{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:42:53Z","timestamp":1787877773043,"version":"build-2784847793"},"reference-count":200,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000901","name":"Juvenile Diabetes Research Foundation International","doi-asserted-by":"publisher","award":["2-SRA-2018-497-A-B"],"award-info":[{"award-number":["2-SRA-2018-497-A-B"]}],"id":[{"id":"10.13039\/100000901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007476","name":"Diabetes Canada","doi-asserted-by":"publisher","award":["OG-3-13-4066"],"award-info":[{"award-number":["OG-3-13-4066"]}],"id":[{"id":"10.13039\/100007476","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"publisher","award":["81570518, 81630020, 82370814"],"award-info":[{"award-number":["81570518, 81630020, 82370814"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"St. Michael's Hospital Foundation, Toronto, Canada","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Keenan Research Centre for Biomedical Science, Toronto, Canada","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mice genetically deficient in \u03b1-Klotho (henceforth Klotho) display accelerated aging. The mechanisms are only partially understood. Here, we examine how these relate to the 12 hallmarks of aging consisting of chronic inflammation (inflammaging), as well as damaging changes to the genome (DNA damage), telomeres, epigenetic regulation, proteostasis, nutrient sensing, mitochondria, stem cells, intercellular communication, macroautophagy, microbiome and cell replication (senescence). Inflammation aggravates the other hallmarks. We report that Klotho counters the majority of these hallmarks. It ameliorates mitochondrial function and reduces reactive oxygen species (ROS), telomere attrition and cellular senescence. It protects against inflammation by inhibiting NF-\u03baB and the NLRP3 inflammasome. This applies to inflammaging, several chronic inflammatory diseases, atherosclerosis, diabetes, and Alzheimer\u2019s disease. Klotho also counters some aging factors outside of these hallmarks. Low Klotho (often due to kidney disease) produces hyperphosphatemia, which injures cells (especially endothelial cells) and promotes aging. Another key action of Klotho is the mitigation of fibrosis in major organs (kidneys, heart, lungs and other), mainly through the inhibition of TGF-\u03b2 and Wnt. Klotho also protects against muscle atrophy (sarcopenia)\u2014a common feature of aging\u2014and exhibits anti-cancer activity. We describe several factors that increase Klotho, and are potentially amenable to clinical therapy.<\/jats:p>","DOI":"10.3390\/cells15060507","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T14:46:31Z","timestamp":1773326791000},"page":"507","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antiaging Properties of the Klotho Protein"],"prefix":"10.3390","volume":"15","author":[{"given":"G\u00e9rald J.","family":"Prud\u2019homme","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Unity Health Toronto, Toronto, ON M5B 1W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai 200433, China"},{"name":"Shanghai Innogen Pharmaceutical Co., Ltd., Shanghai 200135, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Novillo-Sarmiento, C., Garc\u00eda-S\u00e1ez, R.M., Rivas-Dom\u00ednguez, A., Torralba-Duque, A., Rodelo-Haad, C., Rodr\u00edguez-Ortiz, M.E., Mu\u00f1oz-Casta\u00f1eda, J.R., and Pend\u00f3n-RuizdeMier, M.V. 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