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Peer-reviewedCC BYNature Aging

Network-driven discovery of repurposable drugs targeting hallmarks of aging

  • Bnaya Gross1,2,3
  • Joseph Ehlert1,2,3
  • Vadim N. Gladyshev4,5
  • Joseph Loscalzo4,5
  • Albert-Ĺaszló Barabási6,7,8,3
8 affiliations
  1. 1Department of Physics, Northeastern University, Boston, MA, USA
  2. 2Network Science Institute, Northeastern University, Boston, MA, USA
  3. 3Department of Physics, Northeastern University, Boston, MA 02115
  4. 4Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
  5. 5Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
  6. 6Department of Network and Data Science, Central European University, Vienna, Austria. [email protected]
  7. 7Department of Physics, Northeastern University, Boston, MA, USA. [email protected]
  8. 8Network Science Institute, Northeastern University, Boston, MA, USA. [email protected]
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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.

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Cite

BibTeXRIS
BibTeX
@article{gross2026networkdriven,
  title = {{Network-driven discovery of repurposable drugs targeting hallmarks of aging}},
  author = {Bnaya Gross and Joseph Ehlert and Vadim N. Gladyshev and Joseph Loscalzo and Albert-Ĺaszló Barabási},
  journal = {Nature Aging},
  year = {2026},
  month = jun,
  doi = {10.1038/s43587-026-01161-8},
  url = {https://doi.org/10.1038/s43587-026-01161-8},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Network-driven discovery of repurposable drugs targeting hallmarks of aging
AU  - Bnaya Gross
AU  - Joseph Ehlert
AU  - Vadim N. Gladyshev
AU  - Joseph Loscalzo
AU  - Albert-Ĺaszló Barabási
PY  - 2026
DA  - 2026/06/26
JO  - Nature Aging
DO  - 10.1038/s43587-026-01161-8
UR  - https://doi.org/10.1038/s43587-026-01161-8
AB  - 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.
SN  - 2662-8465
ER  -