{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:50:52Z","timestamp":1791669052389,"version":"4.3.4"},"reference-count":240,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Ageing Research Reviews"],"published-print":{"date-parts":[[2027,1]]},"DOI":"10.1016\/j.arr.2026.103390","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:52:31Z","timestamp":1791442351000},"page":"103390","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Klotho within cardio-renal-hepatic-metabolic health: Integrating mineral metabolism, organ crosstalk, and therapeutic opportunities"],"prefix":"10.1016","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7931-2413","authenticated-orcid":false,"given":"Sanika","family":"Taigade","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddhi Bagwe","family":"Parab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8490-0705","authenticated-orcid":false,"given":"Gaurav","family":"Doshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.arr.2026.103390_bib1","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1150222","article-title":"Biological and pharmacological functions of the FGF19- and FGF21-coreceptor beta klotho","volume":"14","author":"Aaldijk","year":"2023","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.arr.2026.103390_bib2","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.matbio.2020.04.005","article-title":"Targeting the renin-angiotensin-aldosterone system in fibrosis","volume":"91\u201392","author":"AlQudah","year":"2020","journal-title":"Matrix Biol."},{"key":"10.1016\/j.arr.2026.103390_bib3","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1080\/02640414.2019.1626048","article-title":"Exercise training increases the S-Klotho plasma levels in sedentary middle-aged adults: A randomised controlled trial. The FIT-AGEING study","volume":"37","author":"Amaro-Gahete","year":"2019","journal-title":"J. Sports Sci."},{"key":"10.1016\/j.arr.2026.103390_bib4","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s41574-021-00626-7","article-title":"Mitochondrial and metabolic dysfunction in ageing and age-related diseases","volume":"18","author":"Amorim","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.arr.2026.103390_bib5","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1002\/hep.29375","article-title":"USP18 protects against hepatic steatosis and insulin resistance through its deubiquitinating activity","volume":"66","author":"An","year":"2017","journal-title":"Hepatology"},{"key":"10.1016\/j.arr.2026.103390_bib6","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1038\/ki.2012.440","article-title":"The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease","volume":"83","author":"Anders","year":"2013","journal-title":"Kidney Int."},{"key":"10.1016\/j.arr.2026.103390_bib7","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.bone.2012.05.015","article-title":"FGF23 acts directly on renal proximal tubules to induce phosphaturia through activation of the ERK1\/2\u2013SGK1 signaling pathway","volume":"51","author":"Andrukhova","year":"2012","journal-title":"Bone"},{"key":"10.1016\/j.arr.2026.103390_bib8","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2014.00189","article-title":"Skeletal muscle as a regulator of the longevity protein, Klotho","volume":"5","author":"Avin","year":"2014","journal-title":"Front. Physiol."},{"key":"10.1016\/j.arr.2026.103390_bib9","doi-asserted-by":"crossref","first-page":"4264","DOI":"10.1096\/fj.12-211631","article-title":"Promoter methylation confers kidney-specific expression of the Klotho gene","volume":"26","author":"Azuma","year":"2012","journal-title":"FASEB J."},{"key":"10.1016\/j.arr.2026.103390_bib10","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1161\/CIRCRESAHA.125.325515","article-title":"Emerging Technologies and Future Directions in Interorgan Crosstalk Cardiometabolic Research","volume":"136","author":"Bae","year":"2025","journal-title":"Circ. Res."},{"key":"10.1016\/j.arr.2026.103390_bib11","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1002\/ehf2.15345","article-title":"Interconnected Pathways and Emerging Therapies in Chronic Kidney Disease and Heart Failure: A Comprehensive Review","volume":"12","author":"Bauersachs","year":"2025","journal-title":"ESC Heart Fail."},{"key":"10.1016\/j.arr.2026.103390_bib12","doi-asserted-by":"crossref","first-page":"4634","DOI":"10.3390\/ijms20184634","article-title":"FGF23-Mediated Activation of Local RAAS Promotes Cardiac Hypertrophy and Fibrosis","volume":"20","author":"B\u00f6ckmann","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.arr.2026.103390_bib13","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1471-2369-14-56","article-title":"Indoxyl sulfate, a uremic toxin, downregulates renal expression of Nrf2 through activation of NF-\u03baB","volume":"14","author":"Bolati","year":"2013","journal-title":"BMC Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib14","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1146\/annurev-nutr-071816-064800","article-title":"Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis","volume":"38","author":"BonDurant","year":"2018","journal-title":"Annu. Rev. Nutr."},{"key":"10.1016\/j.arr.2026.103390_bib15","doi-asserted-by":"crossref","DOI":"10.1186\/s13613-024-01377-0","article-title":"Organ crosstalk and dysfunction in sepsis","volume":"14","author":"Borges","year":"2024","journal-title":"Ann. Intensive Care"},{"key":"10.1016\/j.arr.2026.103390_bib16","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.atherosclerosis.2015.08.017","article-title":"Soluble klotho and mortality: The Ludwigshafen Risk and Cardiovascular Health Study","volume":"242","author":"Brandenburg","year":"2015","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.arr.2026.103390_bib17","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2020.00560","article-title":"Klotho, Aging, and the Failing Kidney","volume":"11","author":"Buchanan","year":"2020","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"10.1016\/j.arr.2026.103390_bib18","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.2337\/db06-1491","article-title":"Metabolic Endotoxemia Initiates Obesity and Insulin Resistance","volume":"56","author":"Cani","year":"2007","journal-title":"Diabetes"},{"key":"10.1016\/j.arr.2026.103390_bib19","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2021.815796","article-title":"Natriuretic Peptides and Blood Pressure Homeostasis: Implications for MANP, a Novel Guanylyl Cyclase a Receptor Activator for Hypertension","volume":"12","author":"Cannone","year":"2022","journal-title":"Front. Physiol."},{"key":"10.1016\/j.arr.2026.103390_bib20","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/nyas.14217","article-title":"Effects of sympathetic modulation in metabolic disease","volume":"1454","author":"Carnagarin","year":"2019","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.arr.2026.103390_bib21","doi-asserted-by":"crossref","DOI":"10.1016\/j.labinv.2023.100178","article-title":"Pathophysiologic Implications and Therapeutic Approach of Klotho in Chronic Kidney Disease: A Systematic Review","volume":"103","author":"Castillo","year":"2023","journal-title":"Lab. Investig."},{"key":"10.1016\/j.arr.2026.103390_bib22","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/oby.22344","article-title":"Pegbelfermin (BMS-986036), PEGylated FGF21, in Patients with Obesity and Type 2 Diabetes: Results from a Randomized Phase 2 Study","volume":"27","author":"Charles","year":"2019","journal-title":"Obesity"},{"key":"10.1016\/j.arr.2026.103390_bib23","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1093\/gerona\/glz061","article-title":"Klotho: An Elephant in Aging Research","volume":"74","author":"Cheikhi","year":"2019","journal-title":"J. Gerontol. Ser. A"},{"key":"10.1016\/j.arr.2026.103390_bib24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s12031-017-1011-0","article-title":"Activation of the Anti-Aging and Cognition-Enhancing Gene Klotho by CRISPR-dCas9 Transcriptional Effector Complex","volume":"64","author":"Chen","year":"2018","journal-title":"J. Mol. Neurosci."},{"key":"10.1016\/j.arr.2026.103390_bib25","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"},{"key":"10.1016\/j.arr.2026.103390_bib26","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/s41586-023-06155-9","article-title":"Structural basis for FGF hormone signalling","volume":"618","author":"Chen","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.arr.2026.103390_bib27","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s00240-025-01836-8","article-title":"Assessing causal associations of FGF23 and \u03b1-Klotho with urolithiasis using Mendelian randomization analysis","volume":"53","author":"Chen","year":"2025","journal-title":"Urolithiasis"},{"key":"10.1016\/j.arr.2026.103390_bib28","doi-asserted-by":"crossref","first-page":"F327","DOI":"10.1152\/ajprenal.00115.2024","article-title":"Update: the role of epigenetics in the metabolic memory of diabetic complications","volume":"327","author":"Chen","year":"2024","journal-title":"Am. J. Physiol. -Ren. Physiol."