{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:05:16Z","timestamp":1780549516712,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100024065","name":"OM Pharma","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100024065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Mitochondrial dysfunction is a central feature of aging, driving bioenergetic decline, increased oxidative stress, and increased vulnerability to neurodegenerative diseases. Human induced pluripotent stem cells (iPSCs) and iPSC-derived neurons provide powerful models to study these processes. Ginkgo biloba extract GBE LI1370 (GBE) has demonstrated antioxidant and mitochondria-protective properties in preclinical models, including improvements in mitochondrial membrane potential, reduction in reactive oxygen species, and enhanced neuronal survival. However, its effects on mitochondrial function in human iPSCs and their differentiated derivatives in the context of aging have not yet been investigated. This study evaluated the mitochondrial protective effects of GBE (100 \u00b5g\/mL) in an established iPSC-based model of aging and in neurons and astrocytes derived from aged iPSCs. Mitochondrial parameters, including ATP production, mitochondrial membrane potential (MMP), mitochondrial reactive oxygen species (mtROS), superoxide levels, and mitochondrial respiration, were assessed. Aged iPSCs exhibited reduced ATP production and MMP, together with increased mtROS and superoxide levels compared to young controls. Astrocytes derived from aged iPSCs also displayed mitochondrial dysfunction. Treatment with GBE for 24 h increased ATP production and MMP, reduced oxidative stress, and improved mitochondrial respiration in both young and aged iPSCs, as well as in aged iPSC-derived neurons and astrocytes. These preliminary donor-based findings support further investigation of GBE-associated mitochondrial responses in human donor-derived cellular models of aging and warrant validation in larger donor cohorts.<\/jats:p>","DOI":"10.3390\/antiox15060689","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:33:14Z","timestamp":1780479194000},"page":"689","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ginkgo Biloba Extract Ameliorates Age-Related Mitochondrial Deficits in Human iPSCs and Their Derived Neurons and Astrocytes"],"prefix":"10.3390","volume":"15","author":[{"given":"Imane","family":"Lejri","sequence":"first","affiliation":[{"name":"Neurobiology Lab for Brain Aging and Mental Health, University Psychiatric Clinics UPKl, 4002 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3323-1756","authenticated-orcid":false,"given":"Amandine","family":"Grimm","sequence":"additional","affiliation":[{"name":"Neurobiology Lab for Brain Aging and Mental Health, University Psychiatric Clinics UPKl, 4002 Basel, Switzerland"},{"name":"Department of Biomedicine, University of Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-3669","authenticated-orcid":false,"given":"Anne","family":"Eckert","sequence":"additional","affiliation":[{"name":"Neurobiology Lab for Brain Aging and Mental Health, University Psychiatric Clinics UPKl, 4002 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/nature05292","article-title":"Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases","volume":"443","author":"Lin","year":"2006","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1172\/JCI64125","article-title":"The role of mitochondria in aging","volume":"123","author":"Bratic","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1172\/JCI120842","article-title":"The role of mitochondria in aging","volume":"128","author":"Jang","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_5","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":"ref_6","doi-asserted-by":"crossref","unstructured":"Barbalho, S.M., Direito, R., Laurindo, L.F., Marton, L.T., Guiguer, E.L., Goulart, R.A., Tofano, R.J., Carvalho, A.C.A., Flato, U.A.P., and Capelluppi Tofano, V.A. (2022). Ginkgo biloba in the Aging Process: A Narrative Review. Antioxidants, 11.","DOI":"10.3390\/antiox11030525"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s10522-025-10273-4","article-title":"Mitochondrial dysfunction and aging: Multidimensional mechanisms and therapeutic strategies","volume":"26","author":"Wei","year":"2025","journal-title":"Biogerontology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/s42003-025-08152-2","article-title":"Tracing mitochondrial marks of neuronal aging in iPSCs-derived neurons and directly converted neurons","volume":"8","author":"Varghese","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lejri, I., Cader, Z., Grimm, A., and Eckert, A. (2024). Human iPSCs from Aged Donors Retain Their Mitochondrial Aging Signature. Int. J. Mol. Sci., 25.","DOI":"10.1101\/2024.04.16.589733"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1007\/s00018-003-3080-1","article-title":"Neuroprotective effects of Ginkgo biloba extract","volume":"60","author":"Ahlemeyer","year":"2003","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s00253-003-1527-9","article-title":"Studies on molecular mechanisms of Ginkgo biloba extract","volume":"64","author":"Smith","year":"2004","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lejri, I., Grimm, A., and Eckert, A. (2019). Ginkgo biloba extract increases neurite outgrowth and activates the Akt\/mTOR pathway. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0225761"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lejri, I., Vukalovi\u0107, I., Grimm, A., and Eckert, A. (2025). Proanthocyanidins from Ginkgo extract EGb 761\u00ae improve bioenergetics and stimulate neurite outgrowth in vitro. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1495997"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3390\/ijms11010107","article-title":"Ginkgo biloba extract in Alzheimer\u2019s disease: From action mechanisms to medical practice","volume":"11","author":"Shi","year":"2010","journal-title":"Int. J. Mol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1196\/annals.1352.023","article-title":"Stabilization of mitochondrial membrane potential and improvement of neuronal energy metabolism by Ginkgo biloba extract EGb 761","volume":"1056","author":"Eckert","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Rhein, V., Giese, M., Baysang, G., Meier, F., Rao, S., Schulz, K.L., Hamburger, M., and Eckert, A. (2010). Ginkgo biloba extract ameliorates oxidative phosphorylation performance and rescues abeta-induced failure. