{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T20:24:49Z","timestamp":1750364689476,"version":"3.37.3"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RF1 AG054714","P30 014195"],"award-info":[{"award-number":["RF1 AG054714","P30 014195"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shiley-Marcos ADRC"},{"DOI":"10.13039\/100007557","name":"California Institute of Regenerative Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007557","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Helmsley Trust"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["GeroScience"],"published-print":{"date-parts":[[2021,2]]},"DOI":"10.1007\/s11357-020-00238-5","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T09:03:53Z","timestamp":1595495033000},"page":"353-365","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A chemical biology approach to identifying molecular pathways associated with aging"],"prefix":"10.1007","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4142-7054","authenticated-orcid":false,"given":"Antonio","family":"Currais","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Petrascheck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela","family":"Maher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Schubert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,23]]},"reference":[{"issue":"12","key":"238_CR1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027865","volume":"6","author":"Q Chen","year":"2011","unstructured":"Chen Q, Prior M, Dargusch R, Roberts A, Riek R, Eichmann C, et al. A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease. PLoS One. 2011;6(12):e27865.","journal-title":"PLoS One"},{"key":"238_CR2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.arr.2013.10.002","volume":"13","author":"XR Cheng","year":"2014","unstructured":"Cheng XR, Zhou WX, Zhang YX. The behavioral, pathological and therapeutic features of the senescence-accelerated mouse prone 8 strain as an Alzheimer\u2019s disease animal model. Ageing Res Rev. 2014;13:13\u201337.","journal-title":"Ageing Res Rev"},{"issue":"1","key":"238_CR3","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1021\/jm2012563","volume":"55","author":"C Chiruta","year":"2012","unstructured":"Chiruta C, Schubert D, Dargusch R, Maher P. Chemical modification of the multitarget neuroprotective compound fisetin. J Med Chem. 2012;55(1):378\u201389.","journal-title":"J Med Chem"},{"issue":"6","key":"238_CR4","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1111\/acel.12002","volume":"11","author":"A Currais","year":"2012","unstructured":"Currais A, Prior M, Lo D, Jolivalt C, Schubert D, Maher P. Diabetes exacerbates amyloid and neurovascular pathology in aging-accelerated mice. Aging Cell. 2012;11(6):1017\u201326.","journal-title":"Aging Cell"},{"issue":"11","key":"238_CR5","doi-asserted-by":"publisher","first-page":"937","DOI":"10.18632\/aging.100838","volume":"7","author":"A Currais","year":"2015","unstructured":"Currais A, Goldberg J, Farrokhi C, Chang M, Prior M, Dargusch R, et al. A comprehensive multiomics approach toward understanding the relationship between aging and dementia. Aging (Albany NY). 2015;7(11):937\u201355.","journal-title":"Aging (Albany NY)"},{"issue":"3","key":"238_CR6","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1093\/gerona\/glx104","volume":"73","author":"A Currais","year":"2018","unstructured":"Currais A, Farrokhi C, Dargusch R, Armando A, Quehenberger O, Schubert D, et al. Fisetin reduces the impact of aging on behavior and physiology in the rapidly aging SAMP8 mouse. J Gerontol A Biol Sci Med Sci. 2018;73(3):299\u2013307.","journal-title":"J Gerontol A Biol Sci Med Sci"},{"doi-asserted-by":"publisher","unstructured":"Currais, A., et al., Elevating acetyl-CoA levels reduces aspects of brain aging. E-Life, 2019. 8: p. pii: 47866. https:\/\/doi.org\/10.7554\/eLife.47866. [Epub ahead of print].","key":"238_CR7","DOI":"10.7554\/eLife.47866"},{"issue":"1","key":"238_CR8","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13195-017-0277-3","volume":"9","author":"D Daugherty","year":"2017","unstructured":"Daugherty D, Goldberg J, Fischer W, Dargusch R, Maher P, Schubert D. A novel Alzheimer\u2019s disease drug candidate targeting inflammation and fatty acid metabolism. Alzheimers Res Ther. 2017;9(1):50.","journal-title":"Alzheimers Res Ther"},{"issue":"1","key":"238_CR9","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/0006-8993(94)90334-4","volume":"652","author":"JB Davis","year":"1994","unstructured":"Davis JB, Maher P. Protein kinase C activation inhibits glutamate-induced cytotoxicity in a neuronal cell line. Brain Res. 1994;652(1):169\u201373.","journal-title":"Brain Res"},{"issue":"7","key":"238_CR10","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1093\/bioinformatics\/btp073","volume":"25","author":"JP de Magalhaes","year":"2009","unstructured":"de Magalhaes JP, Curado J, Church GM. Meta-analysis of age-related gene expression profiles identifies common signatures of aging. Bioinformatics. 