},{"key":"10.1016\/j.arr.2026.103390_bib29","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3390\/biom12010070","article-title":"Association between Soluble \u03b1-Klotho Protein and Metabolic Syndrome in the Adult Population","volume":"12","author":"Cheng","year":"2022","journal-title":"Biomolecules"},{"key":"10.1016\/j.arr.2026.103390_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.aohep.2023.101125","article-title":"Association between klotho and non-alcoholic fatty liver disease and liver fibrosis based on the NHANES 2007\u20132016","volume":"28","author":"Chi","year":"2023","journal-title":"Ann. Hepatol."},{"key":"10.1016\/j.arr.2026.103390_bib31","doi-asserted-by":"crossref","DOI":"10.1093\/eurheartj\/ehaf784.3463","article-title":"The evolving burden of cardiovascular-kidney-liver-metabolic diseases: trends from 1990 to 2050","volume":"46","author":"Chong","year":"2025","journal-title":"Eur. Heart J."},{"key":"10.1016\/j.arr.2026.103390_bib32","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0176817","article-title":"\u03b1-Klotho expression determines nitric oxide synthesis in response to FGF-23 in human aortic endothelial cells","volume":"12","author":"Chung","year":"2017","journal-title":"PLoS. One"},{"key":"10.1016\/j.arr.2026.103390_bib33","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1038\/s41591-024-03015-5","article-title":"Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial","volume":"30","author":"Colhoun","year":"2024","journal-title":"Nat. Med."},{"key":"10.1016\/j.arr.2026.103390_bib34","doi-asserted-by":"crossref","first-page":"17587","DOI":"10.1038\/s41598-022-22123-1","article-title":"A systematic review and meta-analysis demonstrating Klotho as an emerging exerkine","volume":"12","author":"Corr\u00eaa","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.arr.2026.103390_bib35","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2017.00323","article-title":"New Insights into the Mechanism of Action of Soluble Klotho","volume":"8","author":"Dalton","year":"2017","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"10.1016\/j.arr.2026.103390_bib36","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1097\/HCO.0000000000000728","article-title":"Role of epigenetic mechanisms regulated by enhancers and long noncoding RNAs in cardiovascular disease","volume":"35","author":"Das","year":"2020","journal-title":"Curr. Opin. Cardiol."},{"key":"10.1016\/j.arr.2026.103390_bib37","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s40620-020-00842-w","article-title":"Renal dysfunction in cardiovascular diseases and its consequences","volume":"34","author":"Deferrari","year":"2021","journal-title":"J. Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib38","doi-asserted-by":"crossref","first-page":"8655","DOI":"10.1074\/jbc.M110.174037","article-title":"Klotho Inhibits Transforming Growth Factor-\u03b21 (TGF-\u03b21) Signaling and Suppresses Renal Fibrosis and Cancer Metastasis in Mice","volume":"286","author":"Doi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.arr.2026.103390_bib39","doi-asserted-by":"crossref","first-page":"239","DOI":"10.3390\/antiox12020239","article-title":"Klotho, Oxidative Stress, and Mitochondrial Damage in Kidney Disease","volume":"12","author":"Donate-Correa","year":"2023","journal-title":"Antioxidants"},{"key":"10.1016\/j.arr.2026.103390_bib40","doi-asserted-by":"crossref","unstructured":"Donate-Correa, J., Ferri, C.M., Mora-Fern\u00e1ndez, C., Gonz\u00e1lez-Luis, A., Navarro-Gonz\u00e1lez, J.F., P\u00e9rez-Delgado, N., 2024. Pentoxifylline Ameliorates Subclinical Atherosclerosis Progression in Patients with Type 2 Diabetes and Chronic Kidney Disease: A Randomized Pilot Trial. https:\/\/doi.org\/10.21203\/rs.3.rs-4599387\/v1.","DOI":"10.21203\/rs.3.rs-4599387\/v1"},{"key":"10.1016\/j.arr.2026.103390_bib41","article-title":"The Effect of FGF23 on Cardiac Hypertrophy Is Not Mediated by Systemic Renin-Angiotensin- Aldosterone System in Hemodialysis","volume":"9","author":"D\u00f6rr","year":"2022","journal-title":"Front. Med. (Lausanne)."},{"key":"10.1016\/j.arr.2026.103390_bib42","doi-asserted-by":"crossref","first-page":"341","DOI":"10.18388\/abp.2018_2635","article-title":"Crosstalk between TGF-\u03b2 and WNT signalling pathways during cardiac fibrogenesis","volume":"65","author":"Dzia\u0142o","year":"2018","journal-title":"Acta Biochim. Pol."},{"key":"10.1016\/j.arr.2026.103390_bib43","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1053\/j.ajkd.2024.02.008","article-title":"Klotho and Clinical Outcomes in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study","volume":"84","author":"Edmonston","year":"2024","journal-title":"Am. J. Kidney Dis."},{"key":"10.1016\/j.arr.2026.103390_bib44","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41569-023-00903-0","article-title":"FGF23 and klotho at the intersection of kidney and cardiovascular disease","volume":"21","author":"Edmonston","year":"2024","journal-title":"Nat. Rev. Cardiol."},{"key":"10.1016\/j.arr.2026.103390_bib45","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-025-65995-3","article-title":"A modular strategy for extracellular vesicle-mediated CRISPR-Cas9 delivery through aptamer-based loading and UV-activated cargo release","volume":"16","author":"Elsharkasy","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.arr.2026.103390_bib46","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.3390\/jcm11092415","article-title":"References Values of Soluble \u03b1-Klotho Serum Levels Using an Enzyme-Linked Immunosorbent Assay in Healthy Adults Aged 18\u201385 Years","volume":"11","author":"Espuch-Oliver","year":"2022","journal-title":"J. Clin. Med."},{"key":"10.1016\/j.arr.2026.103390_bib47","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1172\/JCI46122","article-title":"FGF23 induces left ventricular hypertrophy","volume":"121","author":"Faul","year":"2011","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.arr.2026.103390_bib48","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.2337\/db10-0193","article-title":"Obesity Is a Fibroblast Growth Factor 21 (FGF21)-Resistant State","volume":"59","author":"Fisher","year":"2010","journal-title":"Diabetes"},{"issue":"1","key":"10.1016\/j.arr.2026.103390_bib49","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3390\/pharmaceutics14010011","article-title":"Klotho and Mesenchymal Stem Cells: A Review on Cell and Gene Therapy for Chronic Kidney Disease and Acute Kidney Disease","volume":"14","author":"Franco","year":"2022","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.arr.2026.103390_bib50","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.kint.2025.01.024","article-title":"Fibroblast growth factor 23 and fibroblast growth factor receptor 4 promote cardiac metabolic remodeling in chronic kidney disease","volume":"107","author":"Fuchs","year":"2025","journal-title":"Kidney Int."},{"key":"10.1016\/j.arr.2026.103390_bib51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4061\/2011\/975782","article-title":"Cardiovascular and Renal Links along the Cardiorenal Continuum","volume":"2011","author":"Garc\u00eda-Donaire","year":"2011","journal-title":"Int. J. Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib52","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/s41574-020-0386-0","article-title":"The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic","volume":"16","author":"Geng","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.arr.2026.103390_bib53","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1093\/hmg\/ddab263","article-title":"GWAS meta-analysis followed by Mendelian randomization revealed potential control mechanisms for circulating \u03b1-Klotho levels","volume":"31","author":"Gergei","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.arr.2026.103390_bib54","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s43556-025-00253-y","article-title":"Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases","volume":"6","author":"Hajare","year":"2025","journal-title":"Mol. Biomed."},{"key":"10.1016\/j.arr.2026.103390_bib55","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1210\/en.2010-1262","article-title":"Lack of Overt FGF21 Resistance in Two Mouse Models of Obesity and Insulin Resistance","volume":"153","author":"Hale","year":"2012","journal-title":"Endocrinology"},{"key":"10.1016\/j.arr.2026.103390_bib56","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1161\/HYPERTENSIONAHA.120.14642","article-title":"Epigenetic Regulation of KL (Klotho) via H3K27me3 (Histone 3 Lysine [K] 27 Trimethylation) in Renal Tubule Cells","volume":"75","author":"Han","year":"2020","journal-title":"Hypertension"},{"key":"10.1016\/j.arr.2026.103390_bib57","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1146\/annurev-nutr-071812-161148","article-title":"AMP-Activated Protein Kinase: Maintaining Energy Homeostasis at the Cellular and Whole-Body Levels","volume":"34","author":"Hardie","year":"2014","journal-title":"Annu. Rev. Nutr."},{"key":"10.1016\/j.arr.2026.103390_bib58","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1073\/pnas.0611079104","article-title":"Amelioration of progressive renal injury by genetic manipulation of Klotho gene","volume":"104","author":"Haruna","year":"2007","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.arr.2026.103390_bib59","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2020.601349","article-title":"FGF19 and FGF21 for the Treatment of NASH\u2014Two Sides of the Same Coin? Differential and Overlapping Effects of FGF19 and FGF21 From Mice to Human","volume":"11","author":"Henriksson","year":"2020","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"10.1016\/j.arr.2026.103390_bib60","doi-asserted-by":"crossref","first-page":"R23","DOI":"10.1530\/JME-20-0178","article-title":"FGF23 signalling and physiology","volume":"66","author":"Ho","year":"2021","journal-title":"J. Mol. Endocrinol."