{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:17:10Z","timestamp":1793121430678,"version":"4.5.0"},"reference-count":81,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006531","name":"Departament d&apos;Universitats, Recerca i Societat de la Informaci\u00f3","doi-asserted-by":"publisher","award":["2021SGR-00529"],"award-info":[{"award-number":["2021SGR-00529"]}],"id":[{"id":"10.13039\/501100006531","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Spain Ministry of Science and Innovation","doi-asserted-by":"publisher","award":["PID2020-116735RB-I00"],"award-info":[{"award-number":["PID2020-116735RB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2019-104034RB-100"],"award-info":[{"award-number":["PID2019-104034RB-100"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2022-14624OB-100"],"award-info":[{"award-number":["PID2022-14624OB-100"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Carlos III Health Institute","doi-asserted-by":"publisher","award":["RD21\/0017\/0008"],"award-info":[{"award-number":["RD21\/0017\/0008"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2025,4]]},"DOI":"10.1016\/j.ymthe.2025.02.030","type":"journal-article","created":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T11:06:55Z","timestamp":1740222415000},"page":"1449-1465","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"title":["Long-term effects of s-KL treatment in wild-type mice: Enhancing longevity, physical well-being, and neurological resilience"],"prefix":"10.1016","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6134-3141","authenticated-orcid":false,"given":"Joan","family":"Roig-Soriano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"Edo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Verd\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Mart\u00edn-Alonso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"S\u00e1nchez-de-Diego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rodriguez-Estevez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio L.","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela R.","family":"Abraham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assumpci\u00f3","family":"Bosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Ventura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryen A.","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pura","family":"Mu\u00f1oz-C\u00e1noves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Chill\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2025.02.030_bib1","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph17041439","article-title":"The Impact of Population Aging and Public Health Support on EU Labor Markets","volume":"17","author":"Cristea","year":"2020","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"10.1016\/j.ymthe.2025.02.030_bib2","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1093\/gerona\/glv130","article-title":"Aging, the Central Nervous System, and Mobility in Older Adults: Neural Mechanisms of Mobility Impairment","volume":"70","author":"Sorond","year":"2015","journal-title":"J. Gerontol. A. Biol. Sci. Med. Sci."},{"key":"10.1016\/j.ymthe.2025.02.030_bib3","doi-asserted-by":"crossref","first-page":"B209","DOI":"10.1093\/gerona\/56.5.B209","article-title":"Longitudinal muscle strength changes in older adults: influence of muscle mass, physical activity, and health","volume":"56","author":"Hughes","year":"2001","journal-title":"J. Gerontol. A. Biol. Sci. Med. Sci."},{"key":"10.1016\/j.ymthe.2025.02.030_bib4","first-page":"405","article-title":"Muscle tissue changes with aging","volume":"7","author":"Volpi","year":"2004","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"10.1016\/j.ymthe.2025.02.030_bib5","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1177\/1941738113502296","article-title":"Muscle changes in aging: understanding sarcopenia","volume":"6","author":"Siparsky","year":"2014","journal-title":"Sports Health"},{"key":"10.1016\/j.ymthe.2025.02.030_bib6","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/2044-5040-1-21","article-title":"Aberrant repair and fibrosis development in skeletal muscle","volume":"1","author":"Mann","year":"2011","journal-title":"Skelet. Muscle"},{"key":"10.1016\/j.ymthe.2025.02.030_bib7","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1016\/j.stem.2022.09.002","article-title":"Mitochondrial dynamics maintain muscle stem cell regenerative competence throughout adult life by regulating metabolism and mitophagy","volume":"29","author":"Hong","year":"2022","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ymthe.2025.02.030_bib8","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/d41586-022-04430-9","article-title":"Senescent cells damage the body throughout life","volume":"613","author":"Glass","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.02.030_bib9","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1359\/jbmr.040916","article-title":"Population-based study of age and sex differences in bone volumetric density, size, geometry, and structure at different skeletal sites","volume":"19","author":"Riggs","year":"2004","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.ymthe.2025.02.030_bib10","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S8756-3282(03)00199-6","article-title":"Bone