{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:36:38Z","timestamp":1791246998048,"version":"4.1.0"},"posted":{"date-parts":[[2026,5,1]]},"group-title":"Neuroscience","reference-count":31,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["AG081981"],"award-info":[{"award-number":["AG081981"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["AG074552"],"award-info":[{"award-number":["AG074552"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001642","name":"Glenn Foundation for Medical Research","doi-asserted-by":"crossref","award":["AWD016559"],"award-info":[{"award-number":["AWD016559"]}],"id":[{"id":"10.13039\/100001642","id-type":"DOI","asserted-by":"crossref"}]},{"award":["Protein Folding Disease Initiative"],"award-info":[{"award-number":["Protein Folding Disease Initiative"]}],"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,1]]},"abstract":"<jats:title>Structured Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>INTRODUCTION<\/jats:title>\n                  <jats:p>Declines in function occur in both \u201cnormal\u201d aging (in the absence of disease) and age-related pathological contexts, like Alzheimer\u2019s disease (AD). Whether \u201canti-aging\u201d interventions (that extend lifespan) also promote cognitive function in aging and AD remains unexplored.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>We assessed the effect of acarbose (1000 ppm from 4 months of age) on spatial learning and memory using the Morris water maze in young adult (6 mo), mid-aged (12 mo), or aged (24 mo) cohorts of normal aging (Ntg-HET3) and AD-relevant (5xFAD-HET3) genetically heterogeneous mice.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>In mid-aged and aged Ntg-HET3 mice, acarbose treatment resulted in performance equivalent to young adults. Conversely, acarbose failed to ameliorate age-related deficits in 5xFAD-HET3 mice.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>This work demonstrates that anti-aging interventions can also promote cognitive longevity in normal aging. Further, it reinforces that AD is not simply accelerated aging and requires therapies beyond anti-aging interventions that target its unique molecular and cellular drivers.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.28.721469","type":"posted-content","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T19:40:18Z","timestamp":1777664418000},"source":"Crossref","is-referenced-by-count":1,"title":["Acarbose improves cognitive function in a mouse model of normal aging but not Alzheimer\u2019s disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5874-6572","authenticated-orcid":false,"given":"Shannon J.","family":"Moore","sequence":"first","affiliation":[{"name":"Molecular & Integrative Physiology"},{"name":"Neurology"},{"name":"Michigan Neuroscience Institute, University of Michigan Medical School, Ann Arbor, MI, 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey G.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Molecular & Integrative Physiology"},{"name":"Michigan Neuroscience Institute, University of Michigan Medical School, Ann Arbor, MI, 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026050512350742000_2026.04.28.721469v1.1","unstructured":"Vincent GK , Velkoff VA , U.S. Census Bureau. The next four decades : the older population in the United States : 2010 to 2050. Washington, D.C.: U.S. Dept. of Commerce, Economics and Statistics Administration, U.S. Census Bureau; 2010."},{"key":"2026050512350742000_2026.04.28.721469v1.2","doi-asserted-by":"publisher","DOI":"10.1093\/geront\/gnv130"},{"key":"2026050512350742000_2026.04.28.721469v1.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.12.5360"},{"key":"2026050512350742000_2026.04.28.721469v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.039"},{"key":"2026050512350742000_2026.04.28.721469v1.5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2007.00311.x"},{"key":"2026050512350742000_2026.04.28.721469v1.6","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s11357-008-9048-1","article-title":"Design of aging intervention studies: the NIA interventions testing program","volume":"30","year":"2008","journal-title":"Age (Dordr"},{"key":"2026050512350742000_2026.04.28.721469v1.7","doi-asserted-by":"crossref","unstructured":"Herrera JJ , Louzon S , Pifer K , Leander D , Merrihew GE , Park JH , et al. Acarbose has sex-dependent and -independent effects on age-related physical function, cardiac health, and lipid biology. JCI Insight. 2020;5.","DOI":"10.1172\/jci.insight.137474"},{"key":"2026050512350742000_2026.04.28.721469v1.8","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12898"},{"key":"2026050512350742000_2026.04.28.721469v1.9","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12590"},{"key":"2026050512350742000_2026.04.28.721469v1.10","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13653"},{"key":"2026050512350742000_2026.04.28.721469v1.11","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glz177"},{"key":"2026050512350742000_2026.04.28.721469v1.12","doi-asserted-by":"crossref","first-page":"e70255","DOI":"10.1111\/acel.70255","article-title":"Canagliflozin Reprograms the Aging Hippocampus in Genetically Diverse UM-HET3 Mice and Attenuates Alzheimer\u2019s-Like Pathology","volume":"24","year":"2025","journal-title":"Aging Cell"},{"key":"2026050512350742000_2026.04.28.721469v1.13","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"2026050512350742000_2026.04.28.721469v1.14","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828726f5"},{"key":"2026050512350742000_2026.04.28.721469v1.15","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.dadm.2017.04.001","article-title":"Severity of memory impairment in the elderly: Association with health care resource use and functional limitations in the United States","volume":"8","year":"2017","journal-title":"Alzheimers Dement (Amst"},{"key":"2026050512350742000_2026.04.28.721469v1.16","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291700034930"},{"key":"2026050512350742000_2026.04.28.721469v1.17","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200363100-00002"},{"key":"2026050512350742000_2026.04.28.721469v1.18","doi-asserted-by":"publisher","DOI":"10.1177\/019262339602400618"},{"key":"2026050512350742000_2026.04.28.721469v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2005.03.012"},{"key":"2026050512350742000_2026.04.28.721469v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2022.07.004"},{"key":"2026050512350742000_2026.04.28.721469v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2005.11.007"},{"key":"2026050512350742000_2026.04.28.721469v1.22","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12170"},{"key":"2026050512350742000_2026.04.28.721469v1.23","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1202-06.2006"},{"key":"2026050512350742000_2026.04.28.721469v1.24","doi-asserted-by":"crossref","first-page":"e13781","DOI":"10.1111\/acel.13781","article-title":"Age-related deficits in neuronal physiology and cognitive function are recapitulated in young mice overexpressing the L-type calcium channel, Ca(V) 1.3","volume":"22","year":"2023","journal-title":"Aging Cell"},{"key":"2026050512350742000_2026.04.28.721469v1.25","doi-asserted-by":"crossref","first-page":"100262","DOI":"10.1016\/j.ynstr.2020.100262","article-title":"Deficits across multiple behavioral domains align with susceptibility to stress in 129S1\/SvImJ mice","volume":"13","year":"2020","journal-title":"Neurobiol Stress"},{"key":"2026050512350742000_2026.04.28.721469v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.116"},{"key":"2026050512350742000_2026.04.28.721469v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3085"},{"key":"2026050512350742000_2026.04.28.721469v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3200"},{"key":"2026050512350742000_2026.04.28.721469v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"2026050512350742000_2026.04.28.721469v1.30","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.785276"},{"key":"2026050512350742000_2026.04.28.721469v1.31","first-page":"1569","article-title":"Acarbose ameliorates Western diet-induced metabolic and cognitive impairments in the 3xTg mouse model of Alzheimer\u2019s disease","volume":"47","year":"2025","journal-title":"Geroscience"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.28.721469","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T19:35:19Z","timestamp":1778009719000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.28.721469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":31,"URL":"https:\/\/doi.org\/10.64898\/2026.04.28.721469","relation":{},"subject":[],"published":{"date-parts":[[2026,5,1]]},"subtype":"preprint"}}