{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:28:51Z","timestamp":1788445731554,"version":"build-2803163510"},"reference-count":130,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>Cellular senescence has emerged as a key contributor to brain aging and neurodegenerative diseases, which are increasing in prevalence as life expectancy rises. Senescent cells accumulate in multiple brain cell populations and secrete the senescence-associated secretory phenotype (SASP), promoting chronic neuroinflammation, mitochondrial dysfunction, blood\u2013brain barrier disruption, and progressive neuronal damage. This review examines the role of cellular senescence in brain aging and neurodegenerative diseases and discusses senotherapeutic strategies aimed at either eliminating senescent cells (senolytics) or modulating the SASP (senomorphics). Particular emphasis is placed on nutritional senotherapeutics, naturally occurring bioactive compounds derived from dietary sources that target molecular pathways involved in cellular senescence. Senomorphic compounds such as sulforaphane, curcumin, and resveratrol primarily attenuate oxidative stress and inflammatory signaling, whereas senolytic agents including quercetin and fisetin selectively promote the elimination of senescent cells by disrupting pro-survival pathways. Current evidence from experimental models and emerging clinical studies suggests that nutritional senotherapeutics represent promising complementary strategies for modulating cellular senescence and promoting brain health. However, their clinical translation remains constrained by limited human evidence, low bioavailability, and unresolved challenges related to optimal dosing and blood\u2013brain barrier penetration, highlighting the need for well-designed clinical trials before their therapeutic potential can be fully established.<\/jats:p>","DOI":"10.3389\/fnut.2026.1824908","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:27:56Z","timestamp":1785756476000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting cellular senescence through nutritional senotherapeutics in brain aging and neurodegenerative diseases"],"prefix":"10.3389","volume":"13","author":[{"given":"Ver\u00f3nica","family":"Salas-Venegas","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n en Medicina Experimental, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, CDMX","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma E.","family":"L\u00f3pez-Diazguerrero","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias de la Salud, Divisi\u00f3n de Ciencias Biol\u00f3gicas y de la Salud (DCBS), Universidad Aut\u00f3noma Metropolitana Iztapalapa, CDMX","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo J.","family":"Ram\u00edrez-Carreto","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n en Medicina Experimental, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, CDMX","place":["Mexico City, Mexico"]},{"name":"Programa de Doctorado en Ciencias Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, CDMX","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Konigsberg","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias de la Salud, Divisi\u00f3n de Ciencias Biol\u00f3gicas y de la Salud (DCBS), Universidad Aut\u00f3noma Metropolitana Iztapalapa, CDMX","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anah\u00ed","family":"Chavarr\u00eda","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n en Medicina Experimental, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, CDMX","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2451","DOI":"10.18502\/ijph.v50i12.7927","article-title":"The impact of population ageing: a review","volume":"50","author":"Ismail","year":"2021","journal-title":"Int J Public Health"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1281581","DOI":"10.3389\/fnagi.2023.1281581","article-title":"Cellular senescence in brain aging and cognitive decline","volume":"15","author":"Shafqat","year":"2023","journal-title":"Front Aging Neurosci"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1007\/s00204-024-03768-5","article-title":"The role of cellular senescence in neurodegenerative diseases","volume":"98","author":"Wang","year":"2024","journal-title":"Arch Toxicol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e12840","DOI":"10.1111\/acel.12840","article-title":"Tau protein aggregation is associated with cellular senescence in the brain","volume":"17","author":"Musi","year":"2018","journal-title":"Aging Cell"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"111675","DOI":"10.1016\/j.mad.2022.111675","article-title":"Cellular senescence in the aging brain: a promising target for neurodegenerative diseases","volume":"204","author":"Sahu","year":"2022","journal-title":"Mech Ageing