development and age-related bone loss in male C57BL\/6J mice","volume":"33","author":"Ferguson","year":"2003","journal-title":"Bone"},{"key":"10.1016\/j.ymthe.2025.02.030_bib11","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/8756-3282(90)90052-Z","article-title":"Sex differences in age-related changes in vertebral body size, density and biomechanical competence in normal individuals","volume":"11","author":"Mosekilde","year":"1990","journal-title":"Bone"},{"key":"10.1016\/j.ymthe.2025.02.030_bib12","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21103679","article-title":"Molecular Basis of Bone Aging","volume":"21","author":"Corrado","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ymthe.2025.02.030_bib13","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.cytogfr.2019.09.001","article-title":"Collagen and non-collagenous proteins molecular crosstalk in the pathophysiology of osteoporosis","volume":"49","author":"Licini","year":"2019","journal-title":"Cytokine Growth Factor Rev."},{"key":"10.1016\/j.ymthe.2025.02.030_bib14","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nrneurol.2015.250","article-title":"Dementia: The rising global tide of cognitive impairment","volume":"12","author":"Hampel","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.ymthe.2025.02.030_bib15","doi-asserted-by":"crossref","DOI":"10.3390\/ijms222111489","article-title":"Adult Neurogenesis: A Story Ranging from Controversial New Neurogenic Areas and Human Adult Neurogenesis to Molecular Regulation","volume":"22","author":"Leal-Galicia","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ymthe.2025.02.030_bib16","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2021.646924","article-title":"Cellular Senescence in Brain Aging","volume":"13","author":"Sikora","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.ymthe.2025.02.030_bib17","doi-asserted-by":"crossref","first-page":"706","DOI":"10.3390\/ijms19030706","article-title":"Aged Mouse Cortical Microglia Display an Activation Profile Suggesting Immunotolerogenic Functions","volume":"19","author":"Zoller","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ymthe.2025.02.030_bib18","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3389\/fnagi.2019.00059","article-title":"Astrocyte Heterogeneity: Impact to Brain Aging and Disease","volume":"11","author":"Matias","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.ymthe.2025.02.030_bib19","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.tma.2019.01.002","article-title":"Senescence in aging and disorders of the central nervous system","volume":"3","author":"Swenson","year":"2019","journal-title":"Translational Med. Aging"},{"key":"10.1016\/j.ymthe.2025.02.030_bib20","doi-asserted-by":"crossref","first-page":"790","DOI":"10.3389\/fimmu.2019.00790","article-title":"Phagocytosis in the Brain: Homeostasis and Disease","volume":"10","author":"Galloway","year":"2019","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ymthe.2025.02.030_bib21","doi-asserted-by":"crossref","first-page":"5579","DOI":"10.1021\/bi500409n","article-title":"Identification of cleavage sites leading to the shed form of the anti-aging protein klotho","volume":"53","author":"Chen","year":"2014","journal-title":"Biochemistry"},{"key":"10.1016\/j.ymthe.2025.02.030_bib22","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"},{"key":"10.1016\/j.ymthe.2025.02.030_bib23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/S0014-5793(98)00127-6","article-title":"Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein","volume":"424","author":"Shiraki-Iida","year":"1998","journal-title":"FEBS Lett."},{"key":"10.1016\/j.ymthe.2025.02.030_bib24","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nature25451","article-title":"alpha-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling","volume":"553","author":"Chen","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.02.030_bib25","doi-asserted-by":"crossref","first-page":"6120","DOI":"10.1074\/jbc.C500457200","article-title":"Regulation of fibroblast growth factor-23 signaling by klotho","volume":"281","author":"Kurosu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymthe.2025.02.030_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2022.101766","article-title":"Aging-suppressor Klotho: Prospects in diagnostics and therapeutics","volume":"82","author":"Abraham","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.ymthe.2025.02.030_bib27","doi-asserted-by":"crossref","first-page":"4211","DOI":"10.1038\/s41598-023-31117-6","article-title":"Differential toxicity profile of secreted and processed alpha-Klotho expression over mineral metabolism and bone microstructure","volume":"13","author":"Roig-Soriano","year":"2023","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymthe.2025.02.030_bib28","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2121499119","article-title":"New intranasal and injectable gene therapy for healthy life extension","volume":"119","author":"Jaijyan","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2025.02.030_bib29","doi-asserted-by":"crossref","first-page":"23505","DOI":"10.1073\/pnas.1910073116","article-title":"A single