{
  "abstract": "Throughout life, somatic cells must preserve their identity while retaining the capacity to adapt. How this balance shifts with ageing and rejuvenation remains unclear. Here we identify miR-29 as a central point of convergence between the transcriptional programmes of physiological ageing and two routes to rejuvenation: induced reprogramming and the natural reset of early development. miR-29 rises with ageing, falls in both rejuvenation settings and shows the most conserved age-associated increase across vertebrates. miR-29 inhibition opposes transcriptional ageing, whereas mimics promote an older transcriptional state. Methylome analysis reveals a broader function: inhibition releases the miR-29 brake on remodelling, and mimic treatment reinforces it. This release increases methylation at repeat-associated CpGs and lowers epigenetic-clock estimates through unequal contributions in opposite directions. Inhibition also amplifies stimulus-induced methylation changes but reduces fidelity to lineage-specific methylation patterns. We extend this relationship to cancer, where low miR-29 expression marks tumours with younger epigenetic-age estimates yet greater methylation divergence from their tissue of origin. These findings identify miR-29 as a control point linking ageing, rejuvenation and cancer, and support a maladaptive trade-off model in which epigenetic fidelity is preserved at the expense of the plasticity needed for methylome maintenance and adaptation.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Oncology Research (IOR)"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "I. Craparotta"
    },
    {
      "name": "M. C. Barbera"
    },
    {
      "name": "G. A. Cassanmagnago"
    },
    {
      "name": "A. C. Salvatore"
    },
    {
      "name": "A. Sallemi"
    },
    {
      "name": "L. Guarrera"
    },
    {
      "name": "A. Vallerga"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Bolis"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ep9y6mgxd9j3y.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.18.759616",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.18.759616v1.full",
  "id": "ep9y6mgxd9j3y",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.18.759616v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "1312|Epigenetics and DNA Methylation"
    ]
  ],
  "openalex": "W7223294546",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.18.759616v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ep9y6mgxd9j3y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:18Z",
      "native_id": "10.64898/2026.10.18.759616",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.18.759616v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Age-driven miR-29 trades youthful plasticity for epigenetic fidelity",
  "title_text": "Age-driven miR-29 trades youthful plasticity for epigenetic fidelity",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:18Z",
  "url": "https://research.draconitic.com/paper/ep9y6mgxd9j3y",
  "venue": "bioRxiv",
  "versions": []
}