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012359"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.stem.2013.11.006","article-title":"Human iPSC-based modeling of late-onset disease via progerin-induced aging","volume":"13","author":"Miller","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.stem.2015.09.001","article-title":"Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects","volume":"17","author":"Mertens","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tang, Y., Liu, M.L., Zang, T., and Zhang, C.L. (2017). Direct Reprogramming Rather than iPSC-Based Reprogramming Maintains Aging Hallmarks in Human Motor Neurons. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00359"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1016\/j.stem.2021.04.004","article-title":"Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer\u2019s patients","volume":"28","author":"Mertens","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Szabo, L., Lejri, I., Grimm, A., and Eckert, A. (2024). Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived Neurons. Antioxidants, 13.","DOI":"10.3390\/antiox13121482"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nrn.2018.19","article-title":"Lactate in the brain: From metabolic end-product to signalling molecule","volume":"19","author":"Magistretti","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"167470","DOI":"10.1016\/j.bbadis.2024.167470","article-title":"Accumulation of damaged mitochondria in aging astrocytes due to mitophagy dysfunction: Implications for susceptibility to mitochondrial stress","volume":"1870","author":"Diniz","year":"2024","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Labarta-Bajo, L., Thanawalla, A.R., Gutierrez, I.L., Lei Soe, S.M., Chick, B.Y., Andritsogianni, I., Metanat, S., Hargreaves, D.C., Kaech, S.M., and Azim, E. (2025). The antiviral Interferon pathway drives astrocyte aging and motor decline. bioRxiv.","DOI":"10.1101\/2025.11.12.688147"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.cmet.2011.08.016","article-title":"Brain energy metabolism: Focus on astrocyte-neuron metabolic cooperation","volume":"14","author":"Allaman","year":"2011","journal-title":"Cell Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1016\/j.cmet.2021.07.006","article-title":"Astrocyte-neuron metabolic cooperation shapes brain activity","volume":"33","author":"Bonvento","year":"2021","journal-title":"Cell Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100902","DOI":"10.1016\/j.xpro.2021.100902","article-title":"Differentiation of functional astrocytes from human-induced pluripotent stem cells in chemically defined media","volume":"2","author":"Perriot","year":"2021","journal-title":"STAR Protoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"874","DOI":"10.2144\/00294rr04","article-title":"Automated image analysis of live\/dead staining of the fungus Aureobasidium pullulans on microscope slides and leaf surfaces","volume":"29","author":"Nelson","year":"2000","journal-title":"Biotechniques"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.molcel.2016.01.028","article-title":"The Mitochondrial Basis of Aging","volume":"61","author":"Sun","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Yu, P., Liu, B., Dong, C., and Chang, Y. (2025). Induced Pluripotent Stem Cells-Based Regenerative Therapies in Treating Human Aging-Related Functional Decline and Diseases. Cells, 14.","DOI":"10.3390\/cells14080619"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41583-022-00641-1","article-title":"Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders","volume":"24","author":"Brandebura","year":"2023","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.3390\/cimb46030130","article-title":"Mitochondrial Dysfunction: A Key Player in Brain Aging and Diseases","volume":"46","author":"Bartman","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S285","DOI":"10.3233\/JAD-231372","article-title":"Pharmacodynamic and Clinical Effects of Ginkgo biloba Extract EGb 761 and Its Phytochemical Components in Alzheimer\u2019s Disease","volume":"101","author":"Tartari","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1055\/s-0030-1250286","article-title":"Plasma and brain levels of terpene trilactones in rats after an oral single dose of standardized Ginkgo biloba extract EGb 761\u00ae","volume":"77","author":"Ude","year":"2011","journal-title":"Planta Medica"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"393","DOI":"10.2174\/156720511795745401","article-title":"Mitochondria as a therapeutic target for aging and neurodegenerative diseases","volume":"8","author":"Reddy","year":"2011","journal-title":"Curr. Alzheimer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"192503","DOI":"10.1155\/2012\/192503","article-title":"Is There a Link between Mitochondrial Reserve Respiratory Capacity and Aging?","volume":"2012","author":"Desler","year":"2012","journal-title":"J. Aging Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/acel.12287","article-title":"Mitochondrial effectors of cellular senescence: Beyond the free radical theory of aging","volume":"14","author":"Ziegler","year":"2015","journal-title":"Aging Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12115","DOI":"10.1007\/s00210-025-03972-9","article-title":"Ginkgo biloba L. leaf extract (EGb 761) alleviates reserpine-induced depression-like symptoms in aged rats by enhancing serotonin\/norepinephrine levels and reducing oxidative\/nitrosative stress","volume":"398","author":"Ali","year":"2025","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1007\/s11010-023-04878-x","article-title":"NRF2 signaling pathway and telomere length in aging and age-related diseases","volume":"479","author":"Medoro","year":"2024","journal-title":"Mol. Cell. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1142\/S0192415X24500277","article-title":"Ginkgo biloba and Its Chemical Components in the Management of Alzheimer\u2019s Disease","volume":"52","author":"Peng","year":"2024","journal-title":"Am. J. Chin. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s007020170016","article-title":"Age-related increase of oxidative stress-induced apoptosis in mice prevention by Ginkgo biloba extract (EGb761)","volume":"108","author":"Schindowski","year":"2001","journal-title":"J. Neural Transm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"812","DOI":"10.14336\/AD.2017.0615","article-title":"Advances in the Studies of Ginkgo biloba Leaves Extract on Aging-Related Diseases","volume":"8","author":"Zuo","year":"2017","journal-title":"Aging Dis."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/6\/689\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:26:07Z","timestamp":1780547167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/6\/689"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":42,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["antiox15060689"],"URL":"https:\/\/doi.org\/10.3390\/antiox15060689","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]}}}