{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:38:55Z","timestamp":1791833935204,"version":"4.3.4"},"reference-count":73,"publisher":"Portland Press Ltd.","issue":"15","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,8,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The klotho gene, named after a Greek goddess who spins the thread of life, was identified as a putative \u2018ageing-suppressor\u2019 gene. Klotho-deficient mice exhibit complex ageing-like phenotypes including hypogonadism, arteriosclerosis (vascular calcification), cardiac hypertrophy, osteopenia, sarcopenia, frailty, and premature death. Klotho protein functions as the obligate co-receptor for fibroblast growth factor-23 (FGF23), a bone-derived hormone that promotes urinary phosphate excretion in response to phosphate intake. Thus, Klotho-deficient mice suffer not only from accelerated ageing but also from phosphate retention due to impaired phosphate excretion. Importantly, restoration of the phosphate balance by placing Klotho-deficient mice on low phosphate diet rescued them from premature ageing, leading us to the notion that phosphate accelerates ageing. Because the extracellular fluid is super-saturated in terms of phosphate and calcium ions, an increase in the phosphate concentration can trigger precipitation of calcium-phosphate. In the blood, calcium-phosphate precipitated upon increase in the blood phosphate concentration is adsorbed by serum protein fetuin-A to form colloidal nanoparticles called calciprotein particles (CPPs). In the urine, CPPs appear in the renal tubular fluid when FGF23 increases phosphate load excreted per nephron. CPPs can induce cell damage, ectopic calcification, and inflammatory responses. CPPs in the blood can induce arteriosclerosis and non-infectious chronic inflammation, whereas CPPs in the urine can induce renal tubular damage and interstitial inflammation\/fibrosis. Thus, we propose that CPPs behave like a pathogen that accelerates ageing and should be regarded as a novel therapeutic target against age-related disorders including chronic kidney disease.<\/jats:p>","DOI":"10.1042\/cs20201453","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T09:37:04Z","timestamp":1628588224000},"page":"1915-1927","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Klotho and calciprotein particles as therapeutic targets against accelerated ageing"],"prefix":"10.1042","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0018-7269","authenticated-orcid":false,"given":"Makoto","family":"Kuro-o","sequence":"first","affiliation":[{"name":"Division of Anti-aging Medicine, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"2021113011230558900_B1","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1126\/science.1197258","article-title":"A bacterium that can grow by using arsenic instead of phosphorus","volume":"332","author":"Wolfe-Simon","year":"2011","journal-title":"Science"},{"key":"2021113011230558900_B2","doi-asserted-by":"publisher","first-page":"R656","DOI":"10.1152\/ajpregu.1992.263.3.R656","article-title":"Behavioral and tissue responses to severe phosphorus depletion in cattle","volume":"263","author":"Blair-West","year":"1992","journal-title":"Am. 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