{
  "abstract": "The antagonistic pleiotropy theory of aging predicts genetic trade-offs between early-life and late-life fitness. However, empirical evidence for such trade-offs in vertebrates remains scarce, particularly from causal genetic experiments. Here, combining genetic perturbation with longitudinal phenotyping in the turquoise killifish (Nothobranchius furzeri), we identify vestigial-like 3 (vgll3), previously linked by GWAS to age at maturity in humans and male Atlantic salmon, as a gene with antagonistically pleiotropic effects. Selective disruption of vgll3 isoforms accelerates male growth and maturation in a dose-dependent manner. Transcriptomic and cellular analyses indicated increased cell division, corroborated in vivo by elevated germline and intestinal stem-cell proliferation. However, early-life maturation incurs a late-life cost, linked to altered DNA damage response. Older mutant males develop melanoma-like tumors, validated via transplantation into immunodeficient rag2 models, and exhibit a shortened lifespan. Thus, we identify vgll3 as a key regulator of life-history variation with antagonistic effects across ages, balancing early-life fitness against late-life mortality.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Genetics, The Silberman Institute, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel",
    "Department of Obstetrics & Gynecology, Shaare Zedek Medical Center and Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel",
    "Department of Zoology, University of Cambridge, Cambridge, UK",
    "School of Biological Sciences, University of East Anglia, Norwich, UK",
    "University of South Bohemia in Ceske Budejovice, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Vodnany, Czech Republic",
    "Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel",
    "Department of Genetics, The Silberman Institute, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel. itamarh@mail.huji.ac.il"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Eitan Moses",
      "orcid": "0000-0003-0090-335X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Marva Bergman",
      "orcid": "0000-0002-8970-7402"
    },
    {
      "affs": [
        0
      ],
      "name": "Tehila Atlan",
      "orcid": "0000-0001-6836-7659"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Elizabeth Duxbury",
      "orcid": "0000-0002-5733-3645"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Roman Franěk",
      "orcid": "0000-0002-3464-1872"
    },
    {
      "affs": [
        0
      ],
      "name": "Omer Ben Dor"
    },
    {
      "affs": [
        0
      ],
      "name": "Henrik von Chrzanowski"
    },
    {
      "affs": [
        5
      ],
      "name": "Enas R. Abu‐Zhayia"
    },
    {
      "affs": [
        5
      ],
      "name": "Nabieh Ayoub",
      "orcid": "0000-0002-9549-9929"
    },
    {
      "affs": [
        0
      ],
      "name": "Shay Kinreich"
    },
    {
      "affs": [
        1
      ],
      "name": "Ido Ben‐Ami",
      "orcid": "0000-0003-1506-6670"
    },
    {
      "affs": [
        3
      ],
      "name": "Alexei A. Maklakov",
      "orcid": "0000-0002-5809-1203"
    },
    {
      "affs": [
        6
      ],
      "name": "Itamar Harel",
      "orcid": "0000-0001-9749-8279"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/daehbgps0d833.bib",
  "cited_by": 14,
  "doi": "10.1038/s41467-026-72381-0",
  "fulltext_url": null,
  "id": "daehbgps0d833",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-72381-0",
  "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",
      "1302|Genetics, Aging, and Longevity in Model Organisms"
    ]
  ],
  "openalex": "W7163207014",
  "pdf_url": null,
  "pmcid": "PMC13230779",
  "pmid": "42230577",
  "published": "2026-06-02",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/daehbgps0d833.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T13:20:46Z",
      "native_id": "W7163207014",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-72381-0"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1302|Genetics, Aging, and Longevity in Model Organisms",
      "subfield": "cell-biology"
    }
  ],
  "title": "An antagonistically pleiotropic gene regulates vertebrate growth, maturity, and lifespan",
  "title_text": "An antagonistically pleiotropic gene regulates vertebrate growth, maturity, and lifespan",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T13:20:46Z",
  "url": "https://research.draconitic.com/paper/daehbgps0d833",
  "venue": "Nature Communications",
  "versions": []
}