},{"key":"10.1016\/j.arr.2026.103390_bib61","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.arr.2026.103390_bib62","doi-asserted-by":"crossref","unstructured":"Hu, M.C., Kuro-o, M., Moe, O.W., 2012. Secreted Klotho and Chronic Kidney Disease. pp. 126\u2013157. https:\/\/doi.org\/10.1007\/978-1-4614-0887-1_9.","DOI":"10.1007\/978-1-4614-0887-1_9"},{"key":"10.1016\/j.arr.2026.103390_bib63","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.semnephrol.2012.12.013","article-title":"Renal and Extrarenal Actions of Klotho","volume":"33","author":"Hu","year":"2013","journal-title":"Semin. Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib64","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1681\/ASN.2014050465","article-title":"Klotho and Phosphate Are Modulators of Pathologic Uremic Cardiac Remodeling","volume":"26","author":"Hu","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib65","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.kint.2016.10.034","article-title":"Recombinant \u03b1-Klotho may be prophylactic and therapeutic for acute to chronic kidney disease progression and uremic cardiomyopathy","volume":"91","author":"Hu","year":"2017","journal-title":"Kidney Int."},{"key":"10.1016\/j.arr.2026.103390_bib66","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00424-018-2238-5","article-title":"Role of \u03b1Klotho and FGF23 in regulation of type II Na-dependent phosphate co-transporters","volume":"471","author":"Hu","year":"2019","journal-title":"Pflug. Arch."},{"key":"10.1016\/j.arr.2026.103390_bib67","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."},{"key":"10.1016\/j.arr.2026.103390_bib68","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1146\/annurev-physiol-030212-183727","article-title":"Fibroblast Growth Factor 23 and Klotho: Physiology and Pathophysiology of an Endocrine Network of Mineral Metabolism","volume":"75","author":"Hu","year":"2013","journal-title":"Annu. Rev. Physiol."},{"key":"10.1016\/j.arr.2026.103390_bib69","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1007\/s11154-021-09661-1","article-title":"Beta-klotho in type 2 diabetes mellitus: From pathophysiology to therapeutic strategies","volume":"22","author":"Hua","year":"2021","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"10.1016\/j.arr.2026.103390_bib70","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.jhep.2011.03.005","article-title":"What is the long-term outcome of the liver allograft?","volume":"55","author":"H\u00fcbscher","year":"2011","journal-title":"J. Hepatol."},{"key":"10.1016\/j.arr.2026.103390_bib71","doi-asserted-by":"crossref","first-page":"iv6","DOI":"10.1093\/ndt\/gfs426","article-title":"Klotho, phosphate and inflammation\/ageing in chronic kidney disease","volume":"27","author":"Izquierdo","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"10.1016\/j.arr.2026.103390_bib72","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0245614","article-title":"A novel antibody for the detection of alternatively spliced secreted KLOTHO isoform in human plasma","volume":"16","author":"Jadhav","year":"2021","journal-title":"PLoS. One"},{"key":"10.1016\/j.arr.2026.103390_bib73","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1172\/JCI29126","article-title":"Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome","volume":"116","author":"Kadowaki","year":"2006","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.arr.2026.103390_bib74","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.118644","article-title":"Epigenetic and non-epigenetic regulation of Klotho in kidney disease","volume":"264","author":"Kale","year":"2021","journal-title":"Life Sci."},{"key":"10.1016\/j.arr.2026.103390_bib75","doi-asserted-by":"crossref","DOI":"10.1093\/ckj\/sfae255","article-title":"The association between klotho and kidney and cardiovascular outcomes: a comprehensive systematic review and meta-analysis","volume":"17","author":"Kanbay","year":"2024","journal-title":"Clin. Kidney J."},{"key":"10.1016\/j.arr.2026.103390_bib76","doi-asserted-by":"crossref","DOI":"10.1093\/ckj\/sfad276","article-title":"Klotho: a potential therapeutic target in aging and neurodegeneration beyond chronic kidney disease\u2014a comprehensive review from the ERA CKD-MBD working group","volume":"17","author":"Kanbay","year":"2024","journal-title":"Clin. Kidney J."},{"key":"10.1016\/j.arr.2026.103390_bib77","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1161\/HYPERTENSIONAHA.120.16635","article-title":"Role of Klotho in the Development of Essential Hypertension","volume":"77","author":"Kanbay","year":"2021","journal-title":"Hypertension"},{"key":"10.1016\/j.arr.2026.103390_bib78","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2022.992327","article-title":"Does Dapagliflozin influence arterial stiffness and levels of circulating anti-aging hormone soluble Klotho in people with type 2 diabetes and kidney disease? Results of a randomized parallel group clinical trial","volume":"9","author":"Karalliedde","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"10.1016\/j.arr.2026.103390_bib79","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.2215\/CJN.02700313","article-title":"Effect of Renin-Angiotensin System Blockade on Soluble Klotho in Patients with Type 2 Diabetes, Systolic Hypertension, and Albuminuria","volume":"8","author":"Karalliedde","year":"2013","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib80","doi-asserted-by":"crossref","DOI":"10.1172\/JCI134431","article-title":"Salt causes aging-associated hypertension via vascular Wnt5a under Klotho deficiency","author":"Kawarazaki","year":"2020","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.arr.2026.103390_bib81","doi-asserted-by":"crossref","DOI":"10.1097\/CRD.0000000000001203","article-title":"Fibroblast Growth Factor-23 and Cardiovascular Disease in Patients With Chronic Kidney Disease","author":"Kim","year":"2026","journal-title":"Cardiol. Rev."},{"key":"10.1016\/j.arr.2026.103390_bib82","doi-asserted-by":"crossref","DOI":"10.4110\/in.2018.18.e9","article-title":"Optimization of Cytokine Milieu to Reproduce Atopic Dermatitis-related Gene Expression in HaCaT Keratinocyte Cell Line","volume":"18","author":"Kim","year":"2018","journal-title":"Immune Netw."},{"key":"10.1016\/j.arr.2026.103390_bib83","article-title":"Low Klotho\/Fibroblast Growth Factor 23 Ratio Is an Independent Risk Factor for Renal Progression in Chronic Kidney Disease: Finding From KNOW-CKD","volume":"9","author":"Kim","year":"2022","journal-title":"Front. Med. (Lausanne)."},{"key":"10.1016\/j.arr.2026.103390_bib84","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12882-018-0851-3","article-title":"The association between soluble klotho and cardiovascular parameters in chronic kidney disease: results from the KNOW-CKD study","volume":"19","author":"Kim","year":"2018","journal-title":"BMC Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib85","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.jdiacomp.2016.03.006","article-title":"Decreased plasma \u03b1-Klotho predict progression of nephropathy with type 2 diabetic patients","volume":"30","author":"Kim","year":"2016","journal-title":"J. Diabetes Complicat."},{"key":"10.1016\/j.arr.2026.103390_bib86","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1007\/s11357-011-9315-4","article-title":"Promoter methylation and age-related downregulation of Klotho in rhesus monkey","volume":"34","author":"King","year":"2012","journal-title":"Age (Omaha)"},{"key":"10.1016\/j.arr.2026.103390_bib87","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.cmet.2019.01.004","article-title":"A Dozen Years of Discovery: Insights into the Physiology and Pharmacology of FGF21","volume":"29","author":"Kliewer","year":"2019","journal-title":"Cell. Metab."},{"key":"10.1016\/j.arr.2026.103390_bib88","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1097\/01.mnh.0000232885.81142.83","article-title":"Klotho as a regulator of fibroblast growth factor signaling and phosphate\/calcium metabolism","volume":"15","author":"Kuro-o","year":"2006","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"10.1016\/j.arr.2026.103390_bib89","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1038\/ki.2011.26","article-title":"Phosphate and Klotho","volume":"79","author":"Kuro-o","year":"2011","journal-title":"Kidney Int."},{"key":"10.1016\/j.arr.2026.103390_bib90","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."},{"key":"10.1016\/j.arr.2026.103390_bib91","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/ndt\/gfy126","article-title":"Klotho and endocrine fibroblast growth factors: markers of chronic kidney disease progression and cardiovascular complications?","volume":"34","author":"Kuro-o","year":"2019","journal-title":"Nephrol. Dial. Transplant."