Dev"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"111327","DOI":"10.1016\/j.biopha.2021.111327","article-title":"Evidence and perspectives of cell senescence in neurodegenerative diseases","volume":"137","author":"Si","year":"2021","journal-title":"Biomed Pharmacother"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1007\/s10068-022-01114-y","article-title":"Nutritional components as mitigators of cellular senescence in organismal aging: a comprehensive review","volume":"31","author":"Diwan","year":"2022","journal-title":"Food Sci Biotechnol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"958563","DOI":"10.3389\/fnut.2022.958563","article-title":"Nutritional senolytics and senomorphics: implications to immune cells metabolism and aging \u2013 from theory to practice","volume":"9","author":"Lu\u00eds","year":"2022","journal-title":"Front Nutr"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: an expanding universe","volume":"186","author":"L\u00f3pez-Ot\u00edn","year":"2023","journal-title":"Cell"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"646924","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":"ref11","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1038\/nrm2233","article-title":"Cellular senescence: when bad things happen to good cells","volume":"8","author":"Campisi","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"102141","DOI":"10.1016\/j.arr.2023.102141","article-title":"Cellular senescence in brain aging and neurodegeneration","volume":"93","author":"Melo Dos Santos","year":"2024","journal-title":"Ageing Res Rev"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"101251","DOI":"10.1016\/j.arr.2020.101251","article-title":"Senescent cells as promising targets to tackle age-related diseases","volume":"66","author":"Pra\u0161nikar","year":"2021","journal-title":"Ageing Res Rev"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1124\/pharmrev.122.000622","article-title":"Cellular senescence: from mechanisms to current biomarkers and Senotherapies","volume":"75","author":"Lucas","year":"2023","journal-title":"Pharmacol Rev"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"104717","DOI":"10.1016\/j.ebiom.2023.104717","article-title":"Cellular senescence in asthma: from pathogenesis to therapeutic challenges","volume":"94","author":"Wan","year":"2023","journal-title":"EBioMedicine"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/B978-0-12-822514-1.00012-2","volume-title":"Cellular Senescence in Disease","author":"Zhang","year":"2022"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.14336\/AD.2023.0214","article-title":"Neuronal senescence in the aged brain","volume":"14","author":"Chou","year":"2023","journal-title":"Aging Dis"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1146\/annurev-pathol-121808-102144","article-title":"The senescence-associated secretory phenotype: the dark side of tumor suppression","volume":"5","author":"Copp\u00e9","year":"2010","journal-title":"Annu Rev Pathol Mech Dis"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1016\/j.devcel.2014.11.012","article-title":"An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA","volume":"31","author":"Demaria","year":"2014","journal-title":"Dev Cell"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1111\/j.1474-9726.2012.00870.x","article-title":"Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response","volume":"11","author":"Jurk","year":"2012","journal-title":"Aging Cell"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e12937","DOI":"10.1111\/acel.12937","article-title":"Astrocyte senescence: evidence and significance","volume":"18","author":"Cohen","year":"2019","journal-title":"Aging Cell"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1002\/nep3.56","article-title":"Microglial senescence in neurodegeneration: insights, implications, and therapeutic opportunities","volume":"2","author":"Olajide","year":"2024","journal-title":"Neuroprotection"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/s41593-019-0372-9","article-title":"Senolytic therapy alleviates a\u03b2-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer\u2019s disease model","volume":"22","author":"Zhang","year":"2019","journal-title":"Nat Neurosci"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1172\/JCI95145","article-title":"Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives","volume":"128","author":"Baker","year":"2018","journal-title":"J Clin Invest"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"645593","DOI":"10.3389\/fcell.2021.645593","article-title":"Mechanisms of cellular senescence: cell cycle arrest and senescence associated secretory phenotype","volume":"9","author":"Kumari","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1002\/alz.13490","article-title":"Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer\u2019s