2009;25(7):875\u201381.","journal-title":"Bioinformatics"},{"issue":"1","key":"238_CR11","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15\u201321.","journal-title":"Bioinformatics"},{"issue":"1","key":"238_CR12","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","volume":"30","author":"R Edgar","year":"2002","unstructured":"Edgar R, Domrachev M, Lash AE. Gene expression omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002;30(1):207\u201310.","journal-title":"Nucleic Acids Res"},{"key":"238_CR13","doi-asserted-by":"publisher","first-page":"e12715","DOI":"10.1111\/acel.12715","volume":"2","author":"J Goldberg","year":"2018","unstructured":"Goldberg J, et al. The mitochondrial ATP synthase is a shared drug target among aging and dementia. Aging Cell. 2018;2:e12715.","journal-title":"Aging Cell"},{"issue":"1","key":"238_CR14","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","volume":"4","author":"d W Huang","year":"2009","unstructured":"Huang d W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009a;4(1):44\u201357.","journal-title":"Nat Protoc"},{"issue":"1","key":"238_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nar\/gkn923","volume":"37","author":"d W Huang","year":"2009","unstructured":"Huang d W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009b;37(1):1\u201313.","journal-title":"Nucleic Acids Res"},{"key":"238_CR16","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.mito.2020.04.012","volume":"53","author":"H Li","year":"2020","unstructured":"Li H, Slone J, Huang T. The role of mitochondrial-related nuclear genes in age-related common disease. Mitochondrion. 2020;53:38\u201347.","journal-title":"Mitochondrion"},{"issue":"6","key":"238_CR17","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","volume":"153","author":"C Lopez-Otin","year":"2013","unstructured":"Lopez-Otin C, et al. The hallmarks of aging. Cell. 2013;153(6):1194\u2013217.","journal-title":"Cell"},{"issue":"10","key":"238_CR18","doi-asserted-by":"publisher","first-page":"4288","DOI":"10.1093\/nar\/gks042","volume":"40","author":"DJ McCarthy","year":"2012","unstructured":"McCarthy DJ, Chen Y, Smyth GK. Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res. 2012;40(10):4288\u201397.","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"238_CR19","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1016\/j.bbadis.2011.11.015","volume":"1822","author":"JE Morley","year":"2012","unstructured":"Morley JE, Armbrecht HJ, Farr SA, Kumar VB. The senescence accelerated mouse (SAMP8) as a model for oxidative stress and Alzheimer\u2019s disease. Biochim Biophys Acta. 2012;1822(5):650\u20136.","journal-title":"Biochim Biophys Acta"},{"issue":"3","key":"238_CR20","doi-asserted-by":"publisher","first-page":"354","DOI":"10.14336\/AD.2016.1022","volume":"8","author":"A Moskalev","year":"2017","unstructured":"Moskalev A, Chernyagina E, Kudryavtseva A, Shaposhnikov M. Geroprotectors: a unified concept and screening approaches. Aging Dis. 2017;8(3):354\u201363.","journal-title":"Aging Dis"},{"doi-asserted-by":"crossref","unstructured":"Mustafa, M.F., et al., Pathogenic mitochondria DNA mutations: current detection tools and interventions. Genes (Basel), 2020. 11(2).","key":"238_CR21","DOI":"10.3390\/genes11020192"},{"issue":"5","key":"238_CR22","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1083\/jcb.201010024","volume":"193","author":"CB Park","year":"2011","unstructured":"Park CB, Larsson NG. Mitochondrial DNA mutations in disease and aging. J Cell Biol. 2011;193(5):809\u201318.","journal-title":"J Cell Biol"},{"issue":"7","key":"238_CR23","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1021\/cn500051h","volume":"5","author":"M Prior","year":"2014","unstructured":"Prior M, Chiruta C, Currais A, Goldberg J, Ramsey J, Dargusch R, et al. Back to the future with phenotypic screening. ACS Chem Neurosci. 2014;5(7):503\u201313.","journal-title":"ACS Chem Neurosci"},{"issue":"6","key":"238_CR24","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1016\/j.jalz.2016.03.016","volume":"12","author":"M Prior","year":"2016","unstructured":"Prior M, Goldberg J, Chiruta C, Farrokhi C, Kopynets M, Roberts AJ, et al. Selecting for neurogenic potential as an alternative for Alzheimer\u2019s disease drug discovery. Alzheimers Dement. 2016;12(6):678\u201386.","journal-title":"Alzheimers Dement"},{"doi-asserted-by":"crossref","unstructured":"Rangaraju S, et al. Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality. Elife. 2015a;4.","key":"238_CR25","DOI":"10.7554\/eLife.08833"},{"key":"238_CR26","doi-asserted-by":"publisher","first-page":"e08833","DOI":"10.7554\/eLife.08833","volume":"4","author":"S Rangaraju","year":"2015","unstructured":"Rangaraju S, Solis GM, Thompson RC, Gomez-Amaro RL, Kurian L, Encalada SE, et al. Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality. Elife. 