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Chemical reprogramming ameliorates cellular hallmarks of aging and extends lifespan
Lucas Schoenfeldt1,2, Patrick T Paine1, Sara Picó1
1Department of Biomedical Sciences, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Vaud, Switzerland.
EMBO Molecular Medicine
|June 30, 2025
Summary
Chemical reprogramming reverses aging hallmarks in human cells and extends lifespan in C. elegans. This approach offers a promising path for therapeutic interventions targeting age-related decline.
Area of Science:
- Biogerontology
- Cellular and Molecular Biology
- Epigenetics
Background:
- Cellular reprogramming can reverse aging hallmarks, but transcription factor methods have limited translational applications.
- Chemical reprogramming offers an alternative in vitro, yet its anti-aging potential remains unexplored.
Purpose of the Study:
- To investigate the impact of chemical-induced partial reprogramming on aging hallmarks in human cells.
- To identify an optimized chemical combination for ameliorating aging phenotypes.
- To evaluate the in vivo efficacy of chemical reprogramming in extending lifespan and healthspan.
Main Methods:
- Chemical-induced partial reprogramming of aged human cells.
- Assessment of aging drivers: genomic instability, epigenetic alterations, senescence, and oxidative stress.
- In vivo lifespan and healthspan studies in C. elegans.
Main Results:
- Chemical reprogramming improved genomic instability and epigenetic alterations in aged human cells.
- An optimized two-molecule combination ameliorated cellular senescence and oxidative stress.
- In vivo administration of the two-chemical combination significantly extended C. elegans lifespan and healthspan.
Conclusions:
- Chemical-induced partial reprogramming can reverse key aging drivers in human cells.
- This approach holds potential for therapeutic interventions to combat aging and extend lifespan.
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