disease: evidence from clinical and preclinical studies","volume":"20","author":"Gaikwad","year":"2024","journal-title":"Alzheimers Dement"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3389\/fnagi.2020.00148","article-title":"Astrocyte senescence and Alzheimer\u2019s disease: a review","volume":"12","author":"Han","year":"2020","journal-title":"Front Aging Neurosci"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"4168","DOI":"10.3390\/ijms23084168","article-title":"Cellular senescence: molecular targets, biomarkers, and Senolytic drugs","volume":"23","author":"Kudlova","year":"2022","journal-title":"IJMS"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/s41581-022-00601-z","article-title":"Cellular senescence: the good, the bad and the unknown","volume":"18","author":"Huang","year":"2022","journal-title":"Nat Rev Nephrol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"glad265","DOI":"10.1093\/gerona\/glad265","article-title":"Proteomic analysis of the senescence-associated secretory phenotype: GDF-15, IGFBP-2, and cystatin-C are associated with multiple aging traits","volume":"79","author":"Evans","year":"2024","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e14006","DOI":"10.1111\/acel.14006","article-title":"Biomarkers of cellular senescence and risk of death in humans","volume":"22","author":"St Sauver","year":"2023","journal-title":"Aging Cell"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.3390\/cells13211788","article-title":"Molecular and cellular effects of microplastics and Nanoplastics: focus on inflammation and senescence","volume":"13","author":"Mahmud","year":"2024","journal-title":"Cells"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3389\/fncel.2020.00016","article-title":"Cellular senescence in neurodegenerative diseases","volume":"14","author":"Mart\u00ednez-Cu\u00e9","year":"2020","journal-title":"Front Cell Neurosci"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1111\/febs.16350","article-title":"Targeting cellular senescence with senotherapeutics: senolytics and senomorphics","volume":"290","author":"Zhang","year":"2023","journal-title":"FEBS J"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s40035-024-00447-4","article-title":"Cellular senescence in Alzheimer\u2019s disease: from physiology to pathology","volume":"13","author":"Zhu","year":"2024","journal-title":"Transl Neurodegener"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"111589","DOI":"10.1016\/j.mad.2021.111589","article-title":"A geroscience motivated approach to treat Alzheimer\u2019s disease: Senolytics move to clinical trials","volume":"200","author":"Gonzales","year":"2021","journal-title":"Mech Ageing Dev"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"824191","DOI":"10.3389\/fnins.2022.824191","article-title":"Neuroglial senescence, \u03b1-Synucleinopathy, and the therapeutic potential of Senolytics in Parkinson\u2019s disease","volume":"16","author":"Miller","year":"2022","journal-title":"Front Neurosci"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.exger.2014.09.018","article-title":"Cellular senescence and the aging brain","volume":"68","author":"Chinta","year":"2015","journal-title":"Exp Gerontol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1177\/1877718X251316552","article-title":"Aging, cellular senescence and Parkinson\u2019s disease","volume":"15","author":"Ma","year":"2025","journal-title":"J Parkinsons Dis"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.tins.2024.09.006","article-title":"Defining and characterizing neuronal senescence, \u2018neurescence\u2019, as GX arrested cells","volume":"47","author":"Hudson","year":"2024","journal-title":"Trends Neurosci"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.3390\/biomedicines13061400","article-title":"Role of cellular senescence in Parkinson\u2019s disease: potential for disease-modification through Senotherapy","volume":"13","author":"Rademacher","year":"2025","journal-title":"Biomedicine"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1599492","DOI":"10.3389\/fnins.2025.1599492","article-title":"The emerging role of cellular senescence in amyotrophic lateral sclerosis","volume":"19","author":"Tan","year":"2025","journal-title":"Front Neurosci"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"42","DOI":"10.3389\/fnagi.2019.00042","article-title":"Emergence of microglia bearing senescence markers during paralysis progression in a rat model of inherited ALS","volume":"11","author":"Trias","year":"2019","journal-title":"Front Aging Neurosci"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1007\/s00415-009-5069-7","article-title":"Amyotrophic lateral sclerosis, frontotemporal dementia and beyond: the TDP-43 diseases","volume":"256","author":"Geser","year":"2009","journal-title":"J