{
  "abstract": "Recent experimental evidence suggests that aging may arise from the progressive deterioration of the epigenetic landscape, while reversing the trend can result in cell and tissue rejuvenation. A mechanistic understanding of how restoration of a key component of this landscape - the 3D structure of the genome - can be accomplished is lacking. Here we investigate the lamina-dependent disruption and recovery of the 3D architecture of the Drosophila melanogaster genome at topologically associating domains (TADs) resolution ([~] 100 kb), using a model of the entire nucleus; weakening of chromatin-lamina interactions mimics a loss of chromatin organization associated with aging. We characterize this loss using the Shannon entropy of the appropriately normalized Hi-C contact and by deterioration of the chromosome territories. Our main finding is that increase in Hi-C map disorder and deterioration of chromosome territories induced by lamina depletion are largely reversible when the wild-type (WT)-like Lamina-associated domain (LAD)- nuclear-envelope interactions are restored; the original and recovered conformational states of chromatin are essentially indistinguishable by the bulk Hi-C contact matrix, and the recovered WT state of chromatin remains stable. The recovery is robust: we find that the WT-like 3D architecture can also be recovered from a more severely perturbed lamina-depleted and compartment-disrupted state, in which all attractive interactions have been switched off. The direct experimentally testable prediction is that the restoration of functional LAD- lamina interactions will promote recovery of the WT-like 3D chromatin architecture after lamina-dependent architectural disruption. We further hypothesize that lamin restoration may increase lifespan of the fruit fly and improve other aging-associated phenotypes through the recovery of young-like LAD- lamina attachments.",
  "abstract_shown": true,
  "affiliations": [
    "Virginia Tech"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "A. V. Onufriev"
    },
    {
      "name": "J. Zhang"
    },
    {
      "name": "I. V. Sharakhov"
    },
    {
      "name": "I. S. Tolokh"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4xbxpmbah8tn0.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.07.16.739007",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.07.16.739007v2.full",
  "id": "4xbxpmbah8tn0",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.07.16.739007v2",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genomics"
    ],
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7170053439",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.07.16.739007v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4xbxpmbah8tn0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:38Z",
      "native_id": "10.64898/2026.07.16.739007",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.07.16.739007v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Reversing aging-like 3D genome disorganization in a Drosophila interphase model",
  "title_text": "Reversing aging-like 3D genome disorganization in a Drosophila interphase model",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:38Z",
  "url": "https://research.draconitic.com/paper/4xbxpmbah8tn0",
  "venue": "bioRxiv",
  "versions": []
}