":"2016","journal-title":"J Gerontol A Biol Sci Med Sci."},{"issue":"4","key":"2020050814174844700_CIT0007","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1007\/s00421-011-2072-3","article-title":"Relationship of low plasma klotho with poor grip strength in older community-dwelling adults: the InCHIANTI study","volume":"112","author":"Semba","year":"2012","journal-title":"Eur J Appl Physiol."},{"issue":"7","key":"2020050814174844700_CIT0008","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1093\/gerona\/glx202","article-title":"Plasma Klotho and frailty in older adults: findings from the InCHIANTI study","volume":"74","author":"Shardell","year":"2019","journal-title":"J Gerontol A Biol Sci Med Sci."},{"issue":"5","key":"2020050814174844700_CIT0009","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1093\/gerona\/glv140","article-title":"Plasma Klotho and cognitive decline in older adults: findings from the InCHIANTI study","volume":"71","author":"Shardell","year":"2016","journal-title":"J Gerontol A Biol Sci Med Sci."},{"issue":"6","key":"2020050814174844700_CIT0010","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1681\/ASN.2016080828","article-title":"Association between soluble Klotho and change in kidney function: the health aging and body composition study","volume":"28","author":"Drew","year":"2017","journal-title":"J Am Soc Nephrol."},{"issue":"7","key":"2020050814174844700_CIT0011","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1093\/gerona\/glr058","article-title":"Plasma klotho and mortality risk in older community-dwelling adults","volume":"66","author":"Semba","year":"2011","journal-title":"J Gerontol A Biol Sci Med Sci."},{"issue":"3","key":"2020050814174844700_CIT0012","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1359\/JBMR.0301264","article-title":"FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis","volume":"19","author":"Shimada","year":"2004","journal-title":"J Bone Miner Res."},{"issue":"7120","key":"2020050814174844700_CIT0013","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/nature05315","article-title":"Klotho converts canonical FGF receptor into a specific receptor for FGF23","volume":"444","author":"Urakawa","year":"2006","journal-title":"Nature."},{"issue":"5","key":"2020050814174844700_CIT0014","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1681\/ASN.2005111185","article-title":"Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D","volume":"17","author":"Liu","year":"2006","journal-title":"J Am Soc Nephrol."},{"issue":"1","key":"2020050814174844700_CIT0015","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/ki.2013.271","article-title":"Early chronic kidney disease-mineral bone disorder stimulates vascular calcification","volume":"85","author":"Fang","year":"2014","journal-title":"Kidney Int."},{"issue":"10","key":"2020050814174844700_CIT0016","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1681\/ASN.2010121224","article-title":"FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis","volume":"22","author":"Kendrick","year":"2011","journal-title":"J Am Soc Nephrol."},{"issue":"5","key":"2020050814174844700_CIT0017","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/nrneph.2014.49","article-title":"Roles of phosphate and fibroblast growth factor 23 in cardiovascular disease","volume":"10","author":"Scialla","year":"2014","journal-title":"Nat Rev Nephrol."},{"issue":"4","key":"2020050814174844700_CIT0018","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1681\/ASN.2016040401","article-title":"Fibroblast growth factor 23 and the risk of infection-related hospitalization in older adults","volume":"28","author":"Nowak","year":"2017","journal-title":"J Am Soc Nephrol."},{"issue":"2","key":"2020050814174844700_CIT0019","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1681\/ASN.2017070772","article-title":"Longitudinal FGF23 trajectories and mortality in patients with CKD","volume":"29","author":"Isakova","year":"2018","journal-title":"J Am Soc Nephrol."},{"issue":"23","key":"2020050814174844700_CIT0020","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1001\/jama.2011.826","article-title":"Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease","volume":"305","author":"Isakova","year":"2011","journal-title":"JAMA."},{"issue":"6","key":"2020050814174844700_CIT0021","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1056\/NEJMoa0706130","article-title":"Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis","volume":"359","author":"Guti\u00e9rrez","year":"2008","journal-title":"N Engl J Med."},{"issue":"7689","key":"2020050814174844700_CIT0022","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nature25451","article-title":"\u03b1-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling","volume":"553","author":"Chen","year":"2018","journal-title":"Nature."