Neurol"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"12335","DOI":"10.3390\/ijms252212335","article-title":"The mechanistic link between tau-driven Proteotoxic stress and cellular senescence in Alzheimer\u2019s disease","volume":"25","author":"Tangavelou","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"e13226","DOI":"10.1111\/acel.13226","article-title":"FOXO3 targets are reprogrammed as Huntington\u2019s disease neural cells and striatal neurons face senescence with p16INK4a increase","volume":"19","author":"Voisin","year":"2020","journal-title":"Aging Cell"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"115","DOI":"10.3233\/JHD-200395","article-title":"Biological aging and the cellular pathogenesis of Huntington\u2019s disease","volume":"9","author":"Machiela","year":"2020","journal-title":"J Huntingtons Dis"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"5511","DOI":"10.1007\/s11357-025-01621-w","article-title":"Cerebromicrovascular senescence in vascular cognitive impairment: does accelerated microvascular aging accompany atherosclerosis?","volume":"47","author":"Ungvari","year":"2025","journal-title":"Geroscience"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1161\/STROKEAHA.115.010835","article-title":"Vascular cell senescence contributes to blood-brain barrier breakdown","volume":"47","author":"Yamazaki","year":"2016","journal-title":"Stroke"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"111585","DOI":"10.1016\/j.mad.2021.111585","article-title":"A guide to senolytic intervention in neurodegenerative disease","volume":"200","author":"Lee","year":"2021","journal-title":"Mech Ageing Dev"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.semcancer.2019.09.020","article-title":"Systems biology based drug repositioning for development of cancer therapy","volume":"68","author":"Turanli","year":"2021","journal-title":"Semin Cancer Biol"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"860","DOI":"10.3390\/biom15060860","article-title":"Targeting senescence: a review of Senolytics and Senomorphics in anti-aging interventions","volume":"15","author":"Saliev","year":"2025","journal-title":"Biomolecules"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.freeradbiomed.2021.05.003","article-title":"Senolytics and senomorphics: natural and synthetic therapeutics in the treatment of aging and chronic diseases","volume":"171","author":"Lagoumtzi","year":"2021","journal-title":"Free Radic Biol Med"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"151240","DOI":"10.1016\/j.ejcb.2022.151240","article-title":"Amino acids control blood glucose levels through mTOR signaling","volume":"101","author":"Fan","year":"2022","journal-title":"Eur J Cell Biol"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"781","DOI":"10.3390\/cells13090781","article-title":"Nuclear mTOR signaling orchestrates transcriptional programs underlying cellular growth and metabolism","volume":"13","author":"Zhao","year":"2024","journal-title":"Cells"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1771707","DOI":"10.3389\/fgene.2026.1771707","article-title":"Molecular mechanisms underlying the lifespan and healthspan benefits of dietary restriction across species","volume":"17","author":"Fan","year":"2026","journal-title":"Front Genet"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"116811","DOI":"10.1016\/j.celrep.2025.116811","article-title":"PDX1 phosphorylation at S61 by mTORC1 links nutrient signaling to \u03b2 cell function and metabolic disease","volume":"45","author":"Fan","year":"2026","journal-title":"Cell Rep"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"102238","DOI":"10.1016\/j.arr.2024.102238","article-title":"Therapeutic effect of dietary ingredients on cellular senescence in animals and humans: a systematic review","volume":"95","author":"Guan","year":"2024","journal-title":"Ageing Res Rev"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"148905","DOI":"10.1016\/j.brainres.2024.148905","article-title":"Exploring the potential of quercetin in Alzheimer\u2019s disease: pharmacodynamics, pharmacokinetics, and Nanodelivery systems","volume":"1834","author":"Kaur","year":"2024","journal-title":"Brain Res"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1593264","DOI":"10.3389\/fphar.2025.1593264","article-title":"Neuroprotective potential of quercetin in Alzheimer\u2019s disease: targeting oxidative stress, mitochondrial dysfunction, and amyloid-\u03b2 aggregation","volume":"16","author":"Adnan","year":"2025","journal-title":"Front Pharmacol"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/bcpt.14011","article-title":"Effects of quercetin in preclinical models of Parkinson\u2019s disease: a systematic review","volume":"135","author":"De Oliveira Vian","year":"2024","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1007\/s11064-020-03058-3","article-title":"Promising