},{"key":"10.1016\/j.arr.2026.103390_bib92","doi-asserted-by":"crossref","first-page":"26687","DOI":"10.1074\/jbc.M704165200","article-title":"Tissue-specific Expression of \u03b2Klotho and Fibroblast Growth Factor (FGF) Receptor Isoforms Determines Metabolic Activity of FGF19 and FGF21","volume":"282","author":"Kurosu","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.arr.2026.103390_bib93","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12933-025-02615-w","article-title":"Predicting major adverse cardiac events in diabetes and chronic kidney disease: a machine learning study from the Silesia Diabetes-Heart Project","volume":"24","author":"Kwiendacz","year":"2025","journal-title":"Cardiovasc. Diabetol."},{"key":"10.1016\/j.arr.2026.103390_bib94","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1021\/acssynbio.8b00192","article-title":"Delivery of an Artificial Transcription Regulator dCas9-VPR by Extracellular Vesicles for Therapeutic Gene Activation","volume":"7","author":"Lain\u0161\u010dek","year":"2018","journal-title":"ACS Synth. Biol."},{"key":"10.1016\/j.arr.2026.103390_bib95","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1093\/ckj\/sfaa100","article-title":"Klotho: a link between cardiovascular and non-cardiovascular mortality","volume":"13","author":"Lanzani","year":"2020","journal-title":"Clin. Kidney J."},{"key":"10.1016\/j.arr.2026.103390_bib96","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1093\/gerona\/glz059","article-title":"Mechanistic target of rapamycin signaling in mouse models of accelerated aging","volume":"75","author":"Lee","year":"2020","journal-title":"J. Gerontol. Ser. A"},{"key":"10.1016\/j.arr.2026.103390_bib97","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2018.00278","article-title":"Paracrine Effects of FGF23 on the Heart","volume":"9","author":"Leifheit-Nestler","year":"2018","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"10.1016\/j.arr.2026.103390_bib98","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1093\/ndt\/gfy006","article-title":"Fibroblast growth factor 23 is induced by an activated renin\u2013angiotensin\u2013aldosterone system in cardiac myocytes and promotes the pro-fibrotic crosstalk between cardiac myocytes and fibroblasts","volume":"33","author":"Leifheit-Nestler","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"10.1016\/j.arr.2026.103390_bib99","doi-asserted-by":"crossref","DOI":"10.1016\/j.biomaterials.2024.122926","article-title":"Nanoparticle-mediated Klotho gene therapy prevents acute kidney injury to chronic kidney disease transition through regulating PPAR\u03b1 signaling in renal tubular epithelial cells","volume":"315","author":"Li","year":"2025","journal-title":"Biomaterials"},{"key":"10.1016\/j.arr.2026.103390_bib100","article-title":"Targeting the Wnt\/\u03b2-Catenin Signaling Pathway as a Potential Therapeutic Strategy in Renal Tubulointerstitial Fibrosis","volume":"12","author":"Li","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.arr.2026.103390_bib101","article-title":"Engineered Extracellular Vesicle-Delivered CRISPR\/CasRx as a Novel RNA Editing Tool","volume":"10","author":"Li","year":"2023","journal-title":"Adv. Sci."},{"key":"10.1016\/j.arr.2026.103390_bib102","article-title":"AMPK: a therapeutic target of heart failure\u2014not only metabolism regulation","volume":"39","author":"Li","year":"2019","journal-title":"Biosci. Rep."},{"key":"10.1016\/j.arr.2026.103390_bib103","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s00109-019-01759-z","article-title":"Klotho recovery by genistein via promoter histone acetylation and DNA demethylation mitigates renal fibrosis in mice","volume":"97","author":"Li","year":"2019","journal-title":"J. Mol. Med."},{"key":"10.1016\/j.arr.2026.103390_bib104","doi-asserted-by":"crossref","first-page":"796","DOI":"10.3390\/genes13050796","article-title":"Recent Advances in Epigenetics of Age-Related Kidney Diseases","volume":"13","author":"Liu","year":"2022","journal-title":"Genes"},{"key":"10.1016\/j.arr.2026.103390_bib105","doi-asserted-by":"crossref","first-page":"4647","DOI":"10.1038\/s41598-024-52701-4","article-title":"The optimal cut-off values of Klotho for predicting all-cause and cardiovascular mortality among chronic kidney disease: results from NHANES","volume":"14","author":"Liu","year":"2024","journal-title":"Sci. Rep."},{"key":"10.1016\/j.arr.2026.103390_bib106","first-page":"1","article-title":"The Prognostic Role of Klotho in Patients with Chronic Kidney Disease: A Systematic Review and Meta-analysis","volume":"2019","author":"Liu","year":"2019","journal-title":"Dis. Markers"},{"key":"10.1016\/j.arr.2026.103390_bib107","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s13148-026-02116-x","article-title":"DNMT inhibitor ameliorates hyperglycemia and renal inflammation partially via reversing hypermethylation-induced Klotho suppression in diabetic mice","volume":"18","author":"Liu","year":"2026","journal-title":"Clin. Epigenetics"},{"key":"10.1016\/j.arr.2026.103390_bib108","article-title":"U-shaped association between serum Klotho and all-cause mortality in US cardiovascular patients: a prospective cohort study","volume":"15","author":"Liu","year":"2024","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"10.1016\/j.arr.2026.103390_bib109","doi-asserted-by":"crossref","first-page":"183","DOI":"10.3350\/cmh.2021.0301","article-title":"Protective association of Klotho rs495392 gene polymorphism against hepatic steatosis in non-alcoholic fatty liver disease patients","volume":"28","author":"Liu","year":"2022","journal-title":"Clin. Mol. Hepatol."},{"key":"10.1016\/j.arr.2026.103390_bib110","doi-asserted-by":"crossref","DOI":"10.1016\/j.dsx.2023.102854","article-title":"Emerging role of \u03b1-Klotho in energy metabolism and cardiometabolic diseases","volume":"17","author":"Liu","year":"2023","journal-title":"Diabetes Metabolic Syndrome Clin. Res. Rev."},{"key":"10.1016\/j.arr.2026.103390_bib111","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1159\/000452880","article-title":"Klotho\/FGF23 Axis in Chronic Kidney Disease and Cardiovascular Disease","volume":"3","author":"Lu","year":"2017","journal-title":"Kidney Dis."},{"key":"10.1016\/j.arr.2026.103390_bib112","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2025.1703560","article-title":"Targeting the NLRP3 inflammasome in kidney disease: molecular mechanisms, pathogenic roles, and emerging small-molecule therapeutics","volume":"16","author":"Luo","year":"2025","journal-title":"Front. Immunol."},{"key":"10.1016\/j.arr.2026.103390_bib113","doi-asserted-by":"crossref","first-page":"9139","DOI":"10.18632\/aging.103183","article-title":"Klotho alleviates indoxyl sulfate-induced heart failure and kidney damage by promoting M2 macrophage polarization","volume":"12","author":"Lv","year":"2020","journal-title":"Aging"},{"key":"10.1016\/j.arr.2026.103390_bib114","doi-asserted-by":"crossref","first-page":"S51","DOI":"10.1097\/01.hjh.0000220407.84363.fb","article-title":"Angiotensin\u2013sympathetic system interactions in cardiovascular and metabolic disease","volume":"24","author":"Mancia","year":"2006","journal-title":"J. Hypertens."},{"key":"10.1016\/j.arr.2026.103390_bib115","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2018.01033","article-title":"Klotho and PPAR Gamma Activation Mediate the Renoprotective Effect of Losartan in the 5\/6 Nephrectomy Model","volume":"9","author":"Maquigussa","year":"2018","journal-title":"Front. Physiol."},{"key":"10.1016\/j.arr.2026.103390_bib116","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s12933-023-01937-x","article-title":"The cardio-renal-metabolic connection: a review of the evidence","volume":"22","author":"Marassi","year":"2023","journal-title":"Cardiovasc. Diabetol."},{"key":"10.1016\/j.arr.2026.103390_bib117","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1093\/ndt\/gfs138","article-title":"Randomized controlled trial of cholecalciferol supplementation in chronic kidney disease patients with hypovitaminosis D","volume":"27","author":"Marckmann","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"10.1016\/j.arr.2026.103390_bib118","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1016\/S0140-6736(25)01853-7","article-title":"Global, regional, and national burden of chronic kidney disease in adults, 1990\u20132023, and its attributable risk factors: a systematic analysis for the Global Burden of Disease Study 2023","volume":"406","author":"Mark","year":"2025","journal-title":"Lancet"},{"key":"10.1016\/j.arr.2026.103390_bib119","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.molmet.2017.03.009","article-title":"FGF21 resistance is not mediated by downregulation of beta-klotho expression in white adipose tissue","volume":"6","author":"Markan","year":"2017","journal-title":"Mol. Metab."},{"key":"10.1016\/j.arr.2026.103390_bib120","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1152\/physrev.00002.2011","article-title":"Regulation and Function of the FGF23\/Klotho Endocrine Pathways","volume":"92","author":"Martin","year":"2012","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.arr.2026.103390_bib121","doi-asserted-by":"crossref","first-page":"4875","DOI":"10.3390\/ijms25094875","article-title":"Non-Classical Effects of FGF23: Molecular and Clinical Features","volume":"25","author":"Mart\u00ednez-Heredia","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.arr.2026.103390_bib122","doi-asserted-by":"crossref","first-page":"H348","DOI":"10.1152\/ajpheart.00429.2013","article-title":"Aerobic exercise training increases plasma Klotho levels and reduces arterial stiffness in postmenopausal women","volume":"306","author":"Matsubara","year":"2014","journal-title":"Am. J. Physiol. -Heart Circ. Physiol."