combination gene therapy treats multiple age-related diseases","volume":"116","author":"Davidsohn","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2025.02.030_bib30","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1038\/s41467-018-05059-x","article-title":"AAVvector-mediated in vivo reprogramming into pluripotency","volume":"9","author":"Senis","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2025.02.030_bib31","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/emmm.201200245","article-title":"Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer","volume":"4","author":"Bernardes de Jesus","year":"2012","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.ymthe.2025.02.030_bib32","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/mt.2008.76","article-title":"Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection","volume":"16","author":"Zincarelli","year":"2008","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2025.02.030_bib33","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/j.celrep.2017.07.024","article-title":"Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and alpha-Synuclein Transgenic Mice","volume":"20","author":"Leon","year":"2017","journal-title":"Cell Rep."},{"key":"10.1016\/j.ymthe.2025.02.030_bib34","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/gt.2014.35","article-title":"rAAV9 combined with renal vein injection is optimal for kidney-targeted gene delivery: conclusion of a comparative study","volume":"21","author":"Rocca","year":"2014","journal-title":"Gene Ther."},{"key":"10.1016\/j.ymthe.2025.02.030_bib35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/978-1-4939-3271-9_10","article-title":"Controlling AAV Tropism in the Nervous System with Natural and Engineered Capsids","volume":"1382","author":"Castle","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.ymthe.2025.02.030_bib36","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.omtm.2020.12.006","article-title":"Rapid evolution of blood-brain-barrier-penetrating AAV capsids by RNA-driven biopanning","volume":"20","author":"Nonnenmacher","year":"2021","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.ymthe.2025.02.030_bib37","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/2211-5463.13029","article-title":"The CAG promoter maintains high-level transgene expression in HEK293 cells","volume":"11","author":"Dou","year":"2021","journal-title":"FEBS Open Bio"},{"key":"10.1016\/j.ymthe.2025.02.030_bib38","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.lfs.2015.10.025","article-title":"Men and mice: Relating their ages","volume":"152","author":"Dutta","year":"2016","journal-title":"Life Sci."},{"key":"10.1016\/j.ymthe.2025.02.030_bib39","first-page":"637","article-title":"The mouse in biomedical research. Chapt. 20 - Mouse Models in Aging Research","volume":"III","author":"Flurkey","year":"2007","journal-title":"Am. Coll. Lab. Anim. Med."},{"key":"10.1016\/j.ymthe.2025.02.030_bib40","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1089\/hum.2017.133","article-title":"Long-Term Sustained Effect of Liver-Targeted Adeno-Associated Virus Gene Therapy for Mitochondrial Neurogastrointestinal Encephalomyopathy","volume":"29","author":"Torres-Torronteras","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.ymthe.2025.02.030_bib41","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1182\/blood-2002-09-2889","article-title":"Sex significantly influences transduction of murine liver by recombinant adeno-associated viral vectors through an androgen-dependent pathway","volume":"102","author":"Davidoff","year":"2003","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2025.02.030_bib42","first-page":"586","article-title":"Progression of ulcerative dermatitis lesions in C57BL\/6Crl mice and the development of a scoring system for dermatitis lesions","volume":"51","author":"Hampton","year":"2012","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"10.1016\/j.ymthe.2025.02.030_bib43","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"},{"key":"10.1016\/j.ymthe.2025.02.030_bib44","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.celrep.2014.03.076","article-title":"Life extension factor klotho enhances cognition","volume":"7","author":"Dubal","year":"2014","journal-title":"Cell Rep."},{"key":"10.1016\/j.ymthe.2025.02.030_bib45","article-title":"Grip strength is potentially an early indicator of age-related decline in mice","volume":"6","author":"Ge","year":"2016","journal-title":"Pathobiol. Aging Age Relat. Dis."