{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:55:33Z","timestamp":1790574933585,"version":"4.1.0"},"reference-count":86,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cellular senescence is increasingly recognized as a fundamental driver of aging and age\u2010related diseases. Studies in peripheral tissues have revealed that senescence is not a uniform cellular state, but a highly heterogeneous phenotype shaped by distinct combinations of DNA damage, mitochondrial dysfunction, chromatin remodeling, impaired proteostasis, and diverse senescence\u2010associated secretory phenotype. This heterogeneity critically influences both the identification and therapeutic targeting of senescent cells. As senescent cells accumulate with age, they contribute to chronic low\u2010grade inflammation and tissue dysfunction, while their selective elimination can improve health span, establishing senescence as both a pathogenic mechanism and a therapeutic target in systemic aging. Emerging evidence now suggests that post\u2010mitotic neurons and other neural cell types can acquire senescence\u2010like states during aging and neurodegeneration. However, the direct application of canonical peripheral senescence markers to the nervous system remains conceptually and experimentally problematic, raising the risk of inconsistent or misleading interpretations across models and studies. In this review, we integrate insights from peripheral senescence biology to examine how cell type, inducing stressor, and experimental context shape senescence\u2010associated phenotypes across neural systems, including in\u00a0vitro models, physiologically aged brains, and models of Alzheimer's and Parkinson's disease. By critically evaluating where canonical senescence hallmarks translate and where they fail to translate to post\u2010mitotic neurons, we propose that a refined, neuron\u2010centered framework is essential for moving the field beyond descriptive observations and for rigorously testing the causal contribution of senescent neural cells to neurodegeneration.<\/jats:p>","DOI":"10.1111\/acel.70719","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:43:31Z","timestamp":1789191811000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rethinking Senescence Hallmarks in the Brain: Lessons From Peripheral Tissues and Challenges in Defining Neuronal Senescence"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1416-4113","authenticated-orcid":false,"given":"Miraj Ud Din","family":"Momand","sequence":"first","affiliation":[{"name":"Institute of Neuroimmunology Slovak Academy of Sciences  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0816-1572","authenticated-orcid":false,"given":"Kristina","family":"Macova","sequence":"additional","affiliation":[{"name":"Institute of Neuroimmunology Slovak Academy of Sciences  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6417-0370","authenticated-orcid":false,"given":"Dominika","family":"Fricova","sequence":"additional","affiliation":[{"name":"The Unit for Translational Research of Neurodegenerative Diseases, 2nd Department of Neurology, Faculty of Medicine Comenius University  Bratislava Slovakia"},{"name":"Institute of Histology and Embryology, Faculty of Medicine Comenius University  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.05.006"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14860"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16932"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI95145"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10600"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045069"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2010.06.021"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2020.07.002"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0543-y"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183653"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2233"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2026.1805691"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf6659"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12029"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.12.092"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2014.09.018"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-121808-102144"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq160"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2016.00208"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.70048"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00586-3"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-021-00142-3"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.881706"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-024-00429-0"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028035"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2014.02.010"},{"issue":"16","key":"e_1_2_10_28_1","first-page":"4854","article-title":"A P53\u2010Dependent, Telomere\u2010Independent Proliferative Life Span Barrier in Human Astrocytes Consistent With the Molecular Genetics of Glioma Development","volume":"63","author":"Evans R. 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