2015b;4:e08833.","journal-title":"Elife"},{"key":"238_CR27","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.jsbmb.2016.03.012","volume":"160","author":"BC Riedel","year":"2016","unstructured":"Riedel BC, Thompson PM, Brinton RD. Age, APOE and sex: triad of risk of Alzheimer\u2019s disease. J Steroid Biochem Mol Biol. 2016;160:134\u201347.","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"1","key":"238_CR28","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.jalz.2010.11.002","volume":"7","author":"WA Rocca","year":"2011","unstructured":"Rocca WA, Petersen RC, Knopman DS, Hebert LE, Evans DA, Hall KS, et al. Trends in the incidence and prevalence of Alzheimer\u2019s disease, dementia, and cognitive impairment in the United States. Alzheimers Dement. 2011;7(1):80\u201393.","journal-title":"Alzheimers Dement"},{"issue":"12","key":"238_CR29","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1016\/j.tips.2018.09.008","volume":"39","author":"D Schubert","year":"2018","unstructured":"Schubert D, Currais A, Goldberg J, Finley K, Petrascheck M, Maher P. Geroneuroprotectors: effective geroprotectors for the brain. Trends Pharmacol Sci. 2018;39(12):1004\u20137.","journal-title":"Trends Pharmacol Sci"},{"issue":"W1","key":"238_CR30","doi-asserted-by":"publisher","first-page":"W194","DOI":"10.1093\/nar\/gkw266","volume":"44","author":"AA Sergushichev","year":"2016","unstructured":"Sergushichev AA, Loboda AA, Jha AK, Vincent EE, Driggers EM, Jones RG, et al. GAM: a web-service for integrated transcriptional and metabolic network analysis. Nucleic Acids Res. 2016;44(W1):W194\u2013200.","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"238_CR31","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498\u2013504.","journal-title":"Genome Res"},{"issue":"1","key":"238_CR32","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S0896-6273(03)00367-2","volume":"39","author":"T Soucek","year":"2003","unstructured":"Soucek T, Cumming R, Dargusch R, Maher P, Schubert D. The regulation of glucose metabolism by HIF-1 mediates a neuroprotective response to amyloid beta peptide. Neuron. 2003;39(1):43\u201356.","journal-title":"Neuron"},{"issue":"8","key":"238_CR33","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1016\/j.bbadis.2013.09.010","volume":"1842","author":"RH Swerdlow","year":"2014","unstructured":"Swerdlow RH, Burns JM, Khan SM. The Alzheimer\u2019s disease mitochondrial cascade hypothesis: progress and perspectives. Biochim Biophys Acta. 2014;1842(8):1219\u201331.","journal-title":"Biochim Biophys Acta"},{"issue":"4","key":"238_CR34","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1007\/s11064-009-9922-y","volume":"34","author":"T Takeda","year":"2009","unstructured":"Takeda T. Senescence-accelerated mouse (SAM) with special references to neurodegeneration models, SAMP8 and SAMP10 mice. Neurochem Res. 2009;34(4):639\u201359.","journal-title":"Neurochem Res"},{"unstructured":"Warnes, G.R., et al. gplots: various SR programming tools for plotting data. (Version 3.0.1) https:\/\/CRAN.R-project.org\/package=gplots 2016 [cited 2018 Nov 20]; Available from: Please use the canonical form https:\/\/CRAN.R-project.org\/package=gplots to link to this page.","key":"238_CR35"},{"key":"238_CR36","doi-asserted-by":"publisher","first-page":"15145","DOI":"10.1038\/srep15145","volume":"5","author":"J Yang","year":"2015","unstructured":"Yang J, et al. Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases. Sci Rep. 2015;5:15145.","journal-title":"Sci Rep"},{"key":"238_CR37","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1113\/JP270541","volume":"594","author":"F Yin","year":"2016","unstructured":"Yin F, Sancheti H, Liu Z, Cadenas E. Mitochondrial function in ageing: coordination with signalling and transcriptional pathways. J Physiol. 2016;594:2025\u201342.","journal-title":"J Physiol"},{"key":"238_CR38","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.ebiom.2018.09.015","volume":"36","author":"MJ Yousefzadeh","year":"2018","unstructured":"Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18\u201328.","journal-title":"EBioMedicine"}],"container-title":["GeroScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-020-00238-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11357-020-00238-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-020-00238-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T23:27:55Z","timestamp":1626996475000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11357-020-00238-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,23]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["238"],"URL":"https:\/\/doi.org\/10.1007\/s11357-020-00238-5","relation":{},"ISSN":["2509-2715","2509-2723"],"issn-type":[{"type":"print","value":"2509-2715"},{"type":"electronic","value":"2509-2723"}],"subject":[],"published":{"date-parts":[[2020,7,23]]},"assertion":[{"value":"5 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The Salk Institute holds the patent for CAD031.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}