{
  "abstract": "The human brain develops and matures over an exceptionally prolonged period of time that spans nearly two decades of life. Processes that govern species-specific aspects of human postnatal brain development are difficult to study in animal models1. While human brain organoids offer a promising in vitro model, they have thus far been shown to largely mimic early stages of brain development. Here we develop human brain organoids for 5 years in culture, optimizing growth conditions to extend excitatory neuron viability beyond previous limits. Using maturation-associated modules derived from endogenous human brain, we show that brain organoids transcriptionally age with cell type specificity over years in culture. Whole-genome methylation profiling reveals that the predicted epigenomic age of organoids correlates precisely with time spent in vitro, and parallels epigenomic ageing in vivo. Notably, we show that in chimeric organoids generated by mixing neural progenitors of different ages, old progenitors rapidly produce late neuronal fates, skipping the production of earlier neuronal progeny, therefore showing that progenitors that age in organoids retain a memory of the time spent in vitro. The data indicate that human brain organoids can continue to mature and record the passage of time over many years in culture. Human brain organoids were developed for over five years in culture to demonstrate that brain cells can continue to mature and record the passage of time, following human-specific endogenous programs, even outside the context of the organism.",
  "abstract_shown": true,
  "affiliations": [
    "Department for Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy",
    "Department of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA, USA",
    "Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA",
    "Department of Translational Neuroscience, University Medical Center Utrecht (UMCU), Brain Center, Utrecht University, Utrecht, The Netherlands",
    "Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany",
    "Digital Health Cluster, Hasso Plattner Institute for Digital Engineering, Digital Engineering Faculty, University of Potdsdam, Potsdam, Germany",
    "McGovern Institute, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA",
    "Department of Molecular and Cellular Biology and The Center for Brain Science, Harvard University, Cambridge, MA, USA",
    "Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA",
    "Genentech, San Francisco, CA, USA",
    "Broad Institute of MIT and Harvard, Boston, MA, USA",
    "Department of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA, USA. paola_arlotta@harvard.edu",
    "Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. paola_arlotta@harvard.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Irene Faravelli",
      "orcid": "0000-0001-8126-7353"
    },
    {
      "affs": [
        1,
        3,
        2
      ],
      "name": "Noelia Antón-Bolaños",
      "orcid": "0000-0001-6590-4316"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Anqi Wei",
      "orcid": "0000-0003-1617-8199"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Tyler Faits",
      "orcid": "0000-0002-7524-6166"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Abhishek Sampath Kumar",
      "orcid": "0000-0001-7918-6706"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Sophia Andreadis",
      "orcid": "0009-0008-6609-3402"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Rahel Kästli",
      "orcid": "0000-0002-3810-6228"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Marta Montero‐Crespo",
      "orcid": "0000-0002-7895-5961"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Mara Steiger",
      "orcid": "0000-0002-3747-685X"
    },
    {
      "affs": [
        6
      ],
      "name": "Daniel Leible",
      "orcid": "0009-0006-5491-6673"
    },
    {
      "affs": [
        6
      ],
      "name": "Enxi Zhang",
      "orcid": "0009-0006-8032-9421"
    },
    {
      "affs": [
        6
      ],
      "name": "Bobae An",
      "orcid": "0000-0002-6554-4186"
    },
    {
      "affs": [
        7
      ],
      "name": "Yaron Meirovitch",
      "orcid": "0000-0002-1946-8012"
    },
    {
      "affs": [
        1
      ],
      "name": "Sayara Silwal"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Sung Min Yang",
      "orcid": "0000-0003-4318-2011"
    },
    {
      "affs": [
        4
      ],
      "name": "Alexander Kovacsovics"
    },
    {
      "affs": [
        8,
        2
      ],
      "name": "Xian Adiconis",
      "orcid": "0000-0002-4052-2503"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Helene Kretzmer",
      "orcid": "0000-0002-0723-4980"
    },
    {
      "affs": [
        8,
        2
      ],
      "name": "Joshua Z. Levin",
      "orcid": "0000-0002-0170-3598"
    },
    {
      "affs": [
        6
      ],
      "name": "Edward S. Boyden",
      "orcid": "0000-0002-0419-3351"
    },
    {
      "affs": [
        7
      ],
      "name": "Jeff William Lichtman",
      "orcid": "0000-0002-0208-3212"
    },
    {
      "affs": [
        9,
        8
      ],
      "name": "Aviv Regev",
      "orcid": "0000-0003-3293-3158"
    },
    {
      "affs": [
        10,
        4
      ],
      "name": "Alexander Meissner",
      "orcid": "0000-0001-8646-7469"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Paola Arlotta",
      "orcid": "0000-0003-2184-2277"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fv3gqsgnpgw9c.bib",
  "cited_by": 26,
  "doi": "10.1038/s41586-026-10877-x",
  "fulltext_url": null,
  "id": "fv3gqsgnpgw9c",
  "issns": [
    "0028-0836",
    "1476-4687"
  ],
  "landing_url": "https://doi.org/10.1038/s41586-026-10877-x",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2806|Neurogenesis and neuroplasticity mechanisms"
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  "openalex": "W7203754433",
  "pdf_url": null,
  "pmcid": "PMC13581598",
  "pmid": "42618795",
  "published": "2026-08-19",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/fv3gqsgnpgw9c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:53Z",
      "native_id": "W7203754433",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41586-026-10877-x"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2806|Neurogenesis and neuroplasticity mechanisms",
      "subfield": "neuroscience"
    }
  ],
  "title": "Human brain organoids record the passage of time over multiple years",
  "title_text": "Human brain organoids record the passage of time over multiple years",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T13:20:36Z",
  "url": "https://research.draconitic.com/paper/fv3gqsgnpgw9c",
  "venue": "Nature",
  "versions": []
}