},{"issue":"3","key":"2020050814174844700_CIT0023","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1089\/rej.2011.1268","article-title":"Relationship of low-circulating \u201canti-aging\u201d klotho hormone with disability in activities of daily living among older community-dwelling adults","volume":"15","author":"Crasto","year":"2012","journal-title":"Rejuvenation Res."},{"issue":"7","key":"2020050814174844700_CIT0024","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1177\/0164027514550834","article-title":"Development of an expanded measure of physical functioning for older persons in epidemiologic research","volume":"37","author":"Gross","year":"2015","journal-title":"Res Aging."},{"issue":"5","key":"2020050814174844700_CIT0025","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1093\/ptj\/86.5.726","article-title":"Toward a common language for function, disability, and health","volume":"86","author":"Jette","year":"2006","journal-title":"Phys Ther."},{"issue":"3","key":"2020050814174844700_CIT0026","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1093\/gerona\/60.3.324","article-title":"Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons","volume":"60","author":"Visser","year":"2005","journal-title":"J Gerontol A Biol Sci Med Sci."},{"issue":"3","key":"2020050814174844700_CIT0027","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/1047-2797(91)90005-W","article-title":"The Cardiovascular Health Study: design and rationale","volume":"1","author":"Fried","year":"1991","journal-title":"Ann Epidemiol."},{"issue":"5","key":"2020050814174844700_CIT0028","doi-asserted-by":"crossref","first-page":"M206","DOI":"10.1093\/gerona\/51A.5.M206","article-title":"Functional decline in older adults: expanding methods of 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Cardiovascular Health Study Research Group","volume":"47","author":"Fried","year":"1994","journal-title":"J Clin Epidemiol."},{"issue":"3","key":"2020050814174844700_CIT0030","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.bbrc.2010.06.110","article-title":"Establishment of sandwich ELISA for soluble alpha-Klotho measurement: age-dependent change of soluble alpha-Klotho levels in healthy subjects","volume":"398","author":"Yamazaki","year":"2010","journal-title":"Biochem Biophys Res Commun."},{"key":"2020050814174844700_CIT0031","author":"RRID:AB_2750859"},{"issue":"4","key":"2020050814174844700_CIT0032","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/jbmr.2750","article-title":"Associations of FGF23 with change in bone mineral density and fracture risk in older individuals","volume":"31","author":"Isakova","year":"2016","journal-title":"J Bone Miner 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death","volume":"16","author":"Shardell","year":"2015","journal-title":"Biostatistics."},{"issue":"2","key":"2020050814174844700_CIT0040","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/ndt\/gfu291","article-title":"The demonstration of \u03b1Klotho deficiency in human chronic kidney disease with a novel synthetic antibody","volume":"30","author":"Barker","year":"2015","journal-title":"Nephrol Dial Transplant."},{"issue":"1","key":"2020050814174844700_CIT0041","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1681\/ASN.2009121311","article-title":"Klotho deficiency causes vascular calcification in chronic kidney disease","volume":"22","author":"Hu","year":"2011","journal-title":"J Am Soc Nephrol."},{"issue":"5","key":"2020050814174844700_CIT0042","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1530\/EJE-11-0577","article-title":"Relationship of serum fibroblast growth factor 23 with cardiovascular disease in older community-dwelling women","volume":"165","author":"Dalal","year":"2011","journal-title":"Eur J Endocrinol."},{"issue":"1","key":"2020050814174844700_CIT0043","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2215\/CJN.08070811","article-title":"Serum fibroblast growth factor-23 and risk of incident chronic kidney disease in older community-dwelling women","volume":"7","author":"Semba","year":"2012","journal-title":"Clin J Am Soc Nephrol."},{"issue":"12","key":"2020050814174844700_CIT0044","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1038\/ki.2010.328","article-title":"Klotho deficiency is an early biomarker of renal ischemia-reperfusion injury and its replacement is protective","volume":"78","author":"Hu","year":"2010","journal-title":"Kidney Int."},{"issue":"1","key":"2020050814174844700_CIT0045","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1124\/mol.109.055780","article-title":"Regulation of renal outer medullary potassium channel and renal K(+) excretion by 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