},{"key":"10.1016\/j.ymthe.2025.02.030_bib46","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24054651","article-title":"Sex Differences in Inflammation and Muscle Wasting in Aging and Disease","volume":"24","author":"Della Peruta","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ymthe.2025.02.030_bib47","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-46929-8","article-title":"Metabolomic Analysis of Skeletal Muscle in Aged Mice","volume":"9","author":"Uchitomi","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymthe.2025.02.030_bib48","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s10522-009-9260-0","article-title":"Delayed but excellent myogenic stem cell response of regenerating geriatric skeletal muscles in mice","volume":"11","author":"Shavlakadze","year":"2010","journal-title":"Biogerontology"},{"key":"10.1016\/j.ymthe.2025.02.030_bib49","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.61138","article-title":"The biphasic and age-dependent impact of klotho on hallmarks of aging and skeletal muscle function","volume":"10","author":"Clemens","year":"2021","journal-title":"Elife"},{"key":"10.1016\/j.ymthe.2025.02.030_bib50","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/s41586-022-05535-x","article-title":"Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration","volume":"613","author":"Moiseeva","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.02.030_bib51","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s10522-013-9447-2","article-title":"Decline in muscle strength and running endurance in klotho deficient C57BL\/6 mice","volume":"14","author":"Phelps","year":"2013","journal-title":"Biogerontology"},{"key":"10.1016\/j.ymthe.2025.02.030_bib52","doi-asserted-by":"crossref","first-page":"4859","DOI":"10.1038\/s41467-018-07253-3","article-title":"Age-related declines in alpha-Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration","volume":"9","author":"Sahu","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2025.02.030_bib53","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13395-018-0166-x","article-title":"Klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle","volume":"8","author":"Ahrens","year":"2018","journal-title":"Skelet. Muscle"},{"key":"10.1016\/j.ymthe.2025.02.030_bib54","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1113\/EP088142","article-title":"Modulation of Klotho expression in injured muscle perturbs Wnt signalling and influences the rate of muscle growth","volume":"105","author":"Welc","year":"2020","journal-title":"Exp. Physiol."},{"key":"10.1016\/j.ymthe.2025.02.030_bib55","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1359\/jbmr.070507","article-title":"Age-related changes in trabecular architecture differ in female and male C57BL\/6J mice","volume":"22","author":"Glatt","year":"2007","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.ymthe.2025.02.030_bib56","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/bs.acc.2021.06.001","article-title":"Advances in bone turnover markers","volume":"105","author":"Di Medio","year":"2021","journal-title":"Adv. Clin. Chem."},{"key":"10.1016\/j.ymthe.2025.02.030_bib57","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/j.1469-7580.2008.00859.x","article-title":"Histological and elemental analyses of impaired bone mineralization in klotho-deficient mice","volume":"212","author":"Suzuki","year":"2008","journal-title":"J. Anat."},{"key":"10.1016\/j.ymthe.2025.02.030_bib58","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.biomaterials.2015.01.004","article-title":"Bone micro-fragility caused by the mimetic aging processes in alpha-klotho deficient mice: in situ nanoindentation assessment of dilatational bands","volume":"47","author":"Maruyama","year":"2015","journal-title":"Biomaterials"},{"key":"10.1016\/j.ymthe.2025.02.030_bib59","article-title":"Klotho preservation via histone deacetylase inhibition attenuates chronic kidney disease-associated bone injury in mice","volume":"7","author":"Lin","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymthe.2025.02.030_bib60","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.bone.2013.08.008","article-title":"Altered distribution of bone matrix proteins and defective bone mineralization in klotho-deficient mice","volume":"57","author":"Sasaki","year":"2013","journal-title":"Bone"},{"key":"10.1016\/j.ymthe.2025.02.030_bib61","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/1873-3468.13613","article-title":"Soluble Klotho regulates bone differentiation by upregulating expression of the transcription factor EGR-1","volume":"594","author":"Toan","year":"2020","journal-title":"FEBS Lett."},{"key":"10.1016\/j.ymthe.2025.02.030_bib62","doi-asserted-by":"crossref","first-page":"898","DOI":"10.2741\/2730","article-title":"Regulation of bone development and maintenance by Runx2","volume":"13","author":"Komori","year":"2008","journal-title":"Front. Biosci."},{"key":"10.1016\/j.ymthe.2025.02.030_bib63","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1111\/jcmm.13192","article-title":"Age-dependent alterations in osteoblast and osteoclast activity in human cancellous bone","volume":"21","author":"Becerikli","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"10.1016\/j.ymthe.2025.02.030_bib64","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23052500","article-title":"Fibroblast Growth Factor 23 and Osteoporosis: Evidence from Bench to Bedside","volume":"23","author":"Sirikul","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ymthe.2025.02.030_bib65","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.neurobiolaging.2017.07.008","article-title":"Klotho regulates postnatal neurogenesis and protects against age-related spatial memory loss","volume":"59","author":"Laszczyk","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.ymthe.2025.02.030_bib66","doi-asserted-by":"crossref","first-page":"E11388","DOI":"10.1073\/pnas.1808609115","article-title":"Klotho controls the brain-immune system interface in the choroid plexus","volume":"115","author":"Zhu","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2025.02.030_bib67","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1093\/gerona\/glx248","article-title":"Local Klotho Enhances Neuronal Progenitor Proliferation in the Adult Hippocampus","volume":"74","author":"Salech","year":"2019","journal-title":"J. Gerontol. A. Biol. Sci. Med. Sci."