polyphenols in Parkinson\u2019s disease therapeutics","volume":"45","author":"Singh","year":"2020","journal-title":"Neurochem Res"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s11658-022-00355-3","article-title":"Quercetin as a JAK\u2013STAT inhibitor: a potential role in solid tumors and neurodegenerative diseases","volume":"27","author":"Zalpoor","year":"2022","journal-title":"Cell Mol Biol Lett"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"633","DOI":"10.14283\/jpad.2023.104","article-title":"Translating the biology of aging into new therapeutics for Alzheimer\u2019s disease: Senolytics","volume":"10","author":"Riessland","year":"2023","journal-title":"J Prev Alzheimers Dis"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"955","DOI":"10.18632\/aging.101202","article-title":"New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463","volume":"9","author":"Zhu","year":"2017","journal-title":"Aging"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.ebiom.2018.09.015","article-title":"Fisetin is a senotherapeutic that extends health and lifespan","volume":"36","author":"Yousefzadeh","year":"2018","journal-title":"EBioMedicine"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1111\/acel.12185","article-title":"Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in a lzheimer\u2019s disease transgenic mice","volume":"13","author":"Currais","year":"2014","journal-title":"Aging Cell"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.jphs.2017.12.008","article-title":"Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo","volume":"136","author":"He","year":"2018","journal-title":"J Pharmacol Sci"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"100319","DOI":"10.1016\/j.lddd.2026.100319","article-title":"Targeting PI3K\/Akt\/mTOR with fisetin mechanistic and therapeutics insights for Parkinson\u2019s disease","volume":"22","author":"Barik","year":"2026","journal-title":"Lett Drug Des Discov"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.2174\/1568026616666160204121725","article-title":"Neuroprotective effects of Fisetin in Alzheimer\u2019s and Parkinson\u2019s diseases: from chemistry to medicine","volume":"16","author":"Nabavi","year":"2016","journal-title":"Curr Top Med Chem"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"738","DOI":"10.3390\/molecules27030738","article-title":"Fisetin as a Senotherapeutic agent: biopharmaceutical properties and crosstalk between cell senescence and neuroprotection","volume":"27","author":"Elsallabi","year":"2022","journal-title":"Molecules"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"1015835","DOI":"10.3389\/fphar.2022.1015835","article-title":"The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: focus on the role of oxidative stress","volume":"13","author":"Hassan","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"8637","DOI":"10.3390\/ijms21228637","article-title":"Efficacy of Sulforaphane in neurodegenerative diseases","volume":"21","author":"Schepici","year":"2020","journal-title":"IJMS"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.3233\/JAD-171110","article-title":"Sulforaphane inhibits the generation of amyloid- \u03b2 oligomer and promotes spatial learning and memory in Alzheimer\u2019s disease (PS1V97L) transgenic mice","volume":"62","author":"Hou","year":"2018","journal-title":"J Alzheimer's Dis"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"1800240","DOI":"10.1002\/mnfr.201800240","article-title":"Sulforaphane upregulates the heat shock protein co-chaperone CHIP and clears amyloid-\u03b2 and tau in a mouse model of Alzheimer\u2019s disease","volume":"62","author":"Lee","year":"2018","journal-title":"Mol Nutr Food Res"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1007\/s11357-019-00061-7","article-title":"Sulforaphane - role in aging and neurodegeneration","volume":"41","author":"Sant\u00edn-M\u00e1rquez","year":"2019","journal-title":"GeroScience"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1002\/npr2.12060","article-title":"Dietary intake of glucoraphanin prevents the reduction of dopamine transporter in the mouse striatum after repeated administration of MPTP","volume":"39","author":"Pu","year":"2019","journal-title":"Neuropsychopharmacol Rep"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"7857186","DOI":"10.1155\/2016\/7857186","article-title":"Sulforaphane and other nutrigenomic Nrf2 activators: can the clinician\u2019s expectation be matched by the reality?","volume":"2016","author":"Houghton","year":"2016","journal-title":"Oxidative Med Cell Longev"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"1558025","DOI":"10.3389\/fnut.2025.1558025","article-title":"Editorial: Sulforaphane and isothiocyanates in health","volume":"12","author":"Fahey","year":"2025","journal-title":"Front