},{"key":"10.1016\/j.arr.2026.103390_bib123","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s12882-019-1391-1","article-title":"Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis","volume":"20","author":"Memmos","year":"2019","journal-title":"BMC Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib124","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.addr.2017.07.009","article-title":"Effects of Klotho on fibrosis and cancer: A renal focus on mechanisms and therapeutic strategies","volume":"121","author":"Mencke","year":"2017","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"10.1016\/j.arr.2026.103390_bib125","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.117608","article-title":"\u03b2-Klotho as novel therapeutic target in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A narrative review","volume":"180","author":"Meroni","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.arr.2026.103390_bib126","article-title":"The KLB rs12152703 variant confers protection against hepatic inflammation in patients with MASLD by boosting Klotho-beta expression","volume":"8","author":"Meroni","year":"2026","journal-title":"JHEP Rep."},{"key":"10.1016\/j.arr.2026.103390_bib127","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.14696","article-title":"Klotho retards renal fibrosis through targeting mitochondrial dysfunction and cellular senescence in renal tubular cells","volume":"9","author":"Miao","year":"2021","journal-title":"Physiol. Rep."},{"key":"10.1016\/j.arr.2026.103390_bib128","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41387-020-00144-x","article-title":"Exercise intensity regulates cytokine and klotho responses in men","volume":"11","author":"Middelbeek","year":"2021","journal-title":"Nutr. Diabetes"},{"key":"10.1016\/j.arr.2026.103390_bib129","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1161\/01.HYP.0000013734.33441.EA","article-title":"Vivo klotho Gene Transfer Ameliorates Angiotensin II-Induced Renal Damage","volume":"39","author":"Mitani","year":"2002","journal-title":"Hypertension"},{"key":"10.1016\/j.arr.2026.103390_bib130","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2022.113677","article-title":"Sodium-glucose co-transporter-2 inhibitors increase Klotho in patients with diabetic kidney disease: A clinical and experimental study","volume":"154","author":"Mora-Fern\u00e1ndez","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.arr.2026.103390_bib131","doi-asserted-by":"crossref","first-page":"H358","DOI":"10.1152\/ajpheart.00704.2012","article-title":"Natriuretic peptides and cGMP signaling control of energy homeostasis","volume":"304","author":"Moro","year":"2013","journal-title":"Am. J. Physiol. -Heart Circ. Physiol."},{"key":"10.1016\/j.arr.2026.103390_bib132","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.3390\/jcm14082833","article-title":"Cardiovascular\u2013Kidney\u2013Metabolic Syndrome: A New Paradigm in Clinical Medicine or Going Back to Basics?","volume":"14","author":"Mutruc","year":"2025","journal-title":"J. Clin. Med."},{"key":"10.1016\/j.arr.2026.103390_bib133","first-page":"40","article-title":"#451 The effects of early or late empagliflozin, liraglutide & combined therapy on the a-Klotho\/autophagy pathway in renal and pancreatic-\u00df cells in diabetic db\/db mice model","author":"Nakhoul","year":"2025","journal-title":"Nephrol. Dial. Transplant."},{"key":"10.1016\/j.arr.2026.103390_bib134","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2021.775029","article-title":"Fibroblast Growth Factor-23-Klotho Axis in Cardiorenal Syndrome: Mediators and Potential Therapeutic Targets","volume":"12","author":"Navarro-Garc\u00eda","year":"2021","journal-title":"Front. Physiol."},{"key":"10.1016\/j.arr.2026.103390_bib135","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1161\/CIR.0000000000001186","article-title":"A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association","volume":"148","author":"Ndumele","year":"2023","journal-title":"Circulation"},{"key":"10.1016\/j.arr.2026.103390_bib136","doi-asserted-by":"crossref","first-page":"162","DOI":"10.2215\/CJN.02840320","article-title":"Klotho in Clinical Nephrology","volume":"16","author":"Neyra","year":"2021","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib137","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/ckj\/sfz085","article-title":"Performance of soluble Klotho assays in clinical samples of kidney disease","volume":"13","author":"Neyra","year":"2020","journal-title":"Clin. Kidney J."},{"key":"10.1016\/j.arr.2026.103390_bib138","doi-asserted-by":"crossref","unstructured":"Neyra, J.A., Hu, M.C., 2016. \u03b1Klotho and Chronic Kidney Disease. pp. 257\u2013310. https:\/\/doi.org\/10.1016\/bs.vh.2016.02.007.","DOI":"10.1016\/bs.vh.2016.02.007"},{"key":"10.1016\/j.arr.2026.103390_bib139","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1161\/CIRCRESAHA.124.325488","article-title":"Renal-Cardiac Crosstalk in the Pathogenesis and Progression of Heart Failure","volume":"136","author":"Noels","year":"2025","journal-title":"Circ. Res."},{"key":"10.1016\/j.arr.2026.103390_bib140","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1084\/jem.20151570","article-title":"Immunometabolism governs dendritic cell and macrophage function","volume":"213","author":"O\u2019Neill","year":"2016","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.arr.2026.103390_bib141","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1161\/CIRCGENETICS.108.847814","article-title":"Vivo Genetic Evidence for Suppressing Vascular and Soft-Tissue Calcification Through the Reduction of Serum Phosphate Levels, Even in the Presence of High Serum Calcium and 1,25-Dihydroxyvitamin D Levels","volume":"2","author":"Ohnishi","year":"2009","journal-title":"Circ. Cardiovasc. Genet."},{"key":"10.1016\/j.arr.2026.103390_bib142","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2020.00064","article-title":"Organ System Crosstalk in Cardiometabolic Disease in the Age of Multimorbidity","volume":"7","author":"Oishi","year":"2020","journal-title":"Front. Cardiovasc. Med."},{"key":"10.1016\/j.arr.2026.103390_bib143","doi-asserted-by":"crossref","first-page":"6448","DOI":"10.1111\/jcmm.15293","article-title":"Klotho protein contributes to cardioprotection during ischaemia\/reperfusion injury","volume":"24","author":"Olejnik","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"10.1016\/j.arr.2026.103390_bib144","doi-asserted-by":"crossref","DOI":"10.1093\/eurjpc\/zwad125.273","article-title":"Klotho and FGF23 proteins levels and occurrence of myocardial infarction in patients with acute coronary syndrome","volume":"30","author":"Olejnik","year":"2023","journal-title":"Eur. J. Prev. Cardiol."},{"key":"10.1016\/j.arr.2026.103390_bib145","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-023-47686-5","article-title":"Klotho inhibits IGF1R\/PI3K\/AKT signalling pathway and protects the heart from oxidative stress during ischemia\/reperfusion injury","volume":"13","author":"Olejnik","year":"2023","journal-title":"Sci. Rep."},{"key":"10.1016\/j.arr.2026.103390_bib146","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2022\/7274858","article-title":"The Association of Obesity and the Antiaging Humoral Factor Klotho in Middle-Aged and Older Adults","volume":"2022","author":"Orces","year":"2022","journal-title":"Sci. World J."},{"key":"10.1016\/j.arr.2026.103390_bib147","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nrcardio.2016.98","article-title":"Myocardial energy depletion and dynamic systolic dysfunction in hypertrophic cardiomyopathy","volume":"13","author":"Ormerod","year":"2016","journal-title":"Nat. Rev. Cardiol."},{"key":"10.1016\/j.arr.2026.103390_bib148","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/s41591-025-04038-2","article-title":"Shared and specific blood biomarkers for multimorbidity","volume":"32","author":"Ornago","year":"2026","journal-title":"Nat. Med."},{"key":"10.1016\/j.arr.2026.103390_bib149","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.mce.2008.11.025","article-title":"Insulin\/IGF-1 and ROS signaling pathway cross-talk in aging and longevity determination","volume":"299","author":"Papaconstantinou","year":"2009","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.arr.2026.103390_bib150","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.3390\/metabo13111157","article-title":"The Longevity Protein Klotho: A Promising Tool to Monitor Lifestyle Improvements","volume":"13","author":"Paquette","year":"2023","journal-title":"Metabolites"},{"key":"10.1016\/j.arr.2026.103390_bib151","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0087102","article-title":"Novel Insights into the Cardio-Protective Effects of FGF21 in Lean and Obese Rat Hearts","volume":"9","author":"Patel","year":"2014","journal-title":"PLoS. One"},{"key":"10.1016\/j.arr.2026.103390_bib152","doi-asserted-by":"crossref","DOI":"10.1038\/tp.2016.135","article-title":"Klotho: a humeral mediator in CSF and plasma that influences longevity and susceptibility to multiple complex disorders, including depression","volume":"6","author":"Pavlatou","year":"2016","journal-title":"Transl. Psychiatry"},{"key":"10.1016\/j.arr.2026.103390_bib153","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.clinbiochem.2013.05.046","article-title":"Soluble serum Klotho levels in healthy subjects. Comparison of two different immunoassays","volume":"46","author":"Pedersen","year":"2013","journal-title":"Clin. Biochem."