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Peer-reviewedCC BYScience Advances

Predicting and finding geroprotective compounds through modulating conserved longevity–associated aging modules

  • Weihan Huai1,2,3
  • Li-Fang Ng1,4
  • Jasinda H. Lee2,3
  • Qingyun Wang1,2,3
  • Kamil Pabis1,2,3
  • Zhuangli Yee1
  • Shivaanisha Raventhiran2,3
  • Shou-Ping Guan1,2,3
  • Shermaine Thein1,2,3
  • Stephen Dinesh Raj1,2,3
  • Jerald Tan1,4
  • Angelica Faye Ga1,4
7 more authors
  • Sharah Mae Capinpin2,3
  • Diogo Barardo1,2
  • Qing Zhang1,2,3
  • Zongmin Liu1,2,3
  • Esther Wong2,3,5
  • Brian Keith Kennedy1,2,3,5
  • Jan Gruber1,2,3,4
5 affiliations
  1. 1Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.
  2. 2Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore.
  3. 3Centre for Healthy Longevity, National University Health System, Singapore 159964, Singapore.
  4. 4Science Divisions, Yale, NUS College, Singapore 138527, Singapore.
  5. 5Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore.
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Abstract

Currently, no generalizable tools exist for predicting the impact of interventions on aging using gene expression changes. Here, we build a model for predicting potential geroprotectors by deconstructing the aging transcriptome into coexpression modules and identifying those modulated by life span–extending interventions in Caenorhabditis elegans ( C. elegans ). Many of these modules exhibited adaptive changes during aging that are linked to longevity. Using these longevity-associated modules, we predicted and validated 10 compounds (7 previously unreported) that significantly extended life span in C. elegans . RNA sequencing analysis of two top candidates also showed targeted modulation of our longevity-associated modules. We identified conservation of several modules in mice that were also correlated with frailty. Together, our findings demonstrate that beneficial transcriptomic adaptations occur during aging and that targeting longevity-associated modules offers a framework for geroprotector discovery.

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Cite

BibTeXRIS
BibTeX
@article{huai2026predicting,
  title = {{Predicting and finding geroprotective compounds through modulating conserved longevity–associated aging modules}},
  author = {Weihan Huai and Li-Fang Ng and Jasinda H. Lee and Qingyun Wang and Kamil Pabis and Zhuangli Yee and Shivaanisha Raventhiran and Shou-Ping Guan and Shermaine Thein and Stephen Dinesh Raj and Jerald Tan and Angelica Faye Ga and Sharah Mae Capinpin and Diogo Barardo and Qing Zhang and Zongmin Liu and Esther Wong and Brian Keith Kennedy and Jan Gruber},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aee3657},
  url = {https://www.science.org/doi/10.1126/sciadv.aee3657},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Predicting and finding geroprotective compounds through modulating conserved longevity–associated aging modules
AU  - Weihan Huai
AU  - Li-Fang Ng
AU  - Jasinda H. Lee
AU  - Qingyun Wang
AU  - Kamil Pabis
AU  - Zhuangli Yee
AU  - Shivaanisha Raventhiran
AU  - Shou-Ping Guan
AU  - Shermaine Thein
AU  - Stephen Dinesh Raj
AU  - Jerald Tan
AU  - Angelica Faye Ga
AU  - Sharah Mae Capinpin
AU  - Diogo Barardo
AU  - Qing Zhang
AU  - Zongmin Liu
AU  - Esther Wong
AU  - Brian Keith Kennedy
AU  - Jan Gruber
PY  - 2026
DA  - 2026/10/02
JO  - Science Advances
DO  - 10.1126/sciadv.aee3657
UR  - https://www.science.org/doi/10.1126/sciadv.aee3657
AB  - Currently, no generalizable tools exist for predicting the impact of interventions on aging using gene expression changes. Here, we build a model for predicting potential geroprotectors by deconstructing the aging transcriptome into coexpression modules and identifying those modulated by life span–extending interventions in Caenorhabditis elegans ( C. elegans ). Many of these modules exhibited adaptive changes during aging that are linked to longevity. Using these longevity-associated modules, we predicted and validated 10 compounds (7 previously unreported) that significantly extended life span in C. elegans . RNA sequencing analysis of two top candidates also showed targeted modulation of our longevity-associated modules. We identified conservation of several modules in mice that were also correlated with frailty. Together, our findings demonstrate that beneficial transcriptomic adaptations occur during aging and that targeting longevity-associated modules offers a framework for geroprotector discovery.
SN  - 2375-2548
ER  -