},{"key":"10.1016\/j.ymthe.2025.02.030_bib68","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1093\/gerona\/gly261","article-title":"Klotho Deficiency Accelerates Stem Cells Aging by Impairing Telomerase Activity","volume":"74","author":"Ullah","year":"2019","journal-title":"J. Gerontol. A. Biol. Sci. Med. Sci."},{"key":"10.1016\/j.ymthe.2025.02.030_bib69","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12974-021-02104-3","article-title":"Senescent accelerated prone 8 (SAMP8) mice as a model of age dependent neuroinflammation","volume":"18","author":"Fernandez","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.ymthe.2025.02.030_bib70","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1111\/bpa.12456","article-title":"Microglia show altered morphology and reduced arborization in human brain during aging and Alzheimer's disease","volume":"27","author":"Davies","year":"2017","journal-title":"Brain Pathol."},{"key":"10.1016\/j.ymthe.2025.02.030_bib71","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.brainres.2011.03.039","article-title":"Limited hippocampal neurogenesis in SAMP8 mouse model of Alzheimer's disease","volume":"1389","author":"Gang","year":"2011","journal-title":"Brain Res."},{"key":"10.1016\/j.ymthe.2025.02.030_bib72","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13581","article-title":"AAV-mediated expression of secreted and transmembrane alphaKlotho isoforms rescues relevant aging hallmarks in senescent SAMP8 mice","volume":"21","author":"Roig-Soriano","year":"2022","journal-title":"Aging Cell"},{"key":"10.1016\/j.ymthe.2025.02.030_bib73","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s12020-009-9181-3","article-title":"Klotho suppresses TNF-alpha-induced expression of adhesion molecules in the endothelium and attenuates NF-kappaB activation","volume":"35","author":"Maekawa","year":"2009","journal-title":"Endocrine"},{"key":"10.1016\/j.ymthe.2025.02.030_bib74","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.ymthe.2025.02.030_bib75","doi-asserted-by":"crossref","DOI":"10.3390\/cells10051138","article-title":"Microglia in Aging and Alzheimer's Disease: A Comparative Species Review","volume":"10","author":"Edler","year":"2021","journal-title":"Cells"},{"key":"10.1016\/j.ymthe.2025.02.030_bib76","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.trci.2018.06.014","article-title":"Inflammation as a central mechanism in Alzheimer's disease","volume":"4","author":"Kinney","year":"2018","journal-title":"Alzheimers Dement (N Y)."},{"key":"10.1016\/j.ymthe.2025.02.030_bib77","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ibror.2018.12.002","article-title":"The impact of age on number and distribution of proliferating cells in subgranular zone in adult mouse brain","volume":"6","author":"Smith","year":"2019","journal-title":"IBRO Rep."},{"key":"10.1016\/j.ymthe.2025.02.030_bib78","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: An expanding universe","volume":"186","author":"Lopez-Otin","year":"2023","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2025.02.030_bib79","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/jnr.24419","article-title":"Microglial phagocytosis in aging and Alzheimer's disease","volume":"98","author":"Gabande-Rodriguez","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.ymthe.2025.02.030_bib80","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1038\/mp.2017.211","article-title":"Secreted alphaKlotho isoform protects against age-dependent memory deficits","volume":"23","author":"Masso","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.ymthe.2025.02.030_bib81","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1089\/hgtb.2014.120","article-title":"Development of a rapid, robust, and universal picogreen-based method to titer adeno-associated vectors","volume":"26","author":"Piedra","year":"2015","journal-title":"Hum. Gene Ther. Methods"}],"updated-by":[{"DOI":"10.1016\/j.ymthe.2025.06.046","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000}}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001625001200?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001625001200?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T20:42:37Z","timestamp":1762548157000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001625001200"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":81,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["S1525001625001200"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2025.02.030","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Long-term effects of s-KL treatment in wild-type mice: Enhancing longevity, physical well-being, and neurological resilience","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2025.02.030","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}]}}