},{"key":"10.1016\/j.arr.2026.103390_bib154","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-30098-1","article-title":"Cardiovascular Interactions between Fibroblast Growth Factor-23 and Angiotensin II","volume":"8","author":"Pi","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.arr.2026.103390_bib155","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbrc.2023.149357","article-title":"The current and emerging Klotho-enhancement strategies","volume":"693","author":"Poursistany","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.arr.2026.103390_bib156","doi-asserted-by":"crossref","DOI":"10.3389\/fragi.2022.931331","article-title":"Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations","volume":"3","author":"Prud\u2019homme","year":"2022","journal-title":"Front. Aging"},{"key":"10.1016\/j.arr.2026.103390_bib157","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.3390\/cells13171413","article-title":"Anti-Inflammatory Role of the Klotho Protein and Relevance to Aging","volume":"13","author":"Prud\u2019homme","year":"2024","journal-title":"Cells"},{"key":"10.1016\/j.arr.2026.103390_bib158","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.yexcr.2012.02.027","article-title":"Role of FGF23 in vitamin D and phosphate metabolism: Implications in chronic kidney disease","volume":"318","author":"Quarles","year":"2012","journal-title":"Exp. Cell. Res."},{"key":"10.1016\/j.arr.2026.103390_bib159","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.freeradbiomed.2012.05.011","article-title":"Aldosterone, oxidative stress, and NF-\u03baB activation in hypertension-related cardiovascular and renal diseases","volume":"53","author":"Queisser","year":"2012","journal-title":"Free. Radic. Biol. Med."},{"key":"10.1016\/j.arr.2026.103390_bib160","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1111\/apt.70038","article-title":"Clinical Trial: A Phase 2b Study to Evaluate the Efficacy and Safety of MK-3655 in Individuals With Pre-Cirrhotic MASH","volume":"61","author":"Raji","year":"2025","journal-title":"Aliment. Pharmacol. Ther."},{"key":"10.1016\/j.arr.2026.103390_bib161","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nrendo.2009.196","article-title":"The FGF23\u2013Klotho axis: endocrine regulation of phosphate homeostasis","volume":"5","author":"Razzaque","year":"2009","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.arr.2026.103390_bib162","doi-asserted-by":"crossref","first-page":"8031","DOI":"10.3390\/ijms24098031","article-title":"Uremic Toxin Indoxyl Sulfate Promotes Macrophage-Associated Low-Grade Inflammation and Epithelial Cell Senescence","volume":"24","author":"Ribeiro","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.arr.2026.103390_bib163","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s10549-011-1824-4","article-title":"Epigenetic silencing of the tumor suppressor klotho in human breast cancer","volume":"133","author":"Rubinek","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"10.1016\/j.arr.2026.103390_bib164","doi-asserted-by":"crossref","DOI":"10.1038\/srep30484","article-title":"Fibroblast growth factor 21 reflects liver fat accumulation and dysregulation of signalling pathways in the liver of C57BL\/6J mice","volume":"6","author":"Rusli","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.arr.2026.103390_bib165","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2020.617842","article-title":"Shedding of Klotho: Functional Implications in Chronic Kidney Disease and Associated Vascular Disease","volume":"7","author":"Saar-Kovrov","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"10.1016\/j.arr.2026.103390_bib166","doi-asserted-by":"crossref","first-page":"4859","DOI":"10.1038\/s41467-018-07253-3","article-title":"Age-related declines in \u03b1-Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration","volume":"9","author":"Sahu","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.arr.2026.103390_bib167","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1016\/S0140-6736(18)31785-9","article-title":"Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial","volume":"392","author":"Sanyal","year":"2018","journal-title":"Lancet"},{"key":"10.1016\/j.arr.2026.103390_bib168","doi-asserted-by":"crossref","first-page":"F1641","DOI":"10.1152\/ajprenal.00460.2012","article-title":"Klotho protects against mouse renal fibrosis by inhibiting Wnt signaling","volume":"303","author":"Satoh","year":"2012","journal-title":"Am. J. Physiol. -Ren. Physiol."},{"key":"10.1016\/j.arr.2026.103390_bib169","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR Signaling in Growth, Metabolism, and Disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.arr.2026.103390_bib170","unstructured":"SELECT - Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity [WWW Document], n.d."},{"key":"10.1016\/j.arr.2026.103390_bib171","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.neulet.2013.10.058","article-title":"Klotho in the cerebrospinal fluid of adults with and without Alzheimer\u2019s disease","volume":"558","author":"Semba","year":"2014","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.arr.2026.103390_bib172","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2023.1213916","article-title":"Advances in genetic variation in metabolism-related fatty liver disease","volume":"14","author":"Shi","year":"2023","journal-title":"Front. Genet."},{"key":"10.1016\/j.arr.2026.103390_bib173","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-29396-5","article-title":"A systematic dissection of sequence elements determining \u03b2-Klotho and FGF interaction and signaling","volume":"8","author":"Shi","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.arr.2026.103390_bib174","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1159\/000324885","article-title":"Indoxyl Sulfate Downregulates Renal Expression of Klotho through Production of ROS and Activation of Nuclear Factor-\u0138B","volume":"33","author":"Shimizu","year":"2011","journal-title":"Am. J. Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib175","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1056\/NEJMra1011035","article-title":"Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease","volume":"371","author":"Shulman","year":"2014","journal-title":"New. Engl. J. Med."},{"key":"10.1016\/j.arr.2026.103390_bib176","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0093423","article-title":"Direct, Acute Effects of Klotho and FGF23 on Vascular Smooth Muscle and Endothelium","volume":"9","author":"Six","year":"2014","journal-title":"PLoS. One"},{"key":"10.1016\/j.arr.2026.103390_bib177","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.1007\/s00018-019-03241-y","article-title":"\u03b1Klotho\u2013FGF23 interactions and their role in kidney disease: a molecular insight","volume":"76","author":"Smith","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.arr.2026.103390_bib178","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2021.802541","article-title":"The Nuanced Metabolic Functions of Endogenous FGF21 Depend on the Nature of the Stimulus, Tissue Source, and Experimental Model","volume":"12","author":"Spann","year":"2022","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"10.1016\/j.arr.2026.103390_bib179","article-title":"Circulating \u03b1-Klotho Levels in Relation to Cardiovascular Diseases: A Mendelian Randomization Study","volume":"13","author":"Sun","year":"2022","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"10.1016\/j.arr.2026.103390_bib180","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1210\/me.2007-0313","article-title":"\u03b2Klotho Is Required for Fibroblast Growth Factor (FGF) 21 Signaling through FGF Receptor (FGFR) 1c and FGFR3c","volume":"22","author":"Suzuki","year":"2008","journal-title":"Mol. Endocrinol."},{"key":"10.1016\/j.arr.2026.103390_bib181","doi-asserted-by":"crossref","first-page":"H715","DOI":"10.1152\/ajpheart.00215.2017","article-title":"Pathophysiology of cardiorenal syndrome in patients with heart failure: potential therapeutic targets","volume":"313","author":"Takahama","year":"2017","journal-title":"Am. J. Physiol. -Heart Circ. Physiol."},{"key":"10.1016\/j.arr.2026.103390_bib182","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1161\/HYPERTENSIONAHA.118.11176","article-title":"Klotho Ameliorates Medullary Fibrosis and Pressure Natriuresis in Hypertensive Rat Kidneys","volume":"72","author":"Takenaka","year":"2018","journal-title":"Hypertension"},{"key":"10.1016\/j.arr.2026.103390_bib183","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.116922","article-title":"A systematic review of epigenetic interplay in kidney diseases: Crosstalk between long noncoding RNAs and methylation, acetylation of chromatin and histone","volume":"176","author":"Tan","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.arr.2026.103390_bib184","doi-asserted-by":"crossref","unstructured":"Tanasescu, M.