{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:27:03Z","timestamp":1792798023235,"version":"4.5.0"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03kk0s825","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the International Society for Neurochemistry"},{"id":[{"id":"https:\/\/ror.org\/050qa2043","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Instituto de Educa\u00e7\u00e3o M\u00e9dica"},{"id":[{"id":"https:\/\/ror.org\/04rs3t968","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Astrocyte senescence is a recognized feature of brain aging, but its impact on neuronal mitochondrial homeostasis remains poorly defined, particularly in human cells. Here we show that doxorubicin-induced senescence disrupts mitochondrial function in primary human astrocytes and compromises their capacity to sustain neuronal bioenergetics. Senescent astrocytes accumulated a denser population of smaller, ultrastructurally damaged mitochondria together with increased levels of fission, fusion and biogenesis-associated proteins. Despite this apparent expansion of the mitochondrial compartment, these cells displayed reduced mitochondrial membrane potential, intracellular ATP and cellular metabolic activity, indicating accumulation of a functionally impaired mitochondrial population. Senescence also remodeled the extracellular mitochondrial compartment: conditioned medium from senescent astrocytes contained fewer mitochondrial particles with lower membrane potential and reduced ATP. Functionally, conditioned medium from control astrocytes increased TOMM20 and PGC-1\u03b1 levels in human postmitotic neurons, whereas medium from senescent astrocytes failed to elicit this response and instead promoted hydrogen peroxide accumulation, ATP depletion and reduced cellular metabolic activity in the absence of overt cytotoxicity. Neurons acquired an astrocyte-derived MitoTracker signal from both conditions. Our data indicate that factors released by senescent human astrocytes are sufficient to induce neuronal mitochondrial and redox dysfunction.<\/jats:p>","DOI":"10.3390\/antiox15091127","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:07:06Z","timestamp":1788768426000},"page":"1127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Astrocyte Senescence Disrupts the Extracellular Mitochondrial Compartment and Compromises Bioenergetic Support to Human Neurons"],"prefix":"10.3390","volume":"15","author":[{"given":"Pedro","family":"Amorim","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00e3o Metab\u00f3lica Associada ao Envelhecimento, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, 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