{
  "abstract": "Despite the thousands of genes implicated in age-related phenotypes, effective interventions for aging remain elusive, due to the multifactorial nature of longevity and the interconnectedness of molecular components involved. Here we introduce a network medicine framework to map 2,358 longevity-associated genes onto the human interactome to identify drug-repurposing candidates capable of modulating specific hallmarks of aging. We find that genes associated with each hallmark form a connected subgraph, or hallmark module, allowing us to measure the network proximity of 6,442 compounds to each hallmark. We then introduce a transcription-based metric, pAGE, which evaluates whether drug-induced expression shifts reinforce or counteract known age-related expression changes within each hallmark module. By integrating network proximity and pAGE, we identify drug-repurposing candidates targeting specific hallmarks and provide a falsifiable framework to leverage genomic discoveries for accelerating drug repurposing in longevity. Our findings are interpretable, revealing molecular mechanisms through which drugs modulate hallmarks.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Physics, Northeastern University, Boston, MA, USA",
    "Network Science Institute, Northeastern University, Boston, MA, USA",
    "Department of Physics, Northeastern University, Boston, MA 02115",
    "Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA",
    "Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115",
    "Department of Network and Data Science, Central European University, Vienna, Austria. barabasi@gmail.com",
    "Department of Physics, Northeastern University, Boston, MA, USA. barabasi@gmail.com",
    "Network Science Institute, Northeastern University, Boston, MA, USA. barabasi@gmail.com"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Bnaya Gross",
      "orcid": "0000-0003-1451-0290"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Joseph Ehlert"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Vadim N. Gladyshev",
      "orcid": "0000-0002-0372-7016"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Joseph Loscalzo",
      "orcid": "0000-0002-1153-8047"
    },
    {
      "affs": [
        5,
        6,
        7,
        2
      ],
      "name": "Albert-Ĺaszló Barabási",
      "orcid": "0000-0002-4028-3522"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0r2xzhptddjtj.bib",
  "cited_by": 8,
  "doi": "10.1038/s43587-026-01161-8",
  "fulltext_url": null,
  "id": "0r2xzhptddjtj",
  "issns": [
    "2662-8465"
  ],
  "landing_url": "https://doi.org/10.1038/s43587-026-01161-8",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "3002|Computational Drug Discovery Methods"
    ]
  ],
  "openalex": "W4414168900",
  "pdf_url": "https://www.nature.com/articles/s43587-026-01161-8.pdf",
  "pmcid": "PMC12425021",
  "pmid": "40949755",
  "published": "2026-06-26",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/0r2xzhptddjtj.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T13:21:00Z",
      "native_id": "W4414168900",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s43587-026-01161-8"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:3002|Computational Drug Discovery Methods",
      "subfield": "medicinal"
    }
  ],
  "title": "Network-driven discovery of repurposable drugs targeting hallmarks of aging",
  "title_text": "Network-driven discovery of repurposable drugs targeting hallmarks of aging",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:17Z",
  "url": "https://research.draconitic.com/paper/0r2xzhptddjtj",
  "venue": "Nature Aging",
  "versions": []
}