-D., Rosu, A.-M., Minca, A., Rosu, A.-L., Grigorie, M.-M., Timofte, D., Ionescu, D., 2026. Metabolic Dysfunction at the Core: Revisiting the Overlap of Cardiovascular, Renal, Hepatic, and Endocrine Disorders. 16, 172. https:\/\/doi.org\/10.3390\/life16010172.","DOI":"10.3390\/life16010172"},{"key":"10.1016\/j.arr.2026.103390_bib185","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1180169","article-title":"Klotho\u2019s impact on diabetic nephropathy and its emerging connection to diabetic retinopathy","volume":"14","author":"Tang","year":"2023","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"10.1016\/j.arr.2026.103390_bib186","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1186\/s12944-024-02400-w","article-title":"Association of serum Klotho with the severity and mortality among adults with cardiovascular-kidney-metabolic syndrome","volume":"23","author":"Tang","year":"2024","journal-title":"Lipids Health Dis."},{"key":"10.1016\/j.arr.2026.103390_bib187","doi-asserted-by":"crossref","first-page":"213","DOI":"10.3390\/biom15020213","article-title":"From Cardiovascular-Kidney-Metabolic Syndrome to Cardiovascular-Renal-Hepatic-Metabolic Syndrome: Proposing an Expanded Framework","volume":"15","author":"Theodorakis","year":"2025","journal-title":"Biomolecules"},{"key":"10.1016\/j.arr.2026.103390_bib188","article-title":"GLP-1 Receptor Agonists Alleviate Diabetic Kidney Injury via \u03b2 -Klotho-Mediated Ferroptosis Inhibition","volume":"12","author":"Tian","year":"2025","journal-title":"Adv. Sci."},{"key":"10.1016\/j.arr.2026.103390_bib189","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1073\/pnas.0913986107","article-title":"Relevant use of Klotho in FGF19 subfamily signaling system in vivo","volume":"107","author":"Tomiyama","year":"2010","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.arr.2026.103390_bib190","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/nrneph.2010.55","article-title":"Metabolic memory and diabetic nephropathy: potential role for epigenetic mechanisms","volume":"6","author":"Tonna","year":"2010","journal-title":"Nat. Rev. Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib191","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/1475-2840-12-116","article-title":"Circulating alpha-klotho levels are not disturbed in patients with type 2 diabetes with and without macrovascular disease in the absence of nephropathy","volume":"12","author":"van Ark","year":"2013","journal-title":"Cardiovasc. Diabetol."},{"key":"10.1016\/j.arr.2026.103390_bib192","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1097\/MNH.0b013e328358c8d5","article-title":"CKD impairs barrier function and alters microbial flora of the intestine","volume":"21","author":"Vaziri","year":"2012","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"10.1016\/j.arr.2026.103390_bib193","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/path.6388","article-title":"Recombinant Klotho administration after myocardial infarction reduces ischaemic injury and arrhythmias by blocking intracellular calcium mishandling and <scp>CaMKII<\/scp> activation","volume":"265","author":"V\u00e1zquez-S\u00e1nchez","year":"2025","journal-title":"J. Pathol."},{"key":"10.1016\/j.arr.2026.103390_bib194","doi-asserted-by":"crossref","DOI":"10.1007\/s00018-019-03054-z","article-title":"Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia","author":"Voelkl","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.arr.2026.103390_bib195","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1002\/2211-5463.13872","article-title":"<scp>AMP<\/scp> -dependent kinase stimulates the expression of <scp>\u03b1Klotho<\/scp>.","volume":"14","author":"Vogt","year":"2024","journal-title":"FEBS Open. Bio"},{"key":"10.1016\/j.arr.2026.103390_bib196","doi-asserted-by":"crossref","DOI":"10.1016\/j.exger.2024.112643","article-title":"Sex differences in mortality risk and U-shaped relationship with klotho levels: A long-term cohort study","volume":"198","author":"Wang","year":"2024","journal-title":"Exp. Gerontol."},{"key":"10.1016\/j.arr.2026.103390_bib197","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s13105-023-00945-5","article-title":"Klotho improves cardiac fibrosis, inflammatory cytokines, ferroptosis, and oxidative stress in mice with myocardial infarction","volume":"79","author":"Wang","year":"2023","journal-title":"J. Physiol. Biochem."},{"key":"10.1016\/j.arr.2026.103390_bib198","article-title":"Association between serum Klotho levels and the prevalence of diabetes among adults in the United States","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"10.1016\/j.arr.2026.103390_bib199","article-title":"Effect of SGLT2 Inhibition (SGLT2i) on Blood and Urinary Biomarkers of Cardiovascular and Kidney Disease in Patients with Advanced Diabetic Kidney Disease (DKD)","volume":"36","author":"Wang","year":"2025","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib200","first-page":"1","article-title":"Correlation between Soluble \u03b1 -Klotho and Renal Function in Patients with Chronic Kidney Disease: A Review and Meta-Analysis","volume":"2018","author":"Wang","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"10.1016\/j.arr.2026.103390_bib201","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhou, C.J., Liu, Y., 2018b. Wnt Signaling in Kidney Development and Disease. pp. 181\u2013207. https:\/\/doi.org\/10.1016\/bs.pmbts.2017.11.019.","DOI":"10.1016\/bs.pmbts.2017.11.019"},{"key":"10.1016\/j.arr.2026.103390_bib202","doi-asserted-by":"crossref","DOI":"10.1016\/j.cyto.2024.156781","article-title":"The FGF23\u2013Klotho axis promotes microinflammation in chronic kidney disease","volume":"184","author":"Wang","year":"2024","journal-title":"Cytokine"},{"key":"10.1016\/j.arr.2026.103390_bib203","article-title":"Epigenetic Regulation of Hepatic Lipid Metabolism by DNA Methylation","volume":"10","author":"Wang","year":"2023","journal-title":"Adv. Sci."},{"key":"10.1016\/j.arr.2026.103390_bib204","article-title":"The core mechanism of hypertension-linked renal fibrosis: \u201cRAAS-ROS-inflammation-fibrosis\u201d axis","volume":"29","author":"Wang","year":"2026","journal-title":"iScience"},{"key":"10.1016\/j.arr.2026.103390_bib205","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1159\/000538510","article-title":"A Klotho-Based Machine Learning Model for Prediction of both Kidney and Cardiovascular Outcomes in Chronic Kidney Disease","volume":"10","author":"Wang","year":"2024","journal-title":"Kidney Dis."},{"key":"10.1016\/j.arr.2026.103390_bib206","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1161\/HYPERTENSIONAHA.109.134320","article-title":"Klotho Gene Delivery Prevents the Progression of Spontaneous Hypertension and Renal Damage","volume":"54","author":"Wang","year":"2009","journal-title":"Hypertension"},{"key":"10.1016\/j.arr.2026.103390_bib207","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1002\/jbmr.478","article-title":"FGF receptors control vitamin D and phosphate homeostasis by mediating renal FGF-23 signaling and regulating FGF-23 expression in bone","volume":"26","author":"W\u00f6hrle","year":"2011","journal-title":"J. Bone Mineral. Res."},{"key":"10.1016\/j.arr.2026.103390_bib208","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1069715","article-title":"The impact of SGLT2 inhibitors on \u03b1Klotho in renal MDCK and HK-2 cells","volume":"14","author":"Wolf","year":"2023","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"10.1016\/j.arr.2026.103390_bib209","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1152\/advan.00177.2016","article-title":"The renal and cardiovascular effects of natriuretic peptides","volume":"41","author":"Wong","year":"2017","journal-title":"Adv. Physiol. Educ."},{"key":"10.1016\/j.arr.2026.103390_bib210","doi-asserted-by":"crossref","first-page":"33304","DOI":"10.1074\/jbc.M803319200","article-title":"C-terminal Tail of FGF19 Determines Its Specificity toward Klotho Co-receptors","volume":"283","author":"Wu","year":"2008","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.arr.2026.103390_bib211","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.18632\/aging.100108","article-title":"Role of FGF19 induced FGFR4 activation in the regulation of glucose homeostasis","volume":"1","author":"Wu","year":"2009","journal-title":"Aging"},{"key":"10.1016\/j.arr.2026.103390_bib212","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.humpath.2012.07.023","article-title":"Epigenetic silencing of Klotho expression correlates with poor prognosis of human hepatocellular carcinoma","volume":"44","author":"Xie","year":"2013","journal-title":"Hum. Pathol."},{"key":"10.1016\/j.arr.2026.103390_bib213","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1038\/ncomms2240","article-title":"Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart","volume":"3","author":"Xie","year":"2012","journal-title":"Nat. Commun."