Nutr"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1002\/biof.1063","article-title":"Curcumin and neurodegenerative diseases","volume":"39","author":"Monroy","year":"2013","journal-title":"Biofactors"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"e70369","DOI":"10.1002\/jbt.70369","article-title":"Neuroprotective potential of curcumin in neurodegenerative diseases: clinical insights into cellular and molecular signaling pathways","volume":"39","author":"Islam","year":"2025","journal-title":"J Biochem Mol Toxicol"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"111119","DOI":"10.1016\/j.biopha.2020.111119","article-title":"The role of curcumin in aging and senescence: molecular mechanisms","volume":"134","author":"Zia","year":"2021","journal-title":"Biomed Pharmacother"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"441","DOI":"10.12047\/j.cjap.5548.2017.106","article-title":"Effects of curcumin on the recovery of hind limb function after spinal cord injury in rats and its mechamism","volume":"33","author":"Hao","year":"2017","journal-title":"Zhongguo Ying Yong Sheng Li Xue Za Zhi"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1177\/1545968310397706","article-title":"Brain and spinal cord interaction: a dietary curcumin derivative counteracts locomotor and cognitive deficits after brain trauma","volume":"25","author":"Wu","year":"2011","journal-title":"Neurorehabil Neural Repair"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.3390\/foods13111774","article-title":"Neuroprotective effects of curcumin in neurodegenerative diseases","volume":"13","author":"Genchi","year":"2024","journal-title":"Foods"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"1625821","DOI":"10.3389\/fphar.2025.1625821","article-title":"Pharmacological effects, molecular mechanisms and strategies to improve bioavailability of curcumin in the treatment of neurodegenerative diseases","volume":"16","author":"Wang","year":"2025","journal-title":"Front Pharmacol"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"1271941","DOI":"10.3389\/fneur.2023.1271941","article-title":"Senolytic and senomorphic secondary metabolites as therapeutic agents in Drosophila melanogaster models of Parkinson\u2019s disease","volume":"14","author":"Miller","year":"2023","journal-title":"Front Neurol"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"147","DOI":"10.5152\/pcp.2023.23633","article-title":"Resveratrol in neurodegeneration, in neurodegenerative diseases, and in the redox biology of the mitochondria","volume":"33","author":"Danisman","year":"2023","journal-title":"Psychiatry Clin Psychopharmacol"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1111\/j.1749-6632.2010.05857.x","article-title":"Resveratrol modulates astroglial functions: neuroprotective hypothesis","volume":"1215","author":"Quincozes-Santos","year":"2011","journal-title":"Ann N Y Acad Sci"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/s41698-017-0038-6","article-title":"The therapeutic potential of resveratrol: a review of clinical trials","volume":"1","author":"Berman","year":"2017","journal-title":"NPJ Precis Oncol"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1212\/WNL.0000000000002035","article-title":"A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease","volume":"85","author":"Turner","year":"2015","journal-title":"Neurology"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12974-016-0779-0","article-title":"Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer\u2019s disease","volume":"14","author":"Moussa","year":"2017","journal-title":"J Neuroinflammation"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"84","DOI":"10.4103\/0973-7847.194044","article-title":"Overviews of biological importance of quercetin: a bioactive flavonoid","volume":"10","author":"Anand David","year":"2016","journal-title":"Phcog Rev"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"23237","DOI":"10.1038\/s41598-021-02544-0","article-title":"Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence","volume":"11","author":"Zoico","year":"2021","journal-title":"Sci Rep"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.3233\/JAD-170093","article-title":"Curcumin ameliorates Neuroinflammation, neurodegeneration, and memory deficits in p25 transgenic mouse model that bears hallmarks of Alzheimer\u2019s disease","volume":"60","author":"Sundaram","year":"2017","journal-title":"J Alzheimer's Dis"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1002\/mds.27665","article-title":"Modifiable risk factors for cognitive impairment in Parkinson\u2019s disease: a systematic review and meta-analysis of prospective cohort studies","volume":"34","author":"Guo","year":"2019","journal-title":"Mov Disord"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"101275","DOI":"10.1016\/j.smim.2019.04.003","article-title":"Senescent cell clearance by the immune system: emerging therapeutic opportunities","volume":"40","author":"Prata","year":"2018","journal-title":"Semin Immunol"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"e67","DOI":"10.1016\/S2666-7568(21)00300-7","article-title":"The costs and benefits of senotherapeutics for human health","volume":"3","author":"Raffaele","year":"2022","journal-title":"Lancet Healthy Longev"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.stem.2018.04.004","article-title":"Human adult neurogenesis: evidence and remaining questions","volume":"23","author":"Kempermann","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3389\/fncel.2020.00129","article-title":"Senescence as an amyloid Cascade: the amyloid senescence hypothesis","volume":"14","author":"Walton","year":"2020","journal-title":"Front Cell Neurosci"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1111\/febs.16649","article-title":"Senescent cells in the brain and where to find them","volume":"290","author":"Rachmian","year":"2023","journal-title":"FEBS J"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.addr.2019.11.009","article-title":"The blood-brain barrier: physiology and strategies for drug delivery","author":"Pandit","year":"2020","journal-title":"Adv Drug Deliv Rev"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1602\/neurorx.2.1.3","article-title":"The blood-brain barrier: bottleneck in brain drug development","volume":"2","author":"Pardridge","year":"2005","journal-title":"Neurotherapeutics"},{"key":"ref104","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.tins.2020.12.002","article-title":"Blood\u2013brain barrier dynamics to maintain brain homeostasis","volume":"44","author":"Segarra","year":"2021","journal-title":"Trends Neurosci"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"1600766","DOI":"10.1002\/mnfr.201600766","article-title":"Stabilized sulforaphane for clinical use: phytochemical delivery efficiency","volume":"61","author":"Fahey","year":"2017","journal-title":"Mol Nutr Food Res"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/s12276-022-00789-x","article-title":"TNF-\u03b1 promotes \u03b1-synuclein propagation through stimulation of senescence-associated lysosomal exocytosis","volume":"54","author":"Bae","year":"2022","journal-title":"Exp Mol Med"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"2824","DOI":"10.3390\/cells12242824","article-title":"Microglial senescence and activation in healthy aging and Alzheimer\u2019s disease: systematic review and neuropathological scoring","volume":"12","author":"Malvaso","year":"2023","journal-title":"Cells"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"1079626","DOI":"10.3389\/fendo.2023.1079626","article-title":"Drugs against metabolic diseases as potential senotherapeutics for aging-related respiratory diseases","volume":"14","author":"Matsubayashi","year":"2023","journal-title":"Front Endocrinol"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"766306","DOI":"10.3389\/fnagi.2021.766306","article-title":"Senescence in primary rat astrocytes induces loss of the mitochondrial membrane potential and alters mitochondrial dynamics in cortical neurons","volume":"13","author":"Morales-Rosales","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"ref110","doi-asserted-by":"publisher","first-page":"6217","DOI":"10.3390\/ijms23116217","article-title":"Blood\u2013brain barrier dysfunction and astrocyte senescence as reciprocal drivers of neuropathology in aging","volume":"23","author":"Preininger","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref111","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1038\/nn.2946","article-title":"Central nervous system pericytes in health and disease","volume":"14","author":"Winkler","year":"2011","journal-title":"Nat Neurosci"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"105040","DOI":"10.1016\/j.nbd.2020.105040","article-title":"Convergent epigenetic regulation of glial plasticity in myelin repair and brain tumorigenesis: a focus on histone modifying enzymes","volume":"144","author":"Wang","year":"2020","journal-title":"Neurobiol Dis"},{"key":"ref113","doi-asserted-by":"publisher","first-page":"NS20210008","DOI":"10.1042\/NS20210008","article-title":"Oligodendrocytes in the aging brain","volume":"5","author":"Sams","year":"2021","journal-title":"Neuronal Signaling"},{"key":"ref114","doi-asserted-by":"publisher","first-page":"1954","DOI":"10.3390\/cells11121954","article-title":"Reciprocal interactions between oligodendrocyte precursor cells and the neurovascular unit in health and disease","volume":"11","author":"Pfeiffer","year":"2022","journal-title":"Cells"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"5213","DOI":"10.1038\/s41467-021-25453-2","article-title":"Long-term treatment