},{"key":"10.1016\/j.arr.2026.103390_bib214","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1681\/ASN.2014040325","article-title":"Soluble Klotho Protects against Uremic Cardiomyopathy Independently of Fibroblast Growth Factor 23 and Phosphate","volume":"26","author":"Xie","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib215","doi-asserted-by":"crossref","first-page":"51264","DOI":"10.1021\/acsomega.4c07967","article-title":"The Long-Range Chromosomal Interaction Controlling Klotho Gene Expression in Human Chronic Kidney Disease","volume":"9","author":"Xu","year":"2024","journal-title":"ACS Omega"},{"key":"10.1016\/j.arr.2026.103390_bib216","doi-asserted-by":"crossref","DOI":"10.3892\/etm.2017.5287","article-title":"\u03b1-klotho and anemia in patients with chronic kidney disease patients: A new perspective (Review)","author":"Xu","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"10.1016\/j.arr.2026.103390_bib217","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.bone.2016.11.012","article-title":"Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho","volume":"100","author":"Yamada","year":"2017","journal-title":"Bone"},{"key":"10.1016\/j.arr.2026.103390_bib218","doi-asserted-by":"crossref","first-page":"E253","DOI":"10.1152\/ajpendo.00042.2026","article-title":"The role of \u03b2-Klotho in FGF signaling: from molecular insights to therapeutic innovations","volume":"331","author":"Yan","year":"2026","journal-title":"Am. J. Physiol. -Endocrinol. Metab."},{"key":"10.1016\/j.arr.2026.103390_bib219","article-title":"Differential Specificity of Endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in Complex with KLB","volume":"7","author":"Yang","year":"2012","journal-title":"PLoS. One"},{"key":"10.1016\/j.arr.2026.103390_bib220","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s12944-017-0447-0","article-title":"Klotho ameliorates oxidized low density lipoprotein (ox-LDL)-induced oxidative stress via regulating LOX-1 and PI3K\/Akt\/eNOS pathways","volume":"16","author":"Yao","year":"2017","journal-title":"Lipids Health Dis."},{"key":"10.1016\/j.arr.2026.103390_bib221","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.3350\/cmh.2024.0431","article-title":"Epidemiology of metabolic dysfunction-associated steatotic liver disease","volume":"31","author":"Younossi","year":"2025","journal-title":"Clin. Mol. Hepatol."},{"key":"10.1016\/j.arr.2026.103390_bib222","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1111\/apt.70020","article-title":"Addressing the High and Rising Global Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease ( <scp>MASLD<\/scp>) and Metabolic Dysfunction-Associated Steatohepatitis ( <scp>MASH<\/scp>): From the Growing Prevalence to Payors\u2019 Perspective","volume":"61","author":"Younossi","year":"2025","journal-title":"Aliment. Pharmacol. Ther."},{"key":"10.1016\/j.arr.2026.103390_bib223","doi-asserted-by":"crossref","first-page":"4851","DOI":"10.12659\/MSM.908038","article-title":"Klotho Inhibits Proliferation and Migration of Angiotensin II-Induced Vascular Smooth Muscle Cells (VSMCs) by Modulating NF-\u03baB p65, Akt, and Extracellular Signal Regulated Kinase (ERK) Signaling Activities","volume":"24","author":"Yu","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"10.1016\/j.arr.2026.103390_bib224","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/s41467-022-28096-z","article-title":"A Klotho-derived peptide protects against kidney fibrosis by targeting TGF-\u03b2 signaling","volume":"13","author":"Yuan","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.arr.2026.103390_bib225","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/s41392-022-01036-5","article-title":"Signaling pathways of chronic kidney diseases, implications for therapeutics","volume":"7","author":"Yuan","year":"2022","journal-title":"Signal. Transduct. Target. Ther."},{"key":"10.1016\/j.arr.2026.103390_bib226","doi-asserted-by":"crossref","DOI":"10.1007\/s13346-026-02166-x","article-title":"Hyperbranched poly(\u03b2-amino ester)s-mediated delivery of engineered Klotho mRNA rescues senescence and restores cellular homeostasis in aged and Klotho deficient iMSCs","author":"Zaidi","year":"2026","journal-title":"Drug. Deliv. Transl. Res."},{"key":"10.1016\/j.arr.2026.103390_bib227","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1186\/s12964-025-02308-7","article-title":"Mitochondrial dysfunction in the regulation of aging and aging-related diseases","volume":"23","author":"Zhang","year":"2025","journal-title":"Cell. Commun. Signal."},{"key":"10.1016\/j.arr.2026.103390_bib228","doi-asserted-by":"crossref","first-page":"420","DOI":"10.7150\/thno.89105","article-title":"Klotho-derived peptide 1 inhibits cellular senescence in the fibrotic kidney by restoring Klotho expression via posttranscriptional regulation","volume":"14","author":"Zhang","year":"2024","journal-title":"Theranostics"},{"key":"10.1016\/j.arr.2026.103390_bib229","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1186\/s12877-022-03265-3","article-title":"Association between testosterone and serum soluble \u03b1-klotho in U.S. males: a cross-sectional study","volume":"22","author":"Zhang","year":"2022","journal-title":"BMC Geriatr."},{"key":"10.1016\/j.arr.2026.103390_bib230","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1038\/s41401-025-01476-z","article-title":"Cardiorenal syndrome: clinical diagnosis, molecular mechanisms and therapeutic strategies","volume":"46","author":"Zhao","year":"2025","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.arr.2026.103390_bib231","article-title":"New insights into the role of Klotho in inflammation and fibrosis: molecular and cellular mechanisms","volume":"15","author":"Zhao","year":"2024","journal-title":"Front. Immunol."},{"key":"10.1016\/j.arr.2026.103390_bib232","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.2337\/db10-1262","article-title":"Klotho Depletion Contributes to Increased Inflammation in Kidney of the db\/db Mouse Model of Diabetes via RelA (Serine)536 Phosphorylation","volume":"60","author":"Zhao","year":"2011","journal-title":"Diabetes"},{"key":"10.1016\/j.arr.2026.103390_bib233","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.755366","article-title":"Klotho as Potential Autophagy Regulator and Therapeutic Target","volume":"12","author":"Zhou","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.arr.2026.103390_bib234","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1681\/ASN.2012080865","article-title":"Loss of Klotho Contributes to Kidney Injury by Derepression of Wnt\/\u03b2-Catenin Signaling","volume":"24","author":"Zhou","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib235","doi-asserted-by":"crossref","first-page":"385","DOI":"10.3390\/antiox12020385","article-title":"The Anti-Aging Hormone Klotho Promotes Retinal Pigment Epithelium Cell Viability and Metabolism by Activating the AMPK\/PGC-1\u03b1 Pathway","volume":"12","author":"Zhou","year":"2023","journal-title":"Antioxidants"},{"key":"10.1016\/j.arr.2026.103390_bib236","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2024.1390729","article-title":"Machine learning model for cardiovascular disease prediction in patients with chronic kidney disease","volume":"15","author":"Zhu","year":"2024","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"10.1016\/j.arr.2026.103390_bib237","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2022.103912","article-title":"Orally-active, clinically-translatable senolytics restore \u03b1-Klotho in mice and humans","volume":"77","author":"Zhu","year":"2022","journal-title":"EBioMedicine"},{"key":"10.1016\/j.arr.2026.103390_bib238","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1093\/ndt\/gfag022","article-title":"Kidney\u2013heart crosstalk: the extracellular vesicles connection","volume":"41","author":"Zoccali","year":"2026","journal-title":"Nephrol. Dial. Transplant."},{"key":"10.1016\/j.arr.2026.103390_bib239","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1186\/s12882-018-1094-z","article-title":"The role of klotho in chronic kidney disease","volume":"19","author":"Zou","year":"2018","journal-title":"BMC Nephrol."},{"key":"10.1016\/j.arr.2026.103390_bib240","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/nep.13472","article-title":"New insights into the role and mechanism of Wnt\/\u03b2-catenin signalling in kidney fibrosis","volume":"23","author":"Zuo","year":"2018","journal-title":"Nephrology"}],"container-title":["Ageing Research Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S156816372600382X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S156816372600382X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:25:35Z","timestamp":1791667535000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S156816372600382X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2027,1]]},"references-count":240,"alternative-id":["S156816372600382X"],"URL":"https:\/\/doi.org\/10.1016\/j.arr.2026.103390","relation":{},"ISSN":["1568-1637"],"issn-type":[{"value":"1568-1637","type":"print"}],"subject":[],"published":{"date-parts":[[2027,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Klotho within cardio-renal-hepatic-metabolic health: Integrating mineral metabolism, organ crosstalk, and therapeutic opportunities","name":"articletitle","label":"Article Title"},{"value":"Ageing Research Reviews","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.arr.2026.103390","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"103390"}}