with senolytic drugs Dasatinib and quercetin ameliorates age-dependent intervertebral disc degeneration in mice","volume":"12","author":"Novais","year":"2021","journal-title":"Nat Commun"},{"key":"ref116","doi-asserted-by":"publisher","first-page":"354","DOI":"10.3389\/fcell.2020.00354","article-title":"The senolytic drug Navitoclax (ABT-263) causes trabecular bone loss and impaired osteoprogenitor function in aged mice","volume":"8","author":"Sharma","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"ref117","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1158\/0008-5472.CAN-10-1977","article-title":"The BH3 mimetic ABT-737 induces Cancer cell senescence","volume":"71","author":"Song","year":"2011","journal-title":"Cancer Res"},{"key":"ref118","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.canlet.2009.07.010","article-title":"Geldanamycin and its anti-cancer activities","volume":"290","author":"Fukuyo","year":"2010","journal-title":"Cancer Lett"},{"key":"ref119","doi-asserted-by":"publisher","first-page":"4731","DOI":"10.1038\/s41467-019-12888-x","article-title":"Identification and characterization of cardiac glycosides as senolytic compounds","volume":"10","author":"Triana-Mart\u00ednez","year":"2019","journal-title":"Nat Commun"},{"key":"ref120","doi-asserted-by":"publisher","first-page":"2915","DOI":"10.18632\/aging.101100","article-title":"Discovery of piperlongumine as a potential novel lead for the development of senolytic agents","volume":"8","author":"Wang","year":"2016","journal-title":"Aging"},{"key":"ref121","doi-asserted-by":"publisher","first-page":"e62635","DOI":"10.7554\/eLife.62635","article-title":"Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction","volume":"10","author":"Le Pelletier","year":"2021","journal-title":"eLife"},{"key":"ref122","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1016\/j.bbrc.2005.07.014","article-title":"Aspirin reduces endothelial cell senescence","volume":"334","author":"Bode-B\u00f6ger","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"key":"ref123","doi-asserted-by":"publisher","first-page":"771","DOI":"10.18632\/aging.101787","article-title":"The curcumin analog EF24 is a novel senolytic agent","volume":"11","author":"Li","year":"2019","journal-title":"Aging"},{"key":"ref124","doi-asserted-by":"publisher","first-page":"3925","DOI":"10.12659\/MSM.902491","article-title":"Kaempferol alleviates the interleukin-1\u03b2-induced inflammation in rat osteoarthritis chondrocytes via suppression of NF-\u03baB","volume":"23","author":"Zhuang","year":"2017","journal-title":"Med Sci Monit"},{"key":"ref125","doi-asserted-by":"publisher","first-page":"41421","DOI":"10.18632\/oncotarget.9404","article-title":"Apigenin inhibits NF-\u03baB and snail signaling, EMT and metastasis in human hepatocellular carcinoma","volume":"7","author":"Qin","year":"2106","journal-title":"Oncotarget"},{"key":"ref126","doi-asserted-by":"publisher","first-page":"111665","DOI":"10.1016\/j.mad.2022.111665","article-title":"Genistein, a tool for geroscience","volume":"204","author":"Mas- Bargues","year":"2022","journal-title":"Mech Ageing Dev"},{"key":"ref127","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1038\/s41591-018-0092-9","article-title":"Senolytics improve physical function and increase lifespan in old age","volume":"24","author":"Xu","year":"2018","journal-title":"Nat Med"},{"key":"ref128","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.ebiom.2019.08.069","article-title":"Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of Dasatinib plus quercetin in individuals with diabetic kidney disease","volume":"47","author":"Hickson","year":"2019","journal-title":"EBioMedicine"},{"key":"ref129","doi-asserted-by":"publisher","first-page":"104481","DOI":"10.1016\/j.ebiom.2023.104481","article-title":"Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis: results of a phase I, single-blind, single-center, randomized, placebo-controlled pilot trial on feasibility and tolerability","volume":"90","author":"Nambiar","year":"2023","journal-title":"EBioMedicine"},{"key":"ref130","doi-asserted-by":"publisher","first-page":"105790","DOI":"10.1016\/j.neuint.2024.105790","article-title":"Curcumin as a potential therapeutic agent for treating neurodegenerative diseases","volume":"178","author":"Perales-Salinas","year":"2024","journal-title":"Neurochem Int"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1824908\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:27:58Z","timestamp":1785756478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1824908\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":130,"alternative-id":["10.3389\/fnut.2026.1824908"